Meridian dredging pill and preparation method thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicine preparations, and discloses a collateral dredging pill which comprises collateral dredging extract fine powder, an enteric coating layer and a gastric-soluble film coating layer. The invention also discloses a preparation method of the pill, which comprises the following steps of: preparing the vein and collateral dredging extract into small pills or granules, coating the enteric coating, further preparing the pills, and coating the stomach-soluble film coating to obtain the pill. Compared with traditional collateral dredging granules and pills, the collateral dredging enteric-coated pill preparation can effectively improve the drying speed of the pill, is regular in appearance, good in fluidity and small in weight difference, can reduce the bad smell of the preparation under the condition that a flavoring agent is not used, improves the medication compliance of a patient, can be accurately positioned to disintegrate, release and absorb, and has a good application prospect. Meanwhile, the stability of the medicine is improved. As an upgraded and updated new product of traditional collateral dredging granules and pills, the traditional Chinese medicine composition has a wide market development prospect.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine preparation technology, specifically relating to a blood vessel smoothing pill and its preparation method. Background Art

[0002] The Meridian Unblocking Prescription originates from the clinically proven formula of Master Tang Zuxuan, a renowned traditional Chinese medicine practitioner. It is derived from ancestral formulas, combined with other formulas such as Dang Gui Bu Xue Tang, Shao Yao Gan Cao Tang, Si Miao Yong An Tang, and Zhi Jing San. It inherits the advantages of these formulas while compensating for their shortcomings, achieving a synergistic and comprehensive effect. The formula uses Astragalus membranaceus and Lonicera japonica as the principal herbs, which invigorate qi and promote diuresis, clear heat and detoxify, purge yin fire, detoxify muscles, clear foulness, and treat accumulated toxins. Phellodendron amurense, Atractylodes lancea, Coix lacryma-jobi, Angelica sinensis, Paeonia lactiflora, and Scrophularia ningpoensis are the assistant herbs, which clear heat and remove dampness, nourish blood, relieve spasms, harmonize the blood and relieve pain, soften hardness and dissipate nodules, reduce swelling and detoxify, and unblock the meridians. Leech, scorpion, and centipede are the adjuvant herbs, which invigorate blood and remove blood stasis, attack toxins and dissipate nodules, unblock the meridians and relieve pain. Licorice is the guiding herb to harmonize the other herbs. The combination of these herbs works synergistically to clear heat and detoxify, resolve blood stasis and unblock the meridians, and promote diuresis and reduce swelling. It is mainly used for thrombophlebitis caused by damp-heat obstructing the meridians, and for lower limb swelling, pain, dark red skin, or cord-like structures caused by non-acute deep vein thrombosis. The medicine is specific and potent, and has achieved good clinical efficacy.

[0003] Mailuoshutong Granules obtained a new drug certificate (Class 3 new traditional Chinese medicine) and production license in 1998. Mailuoshutong Granules (sugar-free) obtained a supplementary drug application license in 2012, and Mailuoshutong Pills (concentrated pills) obtained a drug registration license in 2009. All of these are exclusively produced domestically and possess independent intellectual property rights regarding their prescriptions, processes, and uses. The launch of this product filled a market gap in domestic and international traditional Chinese medicine treatments for damp-heat stagnation in the meridians, and it was the first approved traditional Chinese medicine for the targeted treatment of thrombophlebitis. Currently, this product remains the only approved drug in the domestic pharmaceutical market for the symptomatic treatment of thrombophlebitis, suitable for long-term treatment of thrombophlebitis. Clinical application has demonstrated its definite efficacy, earning high praise from both doctors and patients, and playing a significant role in the treatment of clinical venous thrombosis and thrombophlebitis.

[0004] The current method for preparing the Meridian Soothing Pill involves pulverizing half the amount of leeches, centipedes, and scorpions into a fine powder; soaking honeysuckle, atractylodes, scrophularia, angelica, and white peony in water for 3 hours, then distilling for 7 hours to extract the volatile oil, collecting the volatile oil, and adding an appropriate amount of β-cyclodextrin to prepare an inclusion complex. The distilled residue, along with the remaining leeches, centipedes, scorpions, and the remaining four herbs (including astragalus), are decocted twice with water, each time for 1.5 hours. The decoctions and the aqueous solution after volatile oil extraction are combined, filtered, and the filtrate is concentrated to a clear extract with a relative density of 1.10–1.20 (80℃). Ethanol is added to achieve an alcohol content of 60%, and the mixture is allowed to stand for 24 hours. It is then filtered, the ethanol is recovered under reduced pressure, and the extract is concentrated to a clear extract with a relative density of 1.10–1.18 (80℃), spray-dried into a fine powder, and mixed with the above-mentioned fine powder of leeches, the volatile oil inclusion complex, and an appropriate amount of starch. The mixture is then made into pills and dried to obtain the final product.

[0005] Although the Mailuoshutong series of products have good clinical efficacy, they have shortcomings such as poor taste and easy moisture absorption. The reason is that the formula contains three raw materials: leech, centipede and scorpion. These materials contain a large amount of protein, fat and alkaloids. These components, after oxidation and decomposition, will produce an unpleasant and foul odor, especially a fishy smell.

[0006] CN110123968A discloses a method for preparing a pulmonase-relieving preparation. This method employs a dual extraction process involving alcohol reflux and water decoction, allowing for the comprehensive and thorough extraction of both fat-soluble and water-soluble active ingredients. This avoids resource waste, improves the effectiveness of the preparation, and avoids directly using finely powdered animal materials, reducing the strong fishy odor and alleviating nausea and vomiting during administration, thus improving patient compliance. While this method effectively reduces the fishy odor of animal materials, prolonged heating can lead to protein denaturation, thereby reducing the content of active ingredients in the preparation.

[0007] CN116098970A discloses a method for preparing a vascular endothelial extract. This method involves microfiltration and ultrafiltration of three animal-derived medicinal materials—leeches, scorpions, and centipedes—followed by freeze-drying. This effectively removes the fishy odor of the animal-derived medicinal materials, reduces the amount of dried extract powder, and, while ensuring the extraction of all components from the animal-derived medicinal materials, reduces the dosage and improves the taste. While this method effectively improves the taste of the preparation, it is relatively cumbersome and has a long production cycle.

[0008] While the above methods improve the taste of the preparation to some extent, the disintegration of Mailuoshutong Pills in the stomach after ingestion releases a strong, fishy odor. This odor stimulates the phrenic nerve, causing spasms in the diaphragm. The fishy smell, accompanied by belching, rises to the oral and nasal mucosa, making it unacceptable to patients. Some patients experience nausea and vomiting, severely impacting the clinical use of Mailuoshutong preparations and patient adherence. Traditional pill-making methods are particularly challenging due to the unique properties of Mailuoshutong Pills, including a large amount of extract and fine animal powder. The preparation process is extremely rigorous; even slight mishandling can cause surface hardening of the pills, preventing internal moisture evaporation and leading to excessive moisture content and substandard quality. Therefore, a new preparation method for Mailuoshutong Pills is urgently needed to improve patient experience and the stability of the preparation. Summary of the Invention

[0009] The purpose of this invention is to provide a Mailuoshutong intestinal pill and its preparation method, especially a Mailuoshutong enteric-coated pill and its preparation method, to solve the problems of discomfort caused by the taste of existing Mailuoshutong series products and easy moisture absorption during the storage of the preparation.

[0010] The technical solution of the present invention is as follows: a Mailuoshutong pill, comprising Mailuoshutong extract fine powder, an enteric coating layer, and a gastric coating layer.

[0011] A type of blood vessel-relieving pill, by weight percentage, contains the following ingredients:

[0012] A. Fine powder of Meridian Relaxant Extract 60%-80%;

[0013] B. Enteric coating 10%-35%;

[0014] C. Gastric coating: 5%-10%.

[0015] Preferably, a blood vessel smoothing pill contains the following ingredients by weight percentage:

[0016] A. Fine powder of Meridian Relaxant Extract 60%-65%;

[0017] B. Enteric coating 20%-30%;

[0018] C. Gastric coating: 8%-10%.

[0019] Preferably, the enteric coating material is selected from one or more of shellac, acrylic resins (I, II, III), cellulose acetate phthalate (CAP), and hydroxypropyl methylcellulose phthalate (HPMCP).

[0020] Preferably, the enteric coating material is selected from acrylic resins; more preferably, the enteric coating material is selected from acrylic resin No. II and / or No. III.

[0021] In a preferred embodiment, the enteric coating material is a mixture of acrylic resins II and III in a mass ratio of 4 to 5:1.

[0022] This invention does not limit the materials used for gastric-coating films; any gastric-coating film disclosed in the prior art can be used to achieve this invention. Commonly used gastric-coating film layer materials include hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), acrylic resin No. IV, polyvinylpyrrolidone (PVP), or polyvinyl acetal diethylamine acetic acid (AEA), etc.

[0023] This invention does not limit the preparation method of the fine powder of the Meridian Soothing Extract; those skilled in the art can prepare it using existing methods.

[0024] A method for preparing a pulverizing pill includes: finely powdering a pulverizing extract, adding ethanol to make a soft material, making granules or small pills, coating with an enteric coating, drying, adding a gliding agent to compress the pills, and coating with a gastric-soluble film to obtain the final product.

[0025] The pellets are prepared by either pan-forming or plasticizing; plasticizing is preferred, and extrusion spheronization is even more preferred.

[0026] Preferably, the enteric coating is applied by spraying. The spraying method can be aerosol spraying, where the VeinSoothing Pills or Granules are placed on an air distribution plate. An airflow entering through the air distribution plate carries the VeinSoothing Pills or Granules upwards, spraying the enteric coating solution. Bottom air intake and top spraying or bottom perforated plate spraying of the enteric solution can be used for coating.

[0027] It should be noted that the bottom air intake can be implemented using the existing method, with the air distribution plate allowing the pulse-relieving pills or granules to rise in a straight line.

[0028] Preferably, the air distribution plate has multiple air inlets, and the multiple air inlets are designed to make the incoming airflow rise in a spiral shape, with the arterial meridian-relieving pills or particles spiraling upward.

[0029] Preferably, the flow aid is magnesium stearate or silicon dioxide.

[0030] In one embodiment, the fine powder of the vascular vasodilator extract is first made into enteric-coated pellets, and then further made into pills.

[0031] A method for preparing the above-mentioned Meridian-Soothing Pills includes the following steps:

[0032] (1) Weigh out the prescribed amount of fine powder of the Meridian Soothing Extract, add the wetting agent ethanol solution and knead to form a soft material, which is then extruded into strips by an extruder.

[0033] (2) Place the strips obtained in step (1) into a rolling mill to make small pills, dry them, and sieve them to obtain small pills for relieving blood stasis.

[0034] (3) Prepare enteric coating solution, place the pulse relief pills on the air distribution plate, heat the compressed air machine, and the pills rise in a spiral shape with the airflow. The peristaltic pump sprays compressed air to transport the enteric coating solution to the top spray and atomize it onto the surface of the pills.

[0035] (4) After the small pellets are evenly coated with enteric coating liquid, turn off the peristaltic pump and the top spray compressed air, and continue drying until the enteric coating is completely dry to obtain the enteric coated pellets of the Meridian Relaxing Pills;

[0036] (5) After mixing the enteric-coated granules obtained in step (4) with the glidin, compress them into pellets;

[0037] (6) Coat the obtained Meridian Soothing Pills in step (5) with a gastric dissolving film using a high-efficiency coating pan.

[0038] In step (1), the fine powder of the Meridian Soothing Extract is weighed according to the prescription amount, and ethanol solution is added as a wetting agent to knead and form a soft material. The soft material is then extruded into strips of the same diameter that are smooth and dense.

[0039] Preferably, the concentration of the wetting agent ethanol solution is 80%-95%.

[0040] Preferably, the volume of the added wetting agent ethanol solution is 10%-20% of the mass of the fine powder of the Meridian Soothing Extract, wherein the volume is in mL and the mass is in g.

[0041] Preferably, the extruder orifice diameter is 0.8mm-1.6mm.

[0042] Preferably, in step (2), the rolling mill is turned on, and the strip obtained in step (1) is placed in the high-speed rotating rolling mill to make small pellet semi-finished products. The small pellet semi-finished products are then taken out and dried at 50-60℃, and sieved to obtain small pellets of 20-30 mesh.

[0043] Preferably, the intestinal coating solution in step (3) is a mixture of acrylic resin No. II and No. III, with a mass ratio of 4 to 5:1.

[0044] Preferably, the enteric coating solution is prepared by dissolving acrylic resins II and III in an appropriate amount of 80-90% ethanol solution, adding an appropriate amount of emulsifier and plasticizer, and stirring to dissolve.

[0045] In another embodiment, the fine powder of the vascular vasodilator extract is first made into enteric-coated granules and then further made into pills.

[0046] A method for preparing the above-mentioned Meridian-Soothing Pills includes the following steps:

[0047] (1) Weigh out the prescribed amount of fine powder of the Meridian Soothing Extract, add the wetting agent ethanol solution and knead to make a soft material;

[0048] (2) Place the soft material obtained in step (1) into a gyratory pellet mill to make pellets, dry them, and sieve them to obtain the vein-clearing pellets.

[0049] (3) Prepare enteric coating solution, place the granules on the air distribution plate, compress air and heat, the granules rise in a spiral shape with the airflow, turn on the peristaltic pump to spray compressed air, transport the enteric coating solution to the top spray and atomize it onto the surface of the granules.

[0050] (4) After the enteric coating solution has been evenly coated, turn off the peristaltic pump and the top spray compressed air, and continue drying. After the granular enteric coating layer is completely dry, the Vein Relief Enteric Coated Granules are obtained.

[0051] (5) Mix the enteric-coated granules of Pulsostomy and the glidin agent, and then compress them into pellets;

[0052] (6) Using a high-efficiency coating pan, coat the blood-dissolving pills from step (5) with a gastric-dissolving film to obtain the product.

[0053] Preferably, the concentration of the wetting agent ethanol solution is 80%-95%.

[0054] Preferably, the volume of the added wetting agent ethanol solution is 10%-20% of the mass of the pulmonale extract, wherein the volume is in mL and the mass is in g.

[0055] Preferably, the enteric coating material in step (3) is selected from acrylic resin or Opadry; preferably, the enteric coating material is selected from acrylic resin II and / or acrylic resin III; more preferably, the enteric coating material is a mixture of acrylic resin II and acrylic resin III, with a mass ratio of 4-5:1.

[0056] While *Pulse-Clearing Pills* are primarily absorbed in the small intestine, their disintegration in the stomach produces a strong, fishy odor, which can lead to vomiting in severe cases, affecting patient compliance and reducing efficacy. This invention employs a two-layer coating process: first, the small pills or granules of *Pulse-Clearing Pills* are intestinal-coated, and then the pills, after adding a glidant, are coated with a gastric-dissolving film. The *Pulse-Clearing Pills* prepared by this invention undergo two disintegration processes upon entering the body. First, they disintegrate into small pills or granules in the stomach, eliminating the fishy odor and improving patient compliance. Second, they undergo a secondary disintegration in the small intestine, ensuring the absorption of all active ingredients and maximizing efficacy.

[0057] The beneficial effects of using this method to prepare Pulse-Clearing Enteric-Coated Pills are as follows:

[0058] (1) First, prepare the extract of the vascular vasodilator into small pills or granules. The small pills or granules have a large specific surface area, which makes it easier for the moisture inside the preparation to evaporate, shorten the drying time, simplify the operation, and reduce the failure rate of the preparation.

[0059] (2) The enteric-coated pills of the present invention have a regular shape, are spherical or near-spherical, have a smooth and round surface, and have good fluidity.

[0060] (3) The enteric-coated pills of the present invention can disintegrate and be absorbed in intestinal fluid, which fundamentally solves the discomfort caused by disintegration in the stomach and meets the needs of better absorption of drugs in the intestines and treatment; it can effectively improve the drying speed of pills and improve the problems of moisture absorption and instability of the preparation of the drug. Detailed Implementation

[0061] To make the objectives, technical solutions, and advantages of the embodiments of this application clearer, the technical solutions in the embodiments of this application will be clearly and completely described below. Reagents or instruments whose manufacturers are not specified can all be commercially available conventional products.

[0062] The fine powder of the extract from the Meridian Soothing Pill described in the following examples was prepared using the following method:

[0063]

[0064] (1) Take 1 / 2 of the prescription amount of leeches, centipedes and scorpions, and grind them into ultrafine powder;

[0065] (2) Soak honeysuckle, atractylodes lancea, scrophularia, angelica sinensis and white peony in water for 1-4 hours, distill for 6-8 hours, collect the volatile oil for later use, and use the residue and aqueous solution after distillation for later use.

[0066] (3) Take the volatile oil from step (2) and refine it with β-cyclodextrin to prepare an inclusion complex;

[0067] (4) Take the dregs from step (2) and the remaining amount of leeches, centipedes, scorpions, as well as the amount of astragalus, phellodendron, coix seed and licorice in the prescription, add water and decoct to obtain the decoction;

[0068] (5) Combine the aqueous solution of step (2) and the decoction of step (4), filter, concentrate to obtain clear paste, add ethanol, let stand, filter, recover ethanol under reduced pressure and concentrate to obtain thick paste, dry with belt vacuum, and pulverize into fine powder.

[0069] (6) Mix the ultrafine powder obtained in step (1), the volatile oil inclusion complex obtained in step (3), and the fine powder obtained in step (5) to obtain the fine powder of the Meridian Soothing Extract, and set aside for later use.

[0070] Example 1: Preparation of Pulse-Clearing Enteric-Coated Pills

[0071] (1) Weigh 650g of the fine powder of the Meridian Soothing Extract according to the prescription, add 100mL of 85% ethanol solution and knead to form a soft material. Extrude strips into strips using an extruder with a hole diameter of 1.0mm.

[0072] (2) Place the strips obtained in step (1) into a rolling mill to make small pills, dry at 55°C for 15 hours, and sieve through a 20-mesh sieve to obtain 561g of Meridian Relaxing Pills.

[0073] (3) Weigh 200g of acrylic resin II and 50g of acrylic resin III, add an appropriate amount of 85% ethanol, stir evenly, and store in a sealed container for 24 hours. After complete dissolution, add an appropriate amount of diethyl phthalate, castor oil, and Tween 80, then add 85% ethanol and stir evenly. Filter to obtain enteric coating solution for later use. Place the pulse-relieving pills on the air distribution plate, heat them with a compressed air machine, and the pills rise in a spiral shape with the airflow. The peristaltic pump sprays compressed air from the top to deliver the enteric coating solution to the top spray and atomize it onto the surface of the pills.

[0074] (4) After the small pills are evenly coated with enteric coating liquid, turn off the peristaltic pump and the top spray compressed air, and continue to dry for 6 hours until the enteric coating is completely dry, to obtain 785g of Pulse-relieving enteric-coated small pills;

[0075] (5) After mixing the enteric-coated granules obtained in step (4) with an appropriate amount of starch and 0.5% magnesium stearate, press them into pellets.

[0076] (6) Coat the Mailuoshutong pills obtained in step (5) with a gastric coating film using a high-efficiency coating pan to increase the weight by 8%, thereby obtaining 1000g of Mailuoshutong enteric-coated pills.

[0077] Example 2: Preparation of Pulse-Clearing Enteric-Coated Pills

[0078] (1) Weigh 650g of the fine powder of the Meridian Soothing Extract according to the prescription, add 100mL of 85% ethanol solution and knead to form a soft material. Extrude strips into strips using an extruder with a hole diameter of 1.0mm.

[0079] (2) Place the strips obtained in step (1) into a rolling mill to make small pills, dry at 50°C for 17 hours, and sieve through a 20-mesh sieve to obtain 545g of Meridian Relaxing Pills.

[0080] (3) Weigh 150g of acrylic resin II and 100g of acrylic resin III, add an appropriate amount of 80% ethanol, stir evenly, and store in a sealed container for 24 hours. After complete dissolution, add an appropriate amount of diethyl phthalate, castor oil, and Tween 80, then add 80% ethanol and stir evenly. Filter to obtain enteric coating solution for later use. Place the pulse-relieving pills on the air distribution plate, heat them with a compressed air machine, and the pills rise in a spiral shape with the airflow. The peristaltic pump sprays compressed air from the top to deliver the enteric coating solution to the top sprayer and atomize it onto the surface of the pills.

[0081] (4) After the small pills are evenly coated with enteric coating solution, turn off the peristaltic pump and the top spray compressed air, and continue drying for 8.5 hours until the enteric coating is completely dry, to obtain 739g of enteric-coated small pills for the Meridian Soothing Treatment.

[0082] (5) After mixing the enteric-coated granules obtained in step (4) with an appropriate amount of starch and 1.0% silica, press them into pellets.

[0083] (6) Coat the Mailuoshutong pills obtained in step (5) with a gastric coating film using a high-efficiency coating pan to increase the weight by 8%, thereby obtaining 1000g of Mailuoshutong enteric-coated pills.

[0084] Example 3: Preparation of Pulse-Clearing Enteric-Coated Pills

[0085] (1) Weigh 800g of the fine powder of the Meridian Soothing Extract according to the prescription, add 80mL of 80% ethanol solution and knead to form a soft material. Extrude strips into strips using an extruder with a bore diameter of 1.6mm.

[0086] (2) Place the strips obtained in step (1) into a rolling mill to make small pills, dry at 60°C for 16 hours, and sieve through a 20-mesh sieve to obtain 698g of blood vessel smoothing pills.

[0087] (3) Weigh 150g of acrylic resin I and add an appropriate amount of water to make an aqueous dispersion; take an appropriate amount of distilled water, add an appropriate amount of glyceryl monostearate, Tween 80 and triethyl citrate, heat to 70°C, homogenize with a homogenizer to obtain a suspension, add the acrylic resin I aqueous dispersion, stir evenly and set aside; place the pulse relief pills on the air distribution plate, heat with a compressed air machine, the pills rise in a spiral shape with the airflow, and the peristaltic pump sprays compressed air to deliver the enteric coating solution to the top spray and atomize it onto the surface of the pills.

[0088] (4) After the small pills are evenly coated with enteric coating liquid, turn off the peristaltic pump and the top spray compressed air, and continue to dry for 7 hours until the enteric coating is completely dry, to obtain 813g of enteric-coated small pills for the Meridian Soothing Pills;

[0089] (5) After mixing the enteric-coated granules obtained in step (4) with an appropriate amount of starch and 0.3% magnesium stearate, compress them into granules.

[0090] (6) Coat the Mailuoshutong pills obtained in step (5) with a gastric coating film using a high-efficiency coating pan to increase the weight by 5%, thereby obtaining 1000g of Mailuoshutong enteric-coated pills.

[0091] Example 4: Preparation of Pulse-Clearing Enteric-Coated Pills

[0092] (1) Weigh 600g of the fine powder of the Meridian Soothing Extract according to the prescription, add 120mL of 80% ethanol solution and knead to form a soft material. Extrude strips into strips using an extruder with a bore diameter of 0.8mm.

[0093] (2) Place the strips obtained in step (1) into a rolling mill to make small pills, dry at 55°C for 12 hours, and sieve through a 30-mesh sieve to obtain 533g of Meridian Relaxing Pills.

[0094] (3) Weigh 100g of hydroxypropyl methylcellulose phthalate, add an appropriate amount of acetone-ethanol mixed solution with a volume ratio of 1:1, add an appropriate amount of talc powder and diethyl phthalate, stir to dissolve, filter and set aside; place the pulse relief pills on the air distribution plate, heat with the compressed air machine, the pills rise in a spiral shape with the airflow, the peristaltic pump sprays compressed air from the top, and delivers the enteric coating solution to the top spray and atomizes it onto the surface of the pills;

[0095] (4) After the small pills are evenly coated with enteric coating liquid, turn off the peristaltic pump and the top spray compressed air, and continue to dry for 9 hours until the enteric coating is completely dry, to obtain 586g of enteric-coated small pills for the Meridian Soothing Pills;

[0096] (5) After mixing the enteric-coated granules obtained in step (4) with an appropriate amount of starch and 0.3% magnesium stearate, compress them into granules.

[0097] (6) Coat the Mailuoshutong pills obtained in step (5) with a gastric coating film using a high-efficiency coating pan to increase the weight by 10%, thereby obtaining 1000g of Mailuoshutong enteric-coated pills.

[0098] Example 5: Preparation of Pulse-Clearing Enteric-Coated Pills

[0099] (1) Weigh 650g of fine powder of the Meridian Soothing Extract, add 100mL of 80% ethanol solution and knead to make a soft material;

[0100] (2) Place the soft material obtained in step (1) into a gyratory pellet mill, make it into pellets, dry it for 10 hours, sieve it, and obtain 552g of Meridian Relaxing Granules.

[0101] (3) Weigh 280g of acrylic resin II and 70g of acrylic resin III, add an appropriate amount of 85% ethanol, stir evenly, and store in a sealed container for 24 hours. After complete dissolution, add an appropriate amount of diethyl phthalate, castor oil, and Tween 80, then add 85% ethanol and stir evenly. Filter to obtain enteric coating solution for later use. Place the granules on the air distribution plate, compress air and heat them. The granules rise in a spiral shape with the airflow. Turn on the peristaltic pump and spray compressed air to deliver the enteric coating solution to the top spray and atomize it onto the surface of the granules.

[0102] (4) After the enteric coating solution has been evenly coated, turn off the peristaltic pump and the top spray compressed air, and continue to dry for 4 hours. After the granular enteric coating layer is completely dry, 728g of Mailuoshutong enteric granules are obtained.

[0103] (5) Mix the enteric-coated granules of Pulse-Soothing Granules with an appropriate amount of starch and 0.5% magnesium stearate, and then compress them into pellets;

[0104] (6) Using a high-efficiency coating pan, coat the enteric-coated pills from step (5) with a gastric coating film to increase their weight by 6%, thus obtaining 1000g of enteric-coated pills.

[0105] Example 6: Preparation of Pulse-Clearing Enteric-Coated Pills

[0106] (1) Weigh 700g of fine powder of the Meridian Soothing Extract, add 140mL of 90% ethanol solution and knead to make a soft material;

[0107] (2) Place the soft material obtained in step (1) into a gyratory pellet mill, make it into pellets, dry it for 12 hours, sieve it, and obtain 637g of Meridian Relaxing Granules.

[0108] (3) Weigh 280g of cellulose acetate phthalate, add an appropriate amount of a mixed solution of ethanol and acetone with a volume ratio of 1:1 and stir to dissolve, then add an appropriate amount of diethyl phthalate, stir to dissolve and filter for later use; place the granules on the air distribution plate, compress air and heat, the granules rise in a spiral shape with the airflow, turn on the peristaltic pump to spray compressed air, and deliver the enteric coating solution to the top spray and atomize it onto the surface of the granules;

[0109] (4) After the enteric coating solution is evenly coated, turn off the peristaltic pump and the top spray compressed air, and continue to dry for 6 hours. After the granular enteric coating layer is completely dry, 771g of Mailuoshutong enteric granules are obtained.

[0110] (5) Mix the enteric-coated granules of Pulse-Soothing Granules with an appropriate amount of starch and 0.3% magnesium stearate, and then compress them into pellets;

[0111] (6) Using a high-efficiency coating pan, coat the Mailuoshutong pills from step (5) with a gastric-coated film to increase their weight by 8%, thus obtaining 1000g of Mailuoshutong enteric-coated pills.

[0112] Example 7: Preparation of Pulse-Clearing Enteric-Coated Pills

[0113] (1) Weigh 650g of fine powder of the Meridian Soothing Extract, add 100mL of 95% ethanol solution and knead to make a soft material;

[0114] (2) Place the soft material obtained in step (1) into a gyratory pellet mill, make it into pellets, dry it for 5 hours, sieve it, and obtain 579g of Meridian Relaxing Granules.

[0115] (3) Weigh 250g of acrylic resin II, add an appropriate amount of ethanol and stir to dissolve, then add an appropriate amount of triethyl citrate, talc powder, and methyl silicone oil, stir to dissolve, filter and set aside; place the granules on the air distribution plate, compress air and heat, the granules rise in a spiral shape with the airflow, turn on the peristaltic pump to spray compressed air, transport the enteric coating liquid to the top spray and atomize it onto the surface of the granules.

[0116] (4) After the enteric coating solution has been evenly coated, turn off the peristaltic pump and the top spray compressed air, and continue to dry for 4 hours. After the granular enteric coating layer is completely dry, 665g of Mailuoshutong enteric granules are obtained.

[0117] (5) Mix the enteric-coated granules of Pulse-Soothing Granules with an appropriate amount of starch and 0.3% magnesium stearate, and then compress them into pellets;

[0118] (6) Using a high-efficiency coating pan, coat the Mailuoshutong pills from step (5) with a gastric-coated film to increase their weight by 8%, thus obtaining 1000g of Mailuoshutong enteric-coated pills.

[0119] Example 8: Preparation of Pulse-Clearing Enteric-Coated Pills

[0120] (1) Weigh 650g of the fine powder of the Meridian Soothing Extract according to the prescription, add 100mL of 85% ethanol solution and knead to form a soft material. Extrude strips into strips using an extruder with a hole diameter of 1.0mm.

[0121] (2) Place the strips obtained in step (1) into a rolling mill to make small pills, dry at 55°C for 15 hours, and sieve through a 20-mesh sieve to obtain 547g of blood vessel smoothing pills.

[0122] (3) Weigh 250g of acrylic resin III, add an appropriate amount of 85% ethanol, stir evenly, and store in a sealed container for 24 hours. After it is completely dissolved, add an appropriate amount of diethyl phthalate, castor oil, and Tween 80, then add 85% ethanol and stir evenly. Filter to obtain enteric coating solution for later use. Place the pulse relief pills on the air distribution plate, heat them with a compressed air machine, and the pills rise in a spiral shape with the airflow. The peristaltic pump sprays compressed air from the top to deliver the enteric coating solution to the top spray and atomize it onto the surface of the pills.

[0123] (4) After the small pills are evenly coated with enteric coating liquid, turn off the peristaltic pump and the top spray compressed air, and continue to dry for 6 hours until the enteric coating is completely dry, to obtain 737g of enteric-coated small pills for the Meridian Soothing Pills;

[0124] (5) After mixing the enteric-coated granules obtained in step (4) with an appropriate amount of starch and 0.5% magnesium stearate, press them into pellets.

[0125] (6) Coat the Mailuoshutong pills obtained in step (5) with a gastric coating film using a high-efficiency coating pan to increase the weight by 8%, thereby obtaining 1000g of Mailuoshutong enteric-coated pills.

[0126] Comparative Example 1: Preparation of Pulse-Clearing Enteric-Coated Pills

[0127] (1) Weigh 650g of fine powder of the Meridian Soothing Extract, add 100mL of 85% ethanol solution and knead to make a soft material;

[0128] (2) Place the soft material obtained in step (1) into a gyratory pellet mill, make it into pellets, dry it for 5 hours, sieve it, and obtain 587g of Meridian Relaxing Granules.

[0129] (3) Mix the granules with an appropriate amount of starch and 0.3% magnesium stearate, and then compress them into pellets;

[0130] (4) Using a high-efficiency coating pan, coat the enteric-coated pills from step (5) with a gastric coating film to increase their weight by 8%, thus obtaining 1000g of enteric-coated pills.

[0131] Comparative Example 2: Preparation of Pulse-Clearing Enteric-Coated Pills

[0132] Weigh 650g of fine powder of the extract of the Meridian Soothing Pill, add an appropriate amount of starch and mix well, add an appropriate amount of 85% ethanol solution to make a soft material, make pills, and dry in a forced-air drying oven for 36 hours to obtain 1000g of Meridian Soothing Pills.

[0133] Experiment Example 1: Release Rate Experiment

[0134] The enteric-coated pills prepared in Examples 1, 2, 5, 7, and 8 of this invention, and the pills prepared in Comparative Examples 1 and 2, were subjected to in vitro release tests in media at pH 1.2 and pH 6.8, under conditions of water bath temperature of 37℃±0.5℃ and rotation speed of 100r / min, according to the dissolution and release determination method (General Chapter 0931, Part IV, Chinese Pharmacopoeia 2020). Astragaloside A was used as an indicator for the evaluation.

[0135] Medium preparation:

[0136] pH 1.2 medium: Take 2.0g of sodium chloride, add an appropriate amount of water to dissolve it, then add 7mL of hydrochloric acid, and dilute with water to 1000mL.

[0137] pH 6.8 medium: Take 1.7g of potassium dihydrogen phosphate and 1.775g of anhydrous disodium hydrogen phosphate, add an appropriate amount of water to dissolve, and dilute with water to 1000mL.

[0138] Chromatographic conditions: octadecylsilane-bonded silica gel was used as the stationary phase; acetonitrile:water = 32:68 was used as the mobile phase; evaporative light scattering detector was used for detection. The theoretical plate number, calculated based on the astragaloside A peak, should be no less than 4000.

[0139] Preparation of the reference solution: Accurately weigh an appropriate amount of astragaloside A reference standard, add methanol to prepare a solution containing 0.2 mg / mL. Preparation of the test solution: Take 5 mL of the sample at each time point, and simultaneously add 5 mL of distilled water at the same temperature. Filter the sample through a 0.45 μm microporous membrane. Take 2 mL of the filtrate and extract four times with 15 mL of water-saturated n-butanol each time. Combine the n-butanol extracts and wash twice with concentrated ammonia solution, 20 mL each time. Let stand for 30 minutes, discard the washings, recover the solvent from the n-butanol solution to dryness, dissolve the residue in methanol, transfer to a 2 mL volumetric flask, add methanol to the mark, shake well, filter, and take the filtrate. Assay: Inject 20 μL of the standard solution and sample solution respectively. Calculate the content of astragaloside A in the sample using the external standard two-point method logarithmic equation, and calculate the cumulative release percentage of astragaloside A at each time point. The results are shown in Table 1-2.

[0140] Table 1 Release rates of each sample in dissolution medium at pH 1.2

[0141]

[0142] Table 2 Release rates of each sample in dissolution medium at pH 6.8

[0143]

[0144]

[0145] As can be seen from the data in Table 1-2, the enteric-coated pills prepared by the present invention are basically not released in simulated gastric fluid, and the cumulative release rate is no more than 15% in 90 minutes; while the pills prepared in the comparative example are able to be released in simulated gastric fluid, with a release rate of more than 95% in 90 minutes; and are able to be basically completely released in simulated intestinal fluid, with a release rate of more than 90% in 90 minutes.

Claims

1. A Mailuoshutong pill, comprising Mailuoshutong extract fine powder, an enteric coating layer, and a gastric film coating layer.

2. The pill according to claim 1, characterized in that By mass percentage, the fine powder of Mailuoshutong extract is 60%-80%, the enteric coating layer is 10%-35%, and the gastric soluble film coating layer is 5%-10%.

3. The pill according to claim 2, characterized in that Calculated by mass percentage, the fine powder of Mailuoshutong extract is 60%-65%, the enteric coating layer is 20%-30%, and the gastric soluble film coating layer is 8%-10%.

4. The pill according to any one of claims 1 to 3, characterized in that The enteric coating material is selected from one or more of shellac, acrylic resin No. Ⅰ, acrylic resin No. Ⅱ, acrylic resin No. Ⅲ, cellulose acetate phthalate CAP, and hydroxypropyl methylcellulose phthalate HPMCP.

5. The pill according to claim 4, characterized in that The enteric coating material is a mixture of acrylic resin No. II and acrylic resin No. III.

6. The method for preparing the Mailuo Shutong pills according to any one of claims 1 to 5, characterized in that: The method comprises the following steps: adding a wetting agent to fine powder of the Mailuoshutong extract to prepare a soft material, preparing granules or pellets, coating the pellets with an enteric coating, adding a flow aid to press the pellets after drying, and coating the pellets with a gastric soluble film coating.

7. The preparation method according to claim 6, characterized in that: The wetting agent is an ethanol solution with a concentration of 80%-95%.

8. The preparation method according to claim 7, characterized in that: The added volume of the wetting agent ethanol solution is 10%-20% of the mass of the Mailuoshutong extract fine powder, wherein the volume is measured in mL and the mass is measured in g.

9. The preparation method according to claim 6, characterized in that: First, the fine powder of Mailuoshutong extract is made into enteric-coated pellets, and then further made into pills; the steps include: (1) weighing a prescribed amount of Mailuoshutong extract powder, adding ethanol solution and kneading to form a soft material, and extruding it through an extruder to obtain a strip; (2) placing the strip obtained in step (1) into a spheronizer to form small pellets, drying, and sieving to obtain Mailuo Shutong small pellets; (3) preparing the enteric coating solution, placing the Mailuoshutong pills on an air distribution plate, heating them with a compressed air machine, causing the pills to rise in a spiral shape along with the air flow, and using a peristaltic pump to spray compressed air from the top to deliver the enteric coating solution to the top spray and atomize it onto the surface of the pills; (4) After the pellets are evenly coated with the enteric coating solution, the peristaltic pump and the top spray compressed air are turned off, and drying is continued until the enteric coating is completely dry to obtain Mailuo Shutong enteric-coated pellets; (5) mixing the Mailuoshutong enteric-coated pellets obtained in step (4) and the glidant, and pressing the pellets; (6) coating the Mailuo Shutong pills obtained in step (5) with a gastric soluble film coating using a high-efficiency coating pan to obtain the product.

10. The preparation method according to claim 6, characterized in that: Firstly, the fine powder of Mailuoshutong extract is made into enteric-coated granules, and then further made into pills; the steps include: (1) Weighing a prescribed amount of Mailuoshutong extract powder, adding ethanol solution and kneading to form a soft material; (2) placing the soft material obtained in step (1) into a swing granulator to make granules, drying, and sieving to obtain the Mailuo Shutong granules; (3) Prepare enteric coating liquid, place Mailuo Shutong granules on an air distribution plate, compress air and heat, so that the granules rise in a spiral shape along with the air flow, turn on the peristaltic pump to spray compressed air from the top, transport the enteric coating liquid to the top spray and atomize it onto the surface of the granules; (4) After the enteric coating liquid is evenly coated, the peristaltic pump and the top spray compressed air are turned off, and the drying is continued. After the enteric coating layer of the granules is completely dried, the Mailuo Shutong enteric granules are obtained; (5) mixing the Mailuoshutong enteric-coated granules and the glidant and pressing the mixture into pellets; (6) Using a high-efficiency coating pan, coat the Mailuo Shutong pills prepared in step (5) with a gastric-soluble film coating to obtain the resultant.

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