Preparation method of medicinal liquor and application of medicinal liquor in preparation of analgesic and anti-inflammatory products

Abstract

The application provides a preparation method of medicinal liquor and application of the medicinal liquor in preparation of analgesic and anti-inflammatory products, and relates to the technical field of medicines.Preparation method comprises the following steps: (1) crushing; (2) extraction; (3) standing and separation; (4) freezing and filtration, so that the medicinal liquor is obtained.In the preparation process, the medicinal liquor is obtained by adopting the steps of batch crushing, mixed extraction, standing, freezing and separating supernatant and suspension by different separation methods to extract traditional Chinese medicine ingredients.The medicinal liquor can better inhibit pain caused by heat stimulation and chemical substances, has better analgesic effect, can inhibit capillary permeability increase caused by acetic acid, has better anti-inflammatory effect, and has significant analgesic and anti-inflammatory effects.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to a method for preparing medicinal wine and its application in the preparation of analgesic and anti-inflammatory products. Background Technology

[0002] Pain is a comprehensive emotional experience encompassing the psychological sensations caused by actual or potential tissue damage, along with accompanying emotions such as frustration, irritability, and even despair. This unpleasant feeling can be fleeting or pervasive throughout the course of various diseases, becoming one of the most common clinical problems. Pain can be classified into acute pain and chronic pain based on its duration and nature.

[0003] Currently, the main treatments for pain include Western medicine and traditional Chinese medicine. Western medicine has significant advantages in pain management. Opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) are traditional analgesics widely used in clinical practice, and recent research has focused on overcoming their serious side effects. Through the development of dosage forms and improvements in administration methods, opioids have evolved from single intravenous and intramuscular administration to multiple forms and routes such as oral, sublingual, transdermal absorption, and spinal canal sustained release, prolonging the analgesic time and reducing side effects such as nausea, vomiting, and addiction. Although the development and updating of traditional analgesics are rapid, they still cannot overcome their inherent side effects, thus raising concerns about their clinical use. Traditional Chinese medicine has accumulated thousands of years of experience in treating pain, possessing unique efficacy and relatively few adverse reactions. In-depth exploration of traditional Chinese medicine compound formulas for treating pain has significant clinical value.

[0004] For example, Chinese patent CN116870076A discloses an anti-inflammatory and analgesic traditional Chinese medicine composition, its preparation method, and its application. The traditional Chinese medicine composition comprises the following components by mass percentage: 25-35% *Gynostemma pentaphyllum*, 10-20% *Taraxacum mongolicum*, 10-20% *Viola yedoensis*, 5-15% *Carthamus tinctorius*, 5-10% *Angelica sinensis*, 5-10% *Ligusticum chuanxiong*, 2-10% *Rehmannia glutinosa*, 2-10% *Centella asiatica*, and 1-3% natural borneol. This formula combines nine traditional Chinese medicinal materials, including *Gynostemma pentaphyllum*, dandelion, and Viola yedoensis, with appropriate combinations and synergistic effects, exhibiting good efficacy in reducing swelling and pain, promoting blood circulation and removing blood stasis, anti-inflammatory and antibacterial properties, and minimal toxic side effects.

[0005] For example, Chinese patent CN103536845A discloses the application of Jieyu Shugan capsules in the preparation of anti-inflammatory and analgesic drugs. This invention found that Jieyu Shugan capsules can significantly inhibit xylene-induced ear swelling in mice and acetic acid-induced increased peritoneal capillary permeability in mice; it also has a significant inhibitory effect on acetic acid-induced writhing response in mice and increases the thermal pain threshold in mice.

[0006] For example, Chinese patent CN114432362A discloses a traditional Chinese medicine composition, preparation, and application for analgesia, anti-inflammatory, and swelling-reducing effects. The raw materials of this invention's traditional Chinese medicine composition are clove, peppermint, and asarum. Clove has analgesic and anti-inflammatory properties; asarum has wind-dispelling, pain-relieving, and good anti-inflammatory effects; peppermint has cooling, antipruritic, anti-inflammatory, and analgesic effects, and also promotes penetration, resulting in good transdermal absorption. This invention mixes clove, asarum, and peppermint in a certain proportion, enhancing the anti-inflammatory, analgesic, and swelling-reducing effects. It is novel, highly effective, safe, and easily accepted by patients.

[0007] However, existing Chinese medicine compositions cannot effectively inhibit the increased capillary permeability in mice caused by acetic acid, i.e., they cannot effectively inhibit inflammatory exudation. Therefore, it is necessary to develop new uses for medicinal wines in enhancing analgesia and anti-inflammation. Summary of the Invention

[0008] Based on the shortcomings of existing technologies, this invention takes medicinal wine as its foundation and studies its preparation method. Through the study of its preparation method, the medicinal wine of this invention is obtained by extracting Chinese medicine components through batch crushing, mixing and extraction, standing, freezing and separation. It not only has good stability, does not separate into layers or produce sediment after long-term storage, but also has the effects of enhancing analgesia and anti-inflammation.

[0009] This invention is implemented as follows:

[0010] On one hand, the present invention provides a method for preparing medicinal wine, comprising the following steps:

[0011] (1) Crushing:

[0012] First, mix and grind the following ingredients: Amomum villosum, cinnamon, white cardamom, red cardamom, long pepper, and agarwood. Then add the following ingredients: prepared Polygonum multiflorum, Rehmannia glutinosa, Angelica dahurica, Dioscorea opposita, Galla chinensis, Pogostemon cablin, ginseng, Morus alba root bark, Erythrina variegata bark, Nardostachys chinensis, Angelica pubescens, Atractylodes lancea, Ligusticum chuanxiong, Cuscuta chinensis, Poria cocos, Citrus reticulata peel, Amomum tsao-ko, Cornus officinalis, Aconitum carmichaelii, Magnolia officinalis, Citrus reticulata peel, Schisandra chinensis, Achyranthes bidentata, Citrus aurantium, Alpinia officinarum, and Coltsfoot flower, fennel, platycodon root, prepared rehmannia root, acorus root, atractylodes rhizome, areca nut, licorice root, angelica root, gentian root, safflower, turmeric root, lotus seed, papaya, ophiopogon root, notopterygium root, cyperus rhizome, cistanche, astragalus root, asparagus root, peach kernel, gardenia fruit, alisma rhizome, lindera root, pinellia tuber, arisaema rhizome, bitter almond, poria cocos, polygala root, epimedium, sparganium rhizome, and madder root are mixed and pulverized to obtain a mixture.

[0013] (2) Extraction:

[0014] The liquor, red yeast rice, and other ingredients are mixed, heated to a boil, and then cooled to obtain a mixture.

[0015] (3) Settling and separation:

[0016] Take the medicine solution, seal it and let it stand. During the standing process, compressed air needs to be introduced and stirred. After the standing is completed, separate the supernatant and the suspension to obtain the medicine solution.

[0017] (4) Freezing and filtration:

[0018] The medicinal liquid is frozen and stored, and then filtered to obtain the medicinal wine.

[0019] Preferably, the particle size of the mixture in step (1) above is 24-50 mesh.

[0020] Preferably, in step (1) above, the yam is stir-fried yam; the Atractylodes lancea is stir-fried Atractylodes lancea; the Cuscuta chinensis is salt-fried Cuscuta chinensis; the Citrus reticulata peel is stir-fried Citrus reticulata peel; the Cornus officinalis is cornus officinalis without pit; the Aconitum carmichaelii is processed Aconitum carmichaelii; the Citrus aurantium is stir-fried Citrus aurantium; the fennel is salt-fried fennel; the Atractylodes macrocephala is stir-fried Atractylodes macrocephala; the lotus seed is lotus seed without heart; the Ophiopogon japonicus is Ophiopogon japonicus without heart; the Cyperus rotundus is stir-fried Cyperus rotundus; the Gardenia jasminoides is gardenia jasminoides stir-fried; the Pinellia ternata is processed Pinellia ternata; the Arisaema heterophyllum is processed Arisaema heterophyllum; the bitter almond is bitter almond with peel and tip removed; the Epimedium brevicornu is stir-fried Epimedium brevicornu; and the Sparganium stoloniferum is Sparganium stoloniferum processed with vinegar.

[0021] Preferably, the heating in step (2) above is steam heating, and the heating temperature is 75-85℃.

[0022] Preferably, the cooling temperature described in step (2) above is 25-30°C.

[0023] Preferably, the pressure of the compressed air in step (3) above is ≥0.40MPa.

[0024] Preferably, the settling time in step (3) above is more than 2 months. During the first 15 days of the settling process, compressed air needs to be introduced every day and the mixture needs to be stirred for 10-20 minutes.

[0025] Preferably, the step of separating the supernatant in step (3) above is to use a horizontal scraper centrifuge for separation, with a screen mesh of 80 mesh, a discharge speed of 4-6 r / min, a feed speed of 8-12 r / min, and a centrifugation speed of 40-44 r / min.

[0026] More preferably, the step of separating the supernatant in step (3) above is to use a horizontal scraper centrifuge for separation, with a screen mesh of 80 mesh, a discharge speed of 5 r / min, a feed speed of 10 r / min, and a centrifugation speed of 42 r / min.

[0027] Preferably, the step of separating the suspension in step (3) above is to use a horizontal screw discharge sedimentation turbine centrifuge for separation, with a drum speed of 2400-3000 r / min and a differential speed of 23-28 r / min.

[0028] Preferably, the step of separating the suspension in step (3) above is to use a horizontal screw discharge sedimentation turbine centrifuge for separation, with a drum speed of 2600 r / min and a differential speed of 25 r / min.

[0029] Preferably, the freezing temperature in step (4) above is ≤-3℃.

[0030] Preferably, the storage time described in step (4) above is 7-10 days.

[0031] Preferably, the filtration in step (4) above is carried out using a diatomaceous earth filter, with a pressure ≥0.1MPa after soil application and a final filtration pressure ≤0.35MPa.

[0032] Preferably, the medicinal wine contains the following components by weight: 60 parts Amomum villosum, 120 parts Cinnamomum cassia, 60 parts Amomum cardamomum, 30 parts Amomum villosum var. rubra, 60 parts Piper longum, 30 parts Aquilaria sinensis, 15 parts processed Polygonum multiflorum, 15 parts Rehmannia glutinosa, 15 parts Angelica dahurica, 15 parts Dioscorea opposita, 15 parts Galla chinensis, 15 parts Pogostemon cablin, 30 parts Ginseng, 15 parts Morus alba root bark, 15 parts Erythrina variegata bark, 15 parts Nardostachys jatamansi, 15 parts Angelica pubescens, 15 parts Atractylodes lancea, 15 parts Ligusticum chuanxiong, 15 parts Cuscuta chinensis, 15 parts Poria cocos, 15 parts Citrus reticulata peel, 15 parts Amomum tsao-ko, 15 parts Cornus officinalis, 15 parts Aconitum carmichaelii, 30 parts Magnolia officinalis, 15 parts Citrus reticulata peel, 15 parts Schisandra chinensis, 15 parts Achyranthes bidentata, 30 parts Citrus aurantium, and 30 parts Alpinia galanga. 15 parts of Kaempferia galanga, 15 parts of Tussilago farfara, 240 parts of Foeniculum vulgare, 60 parts of Platycodon grandiflorus, 30 parts of Rehmannia glutinosa, 30 parts of Acorus tatarinowii, 45 parts of Atractylodes macrocephala, 45 parts of Areca catechu, 30 parts of Glycyrrhiza uralensis, 90 parts of Angelica sinensis, 15 parts of Gentiana macrophylla, 60 parts of Carthamus tinctorius, 15 parts of Curcuma zedoaria, 15 parts of Nelumbo nucifera, 15 parts of Chaenomeles speciosa, 15 parts of Ophiopogon japonicus, 15 parts of Notopterygium incisum, 15 parts of Cyperus rotundus, 15 parts of Cistanche deserticola, 15 parts of Astragalus membranaceus, 15 parts of Asparagus cochinchinensis, 15 parts of Prunus persica, 15 parts of Gardenia jasminoides, 15 parts of Alisma plantago-aquatica, 15 parts of Lindera strychnifolia, 15 parts of Pinellia ternata, 15 parts of Arisaema heterophyllum, 15 parts of Prunus armeniaca, 30 parts of Poria cocos, 15 parts of Polygala tenuifolia, 15 parts of Epimedium brevicornu, 15 parts of Sparganium stoloniferum, 15 parts of Rubia cordifolia, 158,000 parts of Baijiu (Chinese white liquor), and 900 parts of red yeast rice.

[0033] The present invention also provides a medicinal wine prepared by the above method.

[0034] This invention also provides the application of the medicinal wine prepared by the above method in the preparation of analgesic and anti-inflammatory products.

[0035] Furthermore, the medication is a product capable of suppressing pain caused by heat stimulation.

[0036] Furthermore, the medication is a product capable of suppressing pain caused by chemical substances.

[0037] Furthermore, the drug is a product capable of inhibiting increased capillary permeability caused by acetic acid.

[0038] More preferably, the drug is a product that can inhibit pain caused by heat stimulation or chemical substances, and can inhibit increased capillary permeability caused by acetic acid.

[0039] Compared with the prior art, the present invention has the following beneficial effects:

[0040] 1. This invention studies the preparation method of a medicinal wine product. The preparation process involves batch pulverization, mixed extraction, settling, freezing, and using different separation methods to separate the supernatant and suspension to extract the medicinal components. This medicinal wine can better inhibit pain caused by heat stimulation and chemical substances, exhibiting a better analgesic effect; it can also inhibit the increase in capillary permeability caused by acetic acid, resulting in a better effect of inhibiting inflammatory exudation. The medicinal wine of this invention has significant analgesic and anti-inflammatory effects.

[0041] 2. This invention comprehensively utilizes the components of various extracts, and the combination is reasonable so that they can be absorbed efficiently to exert their effects; at the same time, through specific extracts and extraction methods, the effective components of the medicinal wine have high activity, significant analgesic and anti-inflammatory effects, and good stability. It does not separate into layers or produce sediment even after long-term storage.

[0042] This invention uses a horizontal scraper centrifuge to separate the supernatant. By controlling the screen mesh to 80 mesh, the discharge speed to 4-6 r / min, the feed speed to 8-12 r / min, and the centrifugation speed to 40-44 r / min, efficient and continuous solid-liquid separation is achieved.

[0043] This invention uses a horizontal screw discharge sedimentation turbine centrifuge to separate suspensions. With a drum rotation speed of 2400-3000 r / min and a differential speed of 23-28 r / min, solid-liquid separation can be better achieved, effectively improving the clarity of the liquid phase and reducing the water content of the solid phase.

[0044] In the implementation of this invention, the liquid medicine is frozen to a temperature of ≤-3℃ before filtration, which can effectively reduce the formation of precipitates in the liquid medicine and achieve efficient purification while retaining the effective ingredients.

[0045] The present invention achieves good stability in the medicinal wine through multiple centrifugation and filtration processes, and can maintain high clarity even after long-term storage. Detailed Implementation

[0046] The following non-limiting embodiments are intended to enable those skilled in the art to gain a more comprehensive understanding of the present invention, but do not limit the invention in any way. The following content is merely an exemplary description of the scope of protection claimed by the present invention, and those skilled in the art can make various changes and modifications to the present invention based on the disclosed content, and such changes should also fall within the scope of protection claimed by the present invention.

[0047] When numerical ranges are given in the embodiments, it should be understood that, unless otherwise stated in the invention, both endpoints of each numerical range and any value between the two endpoints may be selected. Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0048] The present invention will be further described below by way of specific embodiments. Unless otherwise specified, all chemical reagents used in the embodiments of the present invention are obtained through conventional commercial means.

[0049] In the following examples, “part” and “g” have the same meaning, that is, 1 part = 1g.

[0050] Example 1: A method for preparing a medicinal wine

[0051] The medicinal wine contains the following components by weight: Amomum villosum 60g, Cinnamomum cassia 120g, Amomum cardamomum 60g, Amomum villosum 30g, Piper longum 60g, Agarwood 30g, Prepared Polygonum multiflorum 15g, Rehmannia glutinosa 15g, Angelica dahurica 15g, Dioscorea opposita 15g, Galla chinensis 15g, Pogostemon cablin 15g, Ginseng 30g, Morus alba root bark 15g, Erythrina variegata bark 15g, Nardostachys jatamansi 15g, Angelica pubescens 15g, Atractylodes lancea 15g, Ligusticum chuanxiong 15g, Cuscuta chinensis 15g, Poria cocos 15g, Citrus reticulata peel 15g, Amomum tsao-ko 15g, Cornus officinalis 15g, Aconitum carmichaelii 15g, Magnolia officinalis 30g, Citrus reticulata peel 15g, Schisandra chinensis 15g, Achyranthes bidentata 15g, Citrus aurantium 30g, Alpinia officinarum 30g, Kaempferia galanga 15g. g, Coltsfoot Flower 15g, Fennel 240g, Platycodon 60g, Rehmannia glutinosa 30g, Acorus tatarinowii 30g, Atractylodes macrocephala 45g, Areca catechu 45g, Licorice 30g, Angelica sinensis 90g, Gentiana macrophylla 15g, Carthamus tinctorius 60g, Curcuma zedoaria 15g, Nelumbo nucifera 15g, Chaenomeles speciosa 15g, Ophiopogon japonicus 15g, Notopterygium incisum 15g, Cyperus rotundus 15g, Cistanche deserticola 15g, Astragalus membranaceus 15g, Asparagus cochinchinensis 15g, Prunus persica 15g, Gardenia jasminoides 15g, Alisma plantago-aquatica 15g, Lindera strychnifolia 15g, Pinellia ternata 15g, Arisaema heterophyllum 15g, Prunus armeniaca 15g, Poria cocos 30g, Polygala tenuifolia 15g, Epimedium brevicornu 15g, Sparganium stoloniferum 15g, Rubia cordifolia 15g, Baijiu (Chinese white liquor) 158kg and Red yeast rice 0.9kg.

[0052] The preparation method is as follows:

[0053] (1) Crushing:

[0054] First, mix and grind the following ingredients: Amomum villosum, cinnamon, white cardamom, red cardamom, long pepper, and agarwood. Then add the following ingredients: prepared Polygonum multiflorum, Rehmannia glutinosa, Angelica dahurica, Dioscorea opposita, Galla chinensis, Pogostemon cablin, ginseng, Morus alba root bark, Erythrina variegata bark, Nardostachys chinensis, Angelica pubescens, Atractylodes lancea, Ligusticum chuanxiong, Cuscuta chinensis, Poria cocos, Citrus reticulata peel, Amomum tsao-ko, Cornus officinalis, Aconitum carmichaelii, Magnolia officinalis, Citrus reticulata peel, Schisandra chinensis, Achyranthes bidentata, Citrus aurantium, Alpinia officinarum, Kaempferia galanga, and Tussilago farfara. Fennel, Platycodon grandiflorus, Rehmannia glutinosa, Acorus tatarinowii, Atractylodes macrocephala, Areca catechu, Glycyrrhiza uralensis, Angelica sinensis, Gentiana macrophylla, Carthamus tinctorius, Curcuma zedoaria, Nelumbo nucifera, Chaenomeles speciosa, Ophiopogon japonicus, Notopterygium incisum, Cyperus rotundus, Cistanche deserticola, Astragalus membranaceus, Asparagus cochinchinensis, Prunus persica, Gardenia jasminoides, Alisma plantago-aquatica, Lindera strychnifolia, Pinellia ternata, Arisaema heterophyllum, Prunus armeniaca, Poria cocos, Polygala tenuifolia, Epimedium brevicornu, Sparganium stoloniferum, and Rubia cord

[0055] (2) Extraction:

[0056] The mixture of baijiu (Chinese liquor), red yeast rice, and other ingredients is heated to 80°C and boiled, then cooled to 30°C to obtain a mixed liquid.

[0057] (3) Settling and separation:

[0058] The liquid medicine was sealed and allowed to stand for more than 2 months. During the first 15 days of the standing process, compressed air with a pressure of ≥0.40MPa was introduced daily and the mixture was stirred for 10 minutes. After the standing period, a horizontal scraper centrifuge was used for separation. The screen mesh was 80 mesh, the discharge speed was 4 r / min, the feed speed was 8 r / min, and the centrifugation speed was 40 r / min to separate the supernatant. A horizontal screw discharge sedimentation turbine centrifuge was used for separation. The drum speed was 2400 r / min and the differential speed was 23 r / min to separate the suspension and obtain the liquid medicine.

[0059] (4) Freezing and filtration:

[0060] The medicinal liquid is frozen to a temperature of ≤-3℃ and stored for 7 days. Then it is filtered using a diatomaceous earth filter. The pressure after applying the diatomaceous earth is ≥0.1MPa, and the final filtration pressure is ≤0.35MPa. If the pressure exceeds 0.35MPa, it needs to be cleaned and filtered again after applying the diatomaceous earth to obtain the medicinal wine.

[0061] Example 2: A method for preparing a medicinal wine

[0062] The medicinal wine contains the following components by weight: Amomum villosum 60g, Cinnamomum cassia 120g, Amomum cardamomum 60g, Amomum villosum 30g, Piper longum 60g, Agarwood 30g, Prepared Polygonum multiflorum 15g, Rehmannia glutinosa 15g, Angelica dahurica 15g, Dioscorea opposita 15g, Galla chinensis 15g, Pogostemon cablin 15g, Ginseng 30g, Morus alba root bark 15g, Erythrina variegata bark 15g, Nardostachys jatamansi 15g, Angelica pubescens 15g, Atractylodes lancea 15g, Ligusticum chuanxiong 15g, Cuscuta chinensis 15g, Poria cocos 15g, Citrus reticulata peel 15g, Amomum tsao-ko 15g, Cornus officinalis 15g, Aconitum carmichaelii 15g, Magnolia officinalis 30g, Citrus reticulata peel 15g, Schisandra chinensis 15g, Achyranthes bidentata 15g, Citrus aurantium 30g, Alpinia officinarum 30g, Kaempferia galanga 15g. g, Coltsfoot Flower 15g, Fennel 240g, Platycodon 60g, Rehmannia glutinosa 30g, Acorus tatarinowii 30g, Atractylodes macrocephala 45g, Areca catechu 45g, Licorice 30g, Angelica sinensis 90g, Gentiana macrophylla 15g, Carthamus tinctorius 60g, Curcuma zedoaria 15g, Nelumbo nucifera 15g, Chaenomeles speciosa 15g, Ophiopogon japonicus 15g, Notopterygium incisum 15g, Cyperus rotundus 15g, Cistanche deserticola 15g, Astragalus membranaceus 15g, Asparagus cochinchinensis 15g, Prunus persica 15g, Gardenia jasminoides 15g, Alisma plantago-aquatica 15g, Lindera strychnifolia 15g, Pinellia ternata 15g, Arisaema heterophyllum 15g, Prunus armeniaca 15g, Poria cocos 30g, Polygala tenuifolia 15g, Epimedium brevicornu 15g, Sparganium stoloniferum 15g, Rubia cordifolia 15g, Baijiu (Chinese white liquor) 158kg and Red yeast rice 0.9kg.

[0063] The preparation method is as follows:

[0064] (1) Crushing:

[0065] First, mix and grind the following ingredients: Amomum villosum, cinnamon, white cardamom, red cardamom, long pepper, and agarwood. Then add the following ingredients: prepared Polygonum multiflorum, Rehmannia glutinosa, Angelica dahurica, Dioscorea opposita, Galla chinensis, Pogostemon cablin, ginseng, Morus alba root bark, Erythrina variegata bark, Nardostachys chinensis, Angelica pubescens, Atractylodes lancea, Ligusticum chuanxiong, Cuscuta chinensis, Poria cocos, Citrus reticulata peel, Amomum tsao-ko, Cornus officinalis, Aconitum carmichaelii, Magnolia officinalis, Citrus reticulata peel, Schisandra chinensis, Achyranthes bidentata, Citrus aurantium, Alpinia officinarum, Kaempferia galanga, and Tussilago farfara. Fennel, Platycodon grandiflorus, Rehmannia glutinosa, Acorus tatarinowii, Atractylodes macrocephala, Areca catechu, Glycyrrhiza uralensis, Angelica sinensis, Gentiana macrophylla, Carthamus tinctorius, Curcuma zedoaria, Nelumbo nucifera, Chaenomeles speciosa, Ophiopogon japonicus, Notopterygium incisum, Cyperus rotundus, Cistanche deserticola, Astragalus membranaceus, Asparagus cochinchinensis, Prunus persica, Gardenia jasminoides, Alisma plantago-aquatica, Lindera strychnifolia, Pinellia ternata, Arisaema heterophyllum, Prunus armeniaca, Poria cocos, Polygala tenuifolia, Epimedium brevicornu, Sparganium stoloniferum, and Rubia cord

[0066] (2) Extraction:

[0067] The mixture of baijiu (Chinese liquor), red yeast rice, and other ingredients is heated to 80°C and boiled, then cooled to 30°C to obtain a mixed liquid.

[0068] (3) Settling and separation:

[0069] The liquid medicine was sealed and allowed to stand for more than 2 months. During the first 15 days of the standing process, compressed air with a pressure of ≥0.40MPa was introduced daily and the mixture was stirred for 10 minutes. After the standing period, a horizontal scraper centrifuge was used for separation. The screen mesh was 80 mesh, the discharge speed was 6 r / min, the feed speed was 12 r / min, and the centrifugation speed was 44 r / min to separate the supernatant. A horizontal screw discharge sedimentation turbine centrifuge was used for separation. The drum speed was 3000 r / min and the differential speed was 28 r / min to separate the suspension and obtain the liquid medicine.

[0070] (4) Freezing and filtration:

[0071] The medicinal liquid is frozen to a temperature of ≤-3℃ and stored for 10 days. Then it is filtered using a diatomaceous earth filter. The pressure after applying the diatomaceous earth is ≥0.1MPa, and the final filtration pressure is ≤0.35MPa. If the pressure exceeds 0.35MPa, it needs to be cleaned and filtered again after applying the diatomaceous earth to obtain the medicinal wine.

[0072] Example 3: A method for preparing a medicinal wine

[0073] The medicinal wine contains the following components by weight: Amomum villosum 60g, Cinnamomum cassia 120g, Amomum cardamomum 60g, Amomum villosum 30g, Piper longum 60g, Agarwood 30g, Prepared Polygonum multiflorum 15g, Rehmannia glutinosa 15g, Angelica dahurica 15g, Dioscorea opposita 15g, Galla chinensis 15g, Pogostemon cablin 15g, Ginseng 30g, Morus alba root bark 15g, Erythrina variegata bark 15g, Nardostachys jatamansi 15g, Angelica pubescens 15g, Atractylodes lancea 15g, Ligusticum chuanxiong 15g, Cuscuta chinensis 15g, Poria cocos 15g, Citrus reticulata peel 15g, Amomum tsao-ko 15g, Cornus officinalis 15g, Aconitum carmichaelii 15g, Magnolia officinalis 30g, Citrus reticulata peel 15g, Schisandra chinensis 15g, Achyranthes bidentata 15g, Citrus aurantium 30g, Alpinia officinarum 30g, Kaempferia galanga 15g. g, Coltsfoot Flower 15g, Fennel 240g, Platycodon 60g, Rehmannia glutinosa 30g, Acorus tatarinowii 30g, Atractylodes macrocephala 45g, Areca catechu 45g, Licorice 30g, Angelica sinensis 90g, Gentiana macrophylla 15g, Carthamus tinctorius 60g, Curcuma zedoaria 15g, Nelumbo nucifera 15g, Chaenomeles speciosa 15g, Ophiopogon japonicus 15g, Notopterygium incisum 15g, Cyperus rotundus 15g, Cistanche deserticola 15g, Astragalus membranaceus 15g, Asparagus cochinchinensis 15g, Prunus persica 15g, Gardenia jasminoides 15g, Alisma plantago-aquatica 15g, Lindera strychnifolia 15g, Pinellia ternata 15g, Arisaema heterophyllum 15g, Prunus armeniaca 15g, Poria cocos 30g, Polygala tenuifolia 15g, Epimedium brevicornu 15g, Sparganium stoloniferum 15g, Rubia cordifolia 15g, Baijiu (Chinese white liquor) 158kg and Red yeast rice 0.9kg.

[0074] The preparation method is as follows:

[0075] (1) Crushing:

[0076] First, mix and grind the following ingredients: Amomum villosum, cinnamon, white cardamom, red cardamom, long pepper, and agarwood. Then add the following ingredients: prepared Polygonum multiflorum, Rehmannia glutinosa, Angelica dahurica, Dioscorea opposita, Galla chinensis, Pogostemon cablin, ginseng, Morus alba root bark, Erythrina variegata bark, Nardostachys chinensis, Angelica pubescens, Atractylodes lancea, Ligusticum chuanxiong, Cuscuta chinensis, Poria cocos, Citrus reticulata peel, Amomum tsao-ko, Cornus officinalis, Aconitum carmichaelii, Magnolia officinalis, Citrus reticulata peel, Schisandra chinensis, Achyranthes bidentata, Citrus aurantium, Alpinia officinarum, Kaempferia galanga, and Tussilago farfara. Fennel, Platycodon grandiflorus, Rehmannia glutinosa, Acorus tatarinowii, Atractylodes macrocephala, Areca catechu, Glycyrrhiza uralensis, Angelica sinensis, Gentiana macrophylla, Carthamus tinctorius, Curcuma zedoaria, Nelumbo nucifera, Chaenomeles speciosa, Ophiopogon japonicus, Notopterygium incisum, Cyperus rotundus, Cistanche deserticola, Astragalus membranaceus, Asparagus cochinchinensis, Prunus persica, Gardenia jasminoides, Alisma plantago-aquatica, Lindera strychnifolia, Pinellia ternata, Arisaema heterophyllum, Prunus armeniaca, Poria cocos, Polygala tenuifolia, Epimedium brevicornu, Sparganium stoloniferum, and Rubia cord

[0077] (2) Extraction:

[0078] The mixture of baijiu (Chinese liquor), red yeast rice, and other ingredients is heated to 78°C and boiled, then cooled to 25°C to obtain a mixed liquid.

[0079] (3) Settling and separation:

[0080] The liquid medicine was sealed and allowed to stand for more than 2 months. During the first 15 days of the standing process, compressed air with a pressure of ≥0.40MPa was introduced daily and the mixture was stirred for 10 minutes. After the standing period, a horizontal scraper centrifuge was used for separation. The screen mesh was 80 mesh, the discharge speed was 5 r / min, the feed speed was 10 r / min, and the centrifugation speed was 42 r / min to separate the supernatant. A horizontal screw discharge sedimentation turbine centrifuge was used for separation. The drum speed was 2600 r / min and the differential speed was 25 r / min to separate the suspension and obtain the liquid medicine.

[0081] (4) Freezing and filtration:

[0082] The medicinal liquid is frozen to a temperature of ≤-3℃ and stored for 7 days. Then it is filtered using a diatomaceous earth filter. The pressure after applying the diatomaceous earth is ≥0.1MPa, and the final filtration pressure is ≤0.35MPa. If the pressure exceeds 0.35MPa, it needs to be cleaned and filtered again after applying the diatomaceous earth to obtain the medicinal wine.

[0083] Comparative Example 1: A method for preparing a medicinal wine

[0084] The product prepared by the method described in the examples of patent CN1192928A.

[0085] That is: Take Polygonum multiflorum, Rehmannia glutinosa, Angelica dahurica, Dioscorea opposita, Galla chinensis, Pogostemon cablin, Morus alba root bark, Erythrina variegata bark, Nardostachys chinensis, Angelica pubescens, Atractylodes lancea, Ligusticum chuanxiong, Cuscuta chinensis, Poria cocos, Citrus reticulata peel, Amomum tsao-ko, Cornus officinalis, Aconitum carmichaelii, Citrus reticulata peel, Schisandra chinensis, Achyranthes bidentata, Kaempferia galanga, Tussilago farfara, Gentiana macrophylla, Curcuma zedoaria, Nelumbo nucifera, Chaenomeles speciosa, Ophiopogon japonicus, Notopterygium incisum, Cyperus rotundus, Cistanche deserticola, Astragalus membranaceus, Asparagus cochinchinensis, Prunus persica, Gardenia jasminoides, Alisma plantago-aquatica, Lindera strychnifolia, Pinellia ternata, Arisaema heterophyllum, Prunus armeniaca, Polygala tenuifolia, Epimedium brevicornu, and three... 15g each of 44 herbs including Rhizoma Cyperi and Radix Rubiae; 30g each of 8 herbs including Radix Ginseng, Cortex Magnoliae Officinalis, Fructus Aurantii Immaturus, Radix Alpiniae Galangi, Radix Rehmanniae Praeparata, Rhizoma Acoruse Tatarinowii, Radix Glycyrrhizae, and Rhizoma Poriae; 45g each of Rhizoma Atractylodis Macrocephalae and Semen Arecae; 60g each of Radix Platycodi and Radix Carthami; 90g of Radix Angelicae Sinensis; 240g of Herba Eupatorii; 58 herbs in total are mixed and ground into powder. Then, 30g each of Fructus Amomi and Fructus Aquilariae; 60g each of Fructus Amomi, Fructus Amomi, and Fructus Piper Longi; and 120g of Fructus Cinnamomi; 6 herbs in total are mixed and ground into coarse powder.

[0086] Place 158 kg of baijiu (Chinese white liquor) and 0.9 kg of red yeast rice in a jar, then add the 64 pulverized Chinese medicinal herbs mentioned above. Cover the jar, heat it in a water bath until the liquor boils, pour it into a vat, cool it, seal it, and let it stand for more than two months. Take the supernatant, press the residue, clarify the extracted liquid, add 1 g of finely ground musk powder, stir well, seal and let it stand, combine it with the supernatant liquid, filter it, and you have the final product.

[0087] Comparative Example 2

[0088] The difference from Example 3 is that freezing was not performed; the centrifuged liquid was directly filtered. The other steps were the same as in Example 3, thus obtaining the medicinal wine.

[0089] Comparative Example 3

[0090] The difference from Example 3 is that after settling, only a horizontal scraper centrifuge is used for separation, with a screen mesh of 80 mesh, a discharge speed of 5 r / min, a feed speed of 10 r / min, and a centrifugation speed of 42 r / min to separate the mixture. The other operating steps are the same as in Example 3, thus obtaining the medicinal wine.

[0091] Comparative Example 4

[0092] The difference from Example 3 is that after settling, only a horizontal screw discharge sedimentation turbine centrifuge is used for separation. The drum speed is 2600 r / min and the differential speed is 25 r / min to separate the mixture. The other operating steps are the same as in Example 3, and the medicinal wine is obtained.

[0093] Comparative Example 5

[0094] The difference from Example 3 is as follows:

[0095] (3) Settling and separation:

[0096] The liquid medicine was sealed and allowed to stand for more than 2 months. During the first 15 days of the standing process, compressed air with a pressure of ≥0.40MPa was introduced daily and the mixture was stirred for 10 minutes. After the standing period, a horizontal scraper centrifuge was used for separation. The screen mesh was 80 mesh, the discharge speed was 8 r / min, the feed speed was 15 r / min, and the centrifugation speed was 50 r / min to separate the supernatant. A horizontal screw discharge sedimentation turbine centrifuge was used for separation. The drum speed was 2000 r / min and the differential speed was 20 r / min to separate the suspension and obtain the liquid medicine.

[0097] The other steps are the same as in Example 3, and the medicinal wine is obtained.

[0098] Effect Experiment

[0099] I. Stability Testing:

[0100] Experimental methods:

[0101] 1. Total solids content test:

[0102] Accurately measure 20 mL of the supernatant of the medicinal wine, place it in an evaporating dish dried to constant weight, evaporate it to dryness on a water bath, dry it at 105℃ for 3 hours, transfer it to a desiccator, cool it for 30 minutes, and quickly and accurately weigh it. A high and stable total solids content indicates that the content of the effective drug components in the medicinal wine is high and stable.

[0103] 2. Ethanol content: The content should be 36-38% according to the ethanol content determination method (General Rule 0711).

[0104] 3. The pH should be 4.5-5.5.

[0105] 4. Microbial limit test: The test shall be conducted in accordance with the Microbial Limit Test Method for Non-sterile Products in the Chinese Pharmacopoeia 2020 Edition.

[0106] 5. Identification: Thin-layer chromatography was used for detection.

[0107] The test results are shown in Table 1.

[0108] Table 1

[0109]

[0110] According to the test results in Table 1 above, the medicinal wines prepared in Examples 1-3 of this invention have better properties, namely, a deep reddish-brown color, a slightly sweet and slightly bitter taste, and still maintain high clarity after 36 months of storage, with no precipitation and a high content of effective ingredients, all above 3.0g / 20mL. Comparative Example 1, prepared using conventional methods without centrifugation or filtration, resulted in significantly reduced stability; after 18 months of storage, trace amounts of precipitation occurred, and after 36 months, a precipitate easily dispersed by gentle shaking formed. Furthermore, the solid content, i.e., the content of effective ingredients, decreased, indicating significantly reduced stability. Comparative Example 2 did not undergo freezing before filtration. The failure to remove precipitated components during processing also affected the stability of the medicinal wine. After 36 months of storage, trace amounts of precipitate formed, and the solid content, i.e., the content of active ingredients, decreased. In Comparative Examples 3 and 4, using only one filtration method or changing the filtration parameters also affected the stability of the medicinal wine. In both examples, trace amounts of precipitate formed after 24 months of storage, and the solid content, i.e., the content of active ingredients, decreased. In Comparative Example 5, changing the operating parameters during centrifugation also affected the stability of the medicinal wine to some extent, causing trace amounts of precipitate to appear after 36 months of storage, and the solid content, i.e., the content of active ingredients, decreased.

[0111] The reason for the decreased stability of the medicinal wine is inferred to be:

[0112] Comparative Example 1 did not undergo oxygenation during the post-treatment standing process, resulting in a relatively lower solid content in the prepared medicinal wine compared to Examples 1-3 of this invention, meaning that the dissolution of the effective components was lower. In addition, no corresponding centrifugation and freezing treatments were performed during the post-treatment process, and a large number of macromolecules and poorly soluble components in the medicinal wine will settle and precipitate during long-term storage (18 months), meaning that the stability of the medicinal wine is not high.

[0113] Comparative Example 2 did not undergo freezing treatment during the post-processing, causing some poorly soluble components in the medicinal wine to settle and precipitate during long-term storage (36 months), indicating that the medicinal wine was not very stable.

[0114] Comparative Examples 3 and 4 used only one centrifugation operation, which was not very effective in removing macromolecules and poorly soluble substances. As a result, some poorly soluble components in the medicinal wine precipitated and separated during long-term storage (24 months), indicating that the medicinal wine was not very stable.

[0115] Although Comparative Example 5 used two centrifugation processes, the operating parameters were not within the scope of protection of this invention. Although it could remove macromolecules and insoluble substances to a certain extent, the effect was not good. As a result, some insoluble components in the medicinal wine precipitated and precipitated during long-term storage (36 months), that is, the stability of the medicinal wine was not high.

[0116] During the storage of medicated wine, the precipitation and sedimentation of solids will lead to a decrease in the content of active ingredients in the medicated wine, thus affecting the efficacy of the medicated wine and customer satisfaction.

[0117] In summary, only the medicated wine prepared by the method provided in the present invention has better stability and no precipitation will occur after long-term storage.

[0118] II. Pharmacodynamic experiment

[0119] 1. Experimental purpose

[0120] To evaluate the analgesic and anti-inflammatory effects of the medicated wine.

[0121] 2 Experimental materials

[0122] 2.1 Experimental animals

[0123] Kunming mice (SPF grade), weighing 20±2 g, provided by the Guangdong Provincial Center for Medical Laboratory Animals. Animal quality certificate: SCXK (Guangdong) 2019-0002. The animals were housed in a SPF-class barrier environment at a temperature of 20-25°C and a relative humidity of 40-70%. After normal feeding for 3 days, they were used for the test. Experimental animal use license: SYXK (Guangdong) 2017-0125.

[0124] 2.2 Drugs and reagents

[0125] The medicated wine prepared in Example 3: Specification 500 mL / bottle (containing 7.3 g of crude drug).

[0126] Preparation of the drug: Take an appropriate amount of the medicated wine prepared in Example 3, rotary evaporate it at 45°C until there is no alcohol smell, place it in a freeze dryer and freeze-dry it to prepare 85 mg of crude drug / g of freeze-dried powder for standby. When in use, it is reconfigured with distilled water to the required concentration for the test.

[0127] Dosage reference:

[0128] The medicated wine prepared in Example 3: Adults are orally administered 2 times a day, 15 mL each time. Calculated based on an adult weight of 60 kg, the average dosage is 7.3 mg of crude drug / kg / d. The equivalent dosage for mice is calculated as: 7.3 mg / kg / d × 12 times = 87.6 mg of crude drug / kg / d; in this experiment, the low, medium, and high dosages designed for mice are 90, 180, and 360 mg of crude drug / kg / d respectively.

[0129] Aspirin tablets: Bayer Healthcare Co., Ltd., batch number: BJ41406; The daily clinical dose for adults is 50-300 mg. Since 300-600 mg of aspirin can be used clinically to relieve fever and pain, a dose of 300 mg / day is adopted. Based on an adult weight of 60 kg, the dosage is 5 mg / kg / day. The equivalent dose for mice is: 5 mg / kg / day × 12 times = 60 mg / kg / day.

[0130] Glacial acetic acid: Tianjin Fuyu Fine Chemical Co., Ltd., batch number: 20200810.

[0131] 2.3 Experimental Apparatus

[0132] Cold and heat pain sensor (Beijing Youcheng Jiaye Co., Ltd., 35100); rotary evaporator (Shanghai Ailang Instrument Co., Ltd., N-1200A); freeze dryer (Beijing Boyikang Experimental Instrument Co., Ltd., Lab-1A-80E); Infinite 200PRO multi-functional microplate reader (Tecan Austria gmbH).

[0133] 3. Methods and Results

[0134] 3.1 Effect on heat-induced pain in mice (hot plate test)

[0135] Female KM mice, weighing 18-22g, were randomly divided into a blank control group, an aspirin positive control group, and low, medium, and high dose groups of the medicated wine, with 15 mice in each group. Mice in each group were administered the drug via gavage for 5 consecutive days, once daily, at a volume of 20mL / kg. The blank control group received an equal volume of physiological saline. At 30 and 60 minutes after the last administration, the pain threshold of each group was measured, and the percentage increase in pain threshold was calculated. The differences between groups were compared, and the results are shown in Table 2.

[0136]

[0137] Table 2. Effects of medicinal wine on heat-induced pain in mice (n=15, mean ± standard deviation)

[0138]

[0139] Note: Compared with the blank control group, *P<0.05, **P<0.01

[0140] Compared with the blank control group, after 30 minutes of administration, the percentage increase in pain threshold in mice in the aspirin positive control group was significantly prolonged (P < 0.05), and the percentage increase in pain threshold in the medium dose group of Example 3 was significantly prolonged (P < 0.01); after 60 minutes of administration, the percentage increase in pain threshold in both the aspirin positive control group and the medium dose group of Example 3 was significantly prolonged (P < 0.01); indicating that the prepared medicinal wine has a significant inhibitory effect on pain caused by heat stimulation.

[0141] 3.2 Effects on acetic acid-induced pain in mice (writhing test)

[0142] KM mice, half male and half female, weighing 18-22g, were randomly divided into a blank control group, an aspirin positive control group, and low, medium, and high dose groups of the medicated wine, with 15 mice in each group. Each group was administered the corresponding drug via gavage, while the blank control group received an equal volume of physiological saline. Administration was once daily at a volume of 20mL / kg for 5 consecutive days. One hour after the last administration, 0.2mL of 0.6% acetic acid saline solution was injected intraperitoneally per mouse. The number of writhing movements in the mice within 15 minutes was observed and recorded, and differences between groups were compared. The results are shown in Table 3.

[0143] Table 3 Effect of medicinal wine on analgesic effect in mice (n=15, mean ± standard deviation)

[0144]

[0145] Note: Compared with the blank control group, *P<0.05, ** P < 0.01

[0146] Compared with the blank control group, the number of writhing movements in mice in each treatment group decreased significantly (P<0.01), indicating that the prepared medicinal wine has a significant inhibitory effect on pain caused by chemical substances.

[0147] 3.3 Effects on acetic acid-induced peritoneal capillary permeability in mice

[0148] KM mice, half male and half female, weighing 18-22g, were randomly divided into a blank control group, an aspirin positive control group, and low, medium, and high dose groups of medicated wine, with 15 mice in each group. Each group was administered the corresponding drug by gavage, while the blank control group was given an equal volume of physiological saline. Administration was once daily at a volume of 20ml / kg for 8 consecutive days. One hour after the last administration, each group of mice was injected intravenously with 0.1ml / 10g of body weight of 0.5% Evans blue physiological saline solution, followed immediately by an intraperitoneal injection of 0.2mL / mouse of 0.6% acetic acid. Twenty minutes later, the mice were euthanized by cervical dislocation. The abdominal cavity was opened, rinsed several times with 5mL of physiological saline, and the wash solution was collected and diluted to 10mL. The solution was centrifuged at 1000rpm for 5min, and 500μL of the supernatant was measured at 620nm. Differences among the groups were compared, and the results are shown in Table 4.

[0149] Table 4. Effects of medicinal wine on acetic acid-induced peritoneal capillary permeability in mice (n=15, mean ± standard deviation)

[0150]

[0151] Note: Compared with the blank control group, *P<0.05, ** P < 0.01

[0152] Compared with the blank control group, the high-dose group of Example 3 could significantly inhibit the increase in peritoneal capillary permeability in mice induced by acetic acid (P<0.01); the aspirin positive control group, the low- and medium-dose groups of Example 3 could inhibit the increase in peritoneal capillary permeability in mice induced by acetic acid (P<0.05), indicating that the medicinal wine prepared in Example 3 has the effect of inhibiting inflammatory exudation.

[0153] The above embodiments are only used to illustrate the technical solutions of the present invention and not to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art can still make modifications or equivalent substitutions to the specific implementation schemes of the present invention, and these modifications or equivalent substitutions do not depart from the spirit and scope of the present invention, and are all within the protection scope of the claims of the present invention.

Claims

1. The application of a medicinal wine in the preparation of analgesic and anti-inflammatory drugs, characterized in that: The preparation method of the medicinal wine includes the following steps: (1) Crushing: First, mix and grind 60 parts of Amomum villosum, 120 parts of cinnamon, 60 parts of white cardamom, 30 parts of red cardamom, 60 parts of Piper longum, and 30 parts of agarwood. Then add 15 parts of processed Polygonum multiflorum, 15 parts of Rehmannia glutinosa, 15 parts of Angelica dahurica, 15 parts of Dioscorea opposita, 15 parts of Galla chinensis, 15 parts of Pogostemon cablin, 30 parts of ginseng, 15 parts of Morus alba root bark, 15 parts of Erythrina variegata bark, 15 parts of Nardostachys jatamansi, 15 parts of Angelica pubescens, 15 parts of Atractylodes lancea, 15 parts of Ligusticum chuanxiong, 15 parts of Cuscuta chinensis, 15 parts of Poria cocos, 15 parts of Citrus reticulata peel, 15 parts of Amomum tsao-ko, 15 parts of Cornus officinalis, 15 parts of Aconitum carmichaelii, 30 parts of Magnolia officinalis, 15 parts of Citrus reticulata peel, 15 parts of Schisandra chinensis, 15 parts of Achyranthes bidentata, 30 parts of Citrus aurantium, 30 parts of Alpinia galanga, and 15 parts of Kaempferia galanga. Coltsfoot flower 15 parts, fennel 240 parts, platycodon root 60 parts, prepared rehmannia root 30 parts, acorus root 30 parts, atractylodes rhizome 45 parts, areca nut 45 parts, licorice root 30 parts, angelica root 90 parts, gentian root 15 parts, safflower 60 parts, turmeric root 15 parts, lotus seed 15 parts, papaya 15 parts, ophiopogon root 15 parts, notopterygium root 15 parts, cyperus rhizome 15 parts, cistanche deserticola 15 parts, astragalus root 15 parts, asparagus root 15 parts, peach kernel 15 parts, gardenia fruit 15 parts, alisma rhizome 15 parts, lindera root 15 parts, pinellia tuber 15 parts, arisaema rhizome 15 parts, bitter almond 15 parts, poria cocos 30 parts, polygala root 15 parts, epimedium root 15 parts, sparganium rhizome 15 parts, and rubia root 15 parts are mixed and pulverized to obtain a mixture. (2) Extraction: Mix 158,000 parts of baijiu (Chinese liquor), 900 parts of red yeast rice, and other ingredients, heat to a boil, then cool to obtain a mixed liquid. (3) Settling and separation: Take the medicine solution, seal it and let it stand. During the standing process, compressed air needs to be introduced and stirred. After the standing is completed, separate the supernatant and the suspension to obtain the medicine solution. The step of separating the supernatant involves using a horizontal scraper centrifuge with an 80-mesh sieve, a discharge rate of 4-6 r / min, a feed rate of 8-12 r / min, and a centrifugation rate of 40-44 r / min. The step of separating the suspension involves using a horizontal screw discharge sedimentation turbine centrifuge with a drum speed of 2400-3000 r / min and a differential speed of 23-28 r / min. (4) Freezing and filtration: The medicinal liquid is frozen and stored, and then filtered to obtain the medicinal wine. The freezing temperature is ≤-3℃, and the storage time is 7-10 days.

2. The application according to claim 1, characterized in that: The particle size of the mixture in step (1) is 24-50 mesh.

3. The application according to claim 1, characterized in that: The heating in step (2) is steam heating, with a heating temperature of 75-85℃; the cooling temperature in step (2) is 25-30℃.

4. The application according to claim 1, characterized in that: The pressure of the compressed air in step (3) is ≥0.40MPa; the settling time is more than 2 months. During the first 15 days of the settling process, compressed air needs to be introduced every day and the mixture needs to be stirred for 10-20 minutes.

5. The application according to claim 1, characterized in that: The filtration described in step (4) is carried out using a diatomaceous earth filter, with a pressure ≥0.1MPa after the soil is applied and a final filtration pressure ≤0.35MPa.

6. The application according to claim 1, characterized in that: The drug has at least one of the following effects: (1) It can suppress pain caused by heat stimulation; (2) It can suppress pain caused by chemical substances.

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