A pharmaceutical composition of wuwei mosha pills and a preparation method and use thereof

Abstract

The present application relates to a kind of medicine composition of five-flavor musk pill and its preparation method and purposes, and the medicine composition is made of fructus chebulae (nucleus), black grass wu, radix aucklandiae, bupleurum smithii, artificial musk.The content of aconitine is controlled at 0.3-0.5% by using supercritical extraction, back extraction and other extraction methods to treat black grass wu in the present application, the content of toxic substance is reduced, and the poisoning reaction of five-flavor musk pill long-term use is avoided.

Description

Technical Field

[0001] This invention belongs to the field of Tibetan medicine technology, and specifically relates to a pharmaceutical composition of Five-Flavor Musk Pill, its preparation method and uses. Background Technology

[0002] Five-Flavor Musk Pill is a Tibetan medicine variety included in the Chinese Pharmacopoeia. This medicine is composed of musk, chebula, black aconite, costus root, and Tibetan calamus. It has anti-inflammatory, analgesic, and wind-dispelling effects and is used for tonsillitis, pharyngitis, influenza, anthrax, rheumatoid arthritis, neuralgia, stomachache, toothache, and other diseases.

[0003] Black aconite, a Tibetan medicine known as "Iron Stick Hammer," primarily contains aconitine alkaloids. Modern chemical and pharmacological studies have shown that aconitine alkaloids are both the active and toxic components of black aconite, including diester, monoester, amino alcohol, and other types. Diester alkaloids are both important active ingredients and highly toxic; monoester alkaloids have lower efficacy and toxicity than diester alkaloids. Oral administration of 0.2 mg of pure aconitine can cause poisoning symptoms; oral administration of 3-5 mg of pure aconitine can be fatal.

[0004] Domestic literature reports that due to historical reasons, there are significant differences in the raw materials, processing methods, and formulation techniques of the same type of Tibetan medicine produced by different regions and manufacturers. The Chinese Pharmacopoeia includes aconite in its prescription for Wuwei Shexiang Wan (Five-Flavor Musk Pill), specifying that the aconite is pulverized, mixed with other drugs, and then made into pills with benzoin-saturated water. This demonstrates the considerable differences in the use of the drug and the preparation process of Wuwei Shexiang Wan among different regions and manufacturers. Clinical reports indicate that the symptoms of poisoning from Wuwei Shexiang Wan are essentially similar to those of aconitine poisoning; therefore, the presence of aconite in the prescription is one of the important factors contributing to the varying toxicity of this drug.

[0005] Domestic literature reports extraction methods for total aconitine alkaloids in Aconitum carmichaelii, including methods such as soaking, boiling, steaming, ultrasonic extraction, percolation, reflux extraction, and resin adsorption. Content determination methods were studied, and the effective content was confirmed. Domestic literature also reports that processing techniques can reduce the toxicity of Aconitum carmichaelii, but there is a lack of quality control standards for processing this toxic drug, and no relevant data proves that its toxicity is reduced.

[0006] In recent years, there have been domestic clinical reports of poisoning caused by taking Wuwei Shexiang Pills. In conclusion, because Wuwei Shexiang Pills contain aconite root, long-term use can lead to poisoning. Summary of the Invention

[0007] This invention aims to solve the technical problems existing in the prior art. To this end, this invention proposes a five-flavor musk pill pharmaceutical composition, its preparation method, and its uses. By employing extraction methods such as extraction and back-extraction, the content of toxic substances in aconite root is reduced, thus avoiding poisoning reactions that may occur with long-term use of five-flavor musk pills.

[0008] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0009] The first aspect of this invention relates to a pharmaceutical composition made from the following parts by weight of active pharmaceutical ingredient:

[0010] Terminalia chebula (pitted) 38.9%, Aconitum carmichaelii 39.2%, Aucklandia lappa 12.9%, Acorus calamus 7.7%, Musk 1.3%,

[0011] The aconitine content in the black aconite is 0.3-0.5%.

[0012] The musk is preferably synthetic musk.

[0013] The present invention also provides a method for preparing the above-mentioned pharmaceutical composition, comprising the following steps:

[0014] (1) Grinding and sieving

[0015] The Terminalia chebula (without the pit), Aconitum carmichaelii, Aucklandia lappa, Acorus calamus, and artificial musk were first screened to remove visible foreign matter, and then crushed and sieved.

[0016] (2) Extraction

[0017] A saturated sodium bicarbonate solution was prepared using purified water.

[0018] Black aconite root is mixed with a saturated sodium bicarbonate solution and stored in a sealed container at room temperature.

[0019] After preservation, transfer it to the extraction vessel for supercritical extraction;

[0020] After supercritical extraction, extract A and solid B were obtained.

[0021] Solid B was subjected to reduced pressure, washed with water, and then dried.

[0022] (3) Back-extraction

[0023] Prepare a hydrochloric acid solution with a pH of 3-4 using purified water;

[0024] Hydrochloric acid solution was added to extract A for back-extraction, followed by liquid-liquid separation. The organic phase was collected, concentrated under reduced pressure, washed with water, and dried to obtain solid C.

[0025] (4) Mixing and sieving

[0026] The seeds of Terminalia chebula (without the pit), solid B, solid C, costus root, and calamus were mixed and sieved to obtain mixture D.

[0027] (5) Total Mixing

[0028] Artificial musk and mixture D were divided into 5 portions and mixed in equal increments. After mixing, the mixture was sieved to obtain the raw powder of Five-Flavor Musk Pills.

[0029] (6) Mixing, pelleting and drying

[0030] Prepare a saturated aqueous solution of benzoin using purified water;

[0031] Five-flavor musk pill raw powder and benzoin saturated aqueous solution were respectively fed into a fully automatic pill-making machine to obtain five-flavor musk pills.

[0032] The crushing and sieving mentioned in step (1) refers to: using a crusher to crush each raw material and passing it through a 200m mesh sieve.

[0033] In step (2),

[0034] The amount of saturated sodium bicarbonate used is:

[0035] Wblack aconite : Vsaturated sodium bicarbonate solution = 1 kg : 0.1-0.2 L;

[0036] The stirring time is 40-60 minutes, and the sealed storage time is 120-160 minutes;

[0037] The supercritical extraction process involves adding moistened black aconite to the extraction vessel, starting the supercritical extraction device, setting the pressure to 15 MPa and the temperature to 45°C, and stabilizing the CO2 flow rate at 20-30 kg / h. Then, isopropyl acetate is injected as an entrainer from the entrainer pump. After stabilizing the extraction for 120-160 minutes, the device valves are closed sequentially to stop the extraction. The entrainer dosage is: W black aconite : L entrainer = 1 kg : 1.5-2 L.

[0038] The pressure reduction refers to raising the temperature of solid B to 80-85℃, controlling the pressure at -0.1-0MPa, and maintaining the pressure for 20-30 minutes.

[0039] The water washing process involves adding purified water to solid B, stirring for 20-40 minutes, filtering, and then drying until the moisture content is less than 5%. The amount of purified water used is 3-5 times that of solid B.

[0040] In step (3),

[0041] The amount of hydrochloric acid solution used is:

[0042] Vextract A : Vhydrochloric acid solution = 1L : 2-4L;

[0043] The back extraction refers to mixing extract A with hydrochloric acid solution, heating the mixture to 40-45℃, stirring for 40-60 minutes, then letting it stand for 20-40 minutes to separate the liquid and collect the organic phase.

[0044] The aforementioned vacuum concentration refers to pressure controlled at -0.1 to 0 MPa and temperature controlled at 82 to 86°C.

[0045] The washing and drying process refers to adding purified water to the solid obtained by vacuum concentration, stirring for 20-40 minutes, filtering, and then drying until the moisture content is less than 5%. The amount of purified water used is 3-5 times that of the solid.

[0046] In step (5), sieving refers to passing through a 200m mesh sieve.

[0047] The present invention also provides the use of the above-described pharmaceutical composition or the pharmaceutical composition prepared by the above-described preparation method in the preparation of anti-inflammatory, analgesic, and wind-dispelling drugs.

[0048] The technical advantages of this invention are:

[0049] 1. Technological advantages

[0050] Domestic literature reports extraction methods for total aconitine alkaloids from Aconitum carmichaelii, including methods such as soaking, boiling, steaming, ultrasonic extraction, percolation, reflux extraction, and resin adsorption. Content determination methods were studied, and the effective content was confirmed. However, the following problems exist:

[0051] (1) Boiling, steaming and other processes can easily cause the raw materials to be heated and charred, and the resulting products decompose at high temperatures, which reduces their application value.

[0052] (2) The extraction, percolation and other processes use a large amount of organic solvents, and the extraction yield is low and the cycle is long.

[0053] (3) Extraction processes such as ultrasonic and macroporous resin adsorption tend to result in higher extraction costs, higher equipment maintenance costs, and longer production cycles.

[0054] This invention employs supercritical CO2 extraction technology. CO2 is a safe, non-toxic, and inexpensive liquid that can rapidly penetrate solid substances to extract their essence. It features high efficiency, resistance to oxidation, natural composition, and no chemical pollution. The extraction process is easy to control, produces products with no solvent residue, offers high safety, and combines extraction and separation into one process. It is currently widely used in plant extraction both domestically and internationally.

[0055] 2. It can effectively reduce the content of aconitine alkaloids in black aconite.

[0056] Experiments have shown that the content of aconitine alkaloids in Aconitum carmichaelii is generally 1.2-1.5%. After processing according to the Chinese Pharmacopoeia, the content of aconitine alkaloids in Aconitum carmichaelii is generally 0.7-1%. Using the process of this invention, the content of aconitine alkaloids in Aconitum carmichaelii is generally 0.3-0.5%.

[0057] 3. Avoid poisoning reactions

[0058] The method described in this invention for producing Five-Flavor Musk Pills can effectively reduce toxicity. During the course of treatment, it can effectively prevent poisoning reactions. Specific implementation methods

[0059] The invention is illustrated below with examples. It should be understood that these examples are for illustrative purposes only and not for limiting the invention. The scope and core content of the invention are defined by the claims.

[0060] Example 1

[0061] Terminalia chebula (pitted) 38.9kg, Aconitum carmichaelii 39.2kg, Aucklandia lappa 12.9kg, Acorus calamus 7.7kg, Artificial musk 1.3kg;

[0062] Tests showed that the content of aconitine alkaloids in black aconite was 1.38%, or 0.54 kg.

[0063] (1) Grinding and sieving

[0064] The seeds of Terminalia chebula (without the pit), Aconitum carmichaelii, Aucklandia lappa, Acorus calamus, and artificial musk were first screened to remove visible foreign matter, and then crushed and passed through a 200-mesh sieve.

[0065] (2) Extraction

[0066] A saturated sodium bicarbonate solution was prepared using purified water.

[0067] 39.2 kg of black aconite was stirred and mixed with 4 L of saturated sodium bicarbonate solution for 40 min, and then stored in a sealed container at room temperature for 120 min.

[0068] After preservation, the sample was transferred to an extraction vessel for supercritical extraction: Moistened aconite root was added to the extraction vessel, and the supercritical extraction apparatus was started. The pressure and temperature of the extraction vessel were set to 15 MPa and 45°C, respectively. After the CO2 flow rate stabilized at approximately 20 kg / h, 58.8 L of isopropyl acetate was injected as an entrainer from the entrainer pump. After stabilizing the extraction for 120 min, the valves were closed sequentially to stop the extraction. Solid-liquid separation yielded 58.7 L of extract A and solid B, respectively.

[0069] Solid B was heated to 80℃, and the pressure was controlled at -0.1 to 0 MPa for 20 minutes; 38.76 kg of solid B was obtained.

[0070] Add 116.3 L of purified water to solid B, stir for 20 min, filter, and dry until the moisture content reaches 4.5%.

[0071] (3) Back-extraction

[0072] Prepare a hydrochloric acid solution with a pH of 3 using purified water;

[0073] 118 L of hydrochloric acid solution was added to extract A for back-extraction, followed by liquid-liquid separation. The organic phase was collected, concentrated under reduced pressure, washed with water, and dried to obtain solid C.

[0074] Tests showed that the total weight of solids B and C was 38.6 kg, and the content of aconitine alkaloids was 0.47%.

[0075] (4) Mixing and sieving

[0076] The seeds of Terminalia chebula (without the pit), solid B, solid C, costus root, and calamus were mixed and sieved to obtain mixture D.

[0077] (5) Total Mixing

[0078] Artificial musk and mixture D were divided into 5 portions and mixed in equal increments. After mixing, the mixture was sieved to obtain the raw powder of Five-Flavor Musk Pills.

[0079] (6) Mixing, pelleting and drying

[0080] Prepare a saturated aqueous solution of benzoin using purified water;

[0081] Five-flavor musk pill raw powder and benzoin saturated aqueous solution were respectively fed into a fully automatic pill-making machine to obtain five-flavor musk pills.

[0082] Testing showed that the product quality meets the quality standards of the current edition of the Chinese Pharmacopoeia for "Five-Flavor Musk Pills".

[0083] Example 2

[0084] Terminalia chebula (pitted) 38.9kg, Aconitum carmichaelii 39.2kg, Aucklandia lappa 12.9kg, Acorus calamus 7.7kg, Artificial musk 1.3kg;

[0085] Tests showed that the content of aconitine alkaloids in black aconite was 1.41%, or 0.55 kg.

[0086] (1) Grinding and sieving

[0087] The seeds of Terminalia chebula (without the pit), Aconitum carmichaelii, Aucklandia lappa, Acorus calamus, and artificial musk were first screened to remove visible foreign matter, and then crushed and passed through a 200-mesh sieve.

[0088] (2) Extraction

[0089] A saturated sodium bicarbonate solution was prepared using purified water.

[0090] 39.2 kg of black aconite was stirred and mixed with 4.7 L of saturated sodium bicarbonate solution for 45 min, and then stored in a sealed container at room temperature for 130 min.

[0091] After preservation, the sample was transferred to an extraction vessel for supercritical extraction: moistened aconite root was added to the extraction vessel, and the supercritical extraction device was started. The pressure and temperature of the extraction vessel were set to 15 MPa and 45°C, respectively. After the CO2 flow rate stabilized at approximately 22 kg / h, 63 L of isopropyl acetate was injected as an entrainer from the entrainer pump. After stabilizing the extraction for 130 min, the valves of the device were closed sequentially to stop the extraction. Solid-liquid separation yielded 62.9 L of extract A and solid B, respectively.

[0092] Solid B was heated to 81℃, and the pressure was controlled at -0.1 to 0 MPa for 20 minutes; 38.63 kg of solid B was obtained.

[0093] Add 135 L of purified water to solid B, stir for 25 min, filter and dry until the moisture content reaches 4.3%.

[0094] (3) Back-extraction

[0095] Prepare a hydrochloric acid solution with a pH of 3.3 using purified water;

[0096] 157 L of hydrochloric acid solution was added to extract A for back-extraction, followed by liquid-liquid separation. The organic phase was collected, concentrated under reduced pressure, washed with water, and dried to obtain solid C.

[0097] Tests showed that the total weight of solids B and C was 38.1 kg, and the content of aconitine alkaloids was 0.43%.

[0098] (4) Mixing and sieving

[0099] The seeds of Terminalia chebula (without the pit), solid B, solid C, costus root, and calamus were mixed and sieved to obtain mixture D.

[0100] (5) Total Mixing

[0101] Artificial musk and mixture D were divided into 5 portions and mixed in equal increments. After mixing, the mixture was sieved to obtain the raw powder of Five-Flavor Musk Pills.

[0102] (6) Mixing, pelleting and drying

[0103] Prepare a saturated aqueous solution of benzoin using purified water;

[0104] Five-flavor musk pill raw powder and benzoin saturated aqueous solution were respectively fed into a fully automatic pill-making machine to obtain five-flavor musk pills.

[0105] Testing showed that the product quality meets the quality standards of the current edition of the Chinese Pharmacopoeia for "Five-Flavor Musk Pills".

[0106] Example 3

[0107] Terminalia chebula (pitted) 38.9kg, Aconitum carmichaelii 39.2kg, Aucklandia lappa 12.9kg, Acorus calamus 7.7kg, Artificial musk 1.3kg;

[0108] Tests showed that the content of aconitine alkaloids in black aconite was 1.37%, or 0.54 kg.

[0109] (1) Grinding and sieving

[0110] The seeds of Terminalia chebula (without the pit), Aconitum carmichaelii, Aucklandia lappa, Acorus calamus, and artificial musk were first screened to remove visible foreign matter, and then crushed and passed through a 200-mesh sieve.

[0111] (2) Extraction

[0112] A saturated sodium bicarbonate solution was prepared using purified water.

[0113] 39.2 kg of black aconite was stirred and mixed with 5.9 L of saturated sodium bicarbonate solution for 50 min, and then stored in a sealed container at room temperature for 140 min.

[0114] After preservation, the sample was transferred to an extraction vessel for supercritical extraction: moistened aconite root was added to the extraction vessel, and the supercritical extraction device was started. The pressure and temperature of the extraction vessel were set to 15 MPa and 45°C, respectively. After the CO2 flow rate stabilized at approximately 25 kg / h, 67 L of isopropyl acetate was injected as an entrainer from the entrainer pump. After stabilizing the extraction for 140 min, the valves of the device were closed sequentially to stop the extraction. Solid-liquid separation yielded 66.9 L of extract A and solid B, respectively.

[0115] Solid B was heated to 83℃, and the pressure was controlled at -0.1 to 0 MPa for 25 minutes; 38.59 kg of solid B was obtained.

[0116] Add 154 L of purified water to solid B, stir for 30 min, filter and dry until the moisture content reaches 4.1%.

[0117] (3) Back-extraction

[0118] Prepare a hydrochloric acid solution with a pH of 3.5 using purified water;

[0119] 200 L of hydrochloric acid solution was added to extract A for back-extraction, followed by liquid-liquid separation. The organic phase was collected, concentrated under reduced pressure, washed with water, and dried to obtain solid C.

[0120] Tests showed that the total weight of solids B and C was 38.4 kg, and the content of aconitine alkaloids was 0.31%.

[0121] (4) Mixing and sieving

[0122] The seeds of Terminalia chebula (without the pit), solid B, solid C, costus root, and calamus were mixed and sieved to obtain mixture D.

[0123] (5) Total Mixing

[0124] Artificial musk and mixture D were divided into 5 portions and mixed in equal increments. After mixing, the mixture was sieved to obtain the raw powder of Five-Flavor Musk Pills.

[0125] (6) Mixing, pelleting and drying

[0126] Prepare a saturated aqueous solution of benzoin using purified water;

[0127] Five-flavor musk pill raw powder and benzoin saturated aqueous solution were respectively fed into a fully automatic pill-making machine to obtain five-flavor musk pills.

[0128] Testing showed that the product quality meets the quality standards of the current edition of the Chinese Pharmacopoeia for "Five-Flavor Musk Pills".

[0129] Example 4

[0130] Terminalia chebula (pitted) 38.9kg, Aconitum carmichaelii 39.2kg, Aucklandia lappa 12.9kg, Acorus calamus 7.7kg, Artificial musk 1.3kg;

[0131] Tests showed that the content of aconitine alkaloids in black aconite was 1.23%, or 0.48 kg.

[0132] (1) Grinding and sieving

[0133] The seeds of Terminalia chebula (without the pit), Aconitum carmichaelii, Aucklandia lappa, Acorus calamus, and artificial musk were first screened to remove visible foreign matter, and then crushed and passed through a 200-mesh sieve.

[0134] (2) Extraction

[0135] A saturated sodium bicarbonate solution was prepared using purified water.

[0136] 39.2 kg of black aconite was stirred and mixed with 6.6 L of saturated sodium bicarbonate solution for 55 min, and then stored in a sealed container at room temperature for 150 min.

[0137] After preservation, the sample was transferred to an extraction vessel for supercritical extraction: Moistened aconite root was added to the extraction vessel, and the supercritical extraction apparatus was started. The pressure and temperature of the extraction vessel were set to 15 MPa and 45°C, respectively. After the CO2 flow rate stabilized at approximately 27 kg / h, 70 L of isopropyl acetate was injected as an entrainer from the entrainer pump. After stabilizing extraction for 150 min, the valves were closed sequentially to stop the extraction. Solid-liquid separation yielded 69.9 L of extract A and solid B, respectively.

[0138] Solid B was heated to 84℃, and the pressure was controlled at -0.1 to 0 MPa for 27 minutes; 38.68 kg of solid B was obtained.

[0139] Add 174 L of purified water to solid B, stir for 35 min, filter and dry until the moisture content reaches 3.9%.

[0140] (3) Back-extraction

[0141] Prepare a hydrochloric acid solution with a pH of 3.7 using purified water;

[0142] 245 L of hydrochloric acid solution was added to extract A for back-extraction, followed by liquid-liquid separation. The organic phase was collected, concentrated under reduced pressure, washed with water, and dried to obtain solid C.

[0143] Tests showed that the total weight of solids B and C was 38.6 kg, and the content of aconitine alkaloids was 0.36%.

[0144] (4) Mixing and sieving

[0145] The seeds of Terminalia chebula (without the pit), solid B, solid C, costus root, and calamus were mixed and sieved to obtain mixture D.

[0146] (5) Total Mixing

[0147] Artificial musk and mixture D were divided into 5 portions and mixed in equal increments. After mixing, the mixture was sieved to obtain the raw powder of Five-Flavor Musk Pills.

[0148] (6) Mixing, pelleting and drying

[0149] Prepare a saturated aqueous solution of benzoin using purified water;

[0150] Five-flavor musk pill raw powder and benzoin saturated aqueous solution were respectively fed into a fully automatic pill-making machine to obtain five-flavor musk pills.

[0151] Testing showed that the product quality meets the quality standards of the current edition of the Chinese Pharmacopoeia for "Five-Flavor Musk Pills".

[0152] Example 5

[0153] Terminalia chebula (pitted) 38.9kg, Aconitum carmichaelii 39.2kg, Aucklandia lappa 12.9kg, Acorus calamus 7.7kg, Artificial musk 1.3kg;

[0154] Tests showed that the content of aconitine alkaloids in black aconite was 1.36%, or 0.53 kg.

[0155] (1) Grinding and sieving

[0156] The seeds of Terminalia chebula (without the pit), Aconitum carmichaelii, Aucklandia lappa, Acorus calamus, and artificial musk were first screened to remove visible foreign matter, and then crushed and passed through a 200-mesh sieve.

[0157] (2) Extraction

[0158] A saturated sodium bicarbonate solution was prepared using purified water.

[0159] 39.2 kg of black aconite was stirred and mixed with 7.8 L of saturated sodium bicarbonate solution for 60 min, and then stored in a sealed container at room temperature for 160 min.

[0160] After preservation, the sample was transferred to an extraction vessel for supercritical extraction: Moistened aconite root was added to the extraction vessel, and the supercritical extraction apparatus was started. The pressure and temperature of the extraction vessel were set to 15 MPa and 45°C, respectively. After the CO2 flow rate stabilized at approximately 30 kg / h, 78 L of isopropyl acetate was injected as an entrainer from the entrainer pump. After stabilizing extraction for 160 min, the valves were closed sequentially to stop the extraction. Solid-liquid separation yielded 77.9 L of extract A and solid B, respectively.

[0161] Solid B was heated to 85°C, and the pressure was controlled at -0.1 to 0 MPa for 30 minutes; 38.55 kg of solid B was obtained.

[0162] Add 192 L of purified water to solid B, stir for 40 min, filter and dry until the moisture content reaches 4.0%.

[0163] (3) Back-extraction

[0164] Prepare a hydrochloric acid solution with a pH of 4.0 using purified water;

[0165] 311 L of hydrochloric acid solution was added to extract A for back-extraction, followed by liquid-liquid separation. The organic phase was collected, concentrated under reduced pressure, washed with water, and dried to obtain solid C.

[0166] Tests showed that the total weight of solids B and C was 38.59 kg, and the content of aconitine alkaloids was 0.42%.

[0167] (4) Mixing and sieving

[0168] The seeds of Terminalia chebula (without the pit), solid B, solid C, costus root, and calamus were mixed and sieved to obtain mixture D.

[0169] (5) Total Mixing

[0170] Artificial musk and mixture D were divided into 5 portions and mixed in equal increments. After mixing, the mixture was sieved to obtain the raw powder of Five-Flavor Musk Pills.

[0171] (6) Mixing, pelleting and drying

[0172] Prepare a saturated aqueous solution of benzoin using purified water;

[0173] Five-flavor musk pill raw powder and benzoin saturated aqueous solution were respectively fed into a fully automatic pill-making machine to obtain five-flavor musk pills.

[0174] Testing showed that the product quality meets the quality standards of the current edition of the Chinese Pharmacopoeia for "Five-Flavor Musk Pills".

[0175] Example 6

[0176] Pharmacological experiment content: Effect of acetic acid on the writhing response in mice.

[0177] 1. Materials

[0178] 1.1 Medications:

[0179] Model group: No medication administered.

[0180] Control group: Wuwei Musk Pills (Ningxia Duowei Pharmaceutical Co., Ltd.)

[0181] Experimental group: Five-flavor Musk Pills (prepared using the process described in Example 1 of this invention).

[0182] 1.2 Animals

[0183] Rats: weighing 210–240 g.

[0184] Quantity: 40.

[0185] 2. Methods and Results

[0186] 2.1 Method

[0187] Forty rats were randomly divided into four groups based on body weight and sex. The following administrations were administered to each group: control group 0.030 g / kg; experimental group 0.030 g / kg; normal group administered an equal volume of distilled water by gavage; model group received no administration. Each group received one dose. One hour after administration, each rat was intraperitoneally injected with 0.2 ml of 0.5% acetic acid. After a 5-minute acclimatization period, the number of writhing responses observed in each group within 10 minutes was observed, and a t-test was performed.

[0188] 2.2 Results

[0189] See the table below for details.

[0190] Effects of Wuwei Musk Pills on Writhing Response in Mice

[0191] Group Number <![CDATA[Dose administered / (g·kg -1 )]]> Number of twists / times normal group 10 0 11.5±3.2 Model group 10 0 24.0±5.7* control group 10 0.03 11.2±4.7** experimental group 10 0.03 12.1±4.2**

[0192] Note: Compared with the control group, * indicates P < 0.01, ** indicates P < 0.05.

[0193] The Ridit test showed that the lesions in the model group were significantly different from those in the normal group (P<0.01); compared with the model group, the lesions in both the control group and the experimental group were significantly reduced (P<0.05).

[0194] The results showed that both the control group and the experimental group significantly inhibited the acetic acid-induced writhing response in mice, and the differences were statistically significant compared with the blank control group (P < 0.01).

[0195] The results showed that the dosage of the control group was consistent with that of the product described in this invention, and the analgesic and protective effects were comparable. This indicates that the Five-Flavor Musk Pill prepared in this invention has the same efficacy as the traditional Five-Flavor Musk Pill.

Claims

1. A pharmaceutical composition comprising the following parts by weight of active pharmaceutical ingredient: The pharmaceutical composition comprises 38.9% deseeded Terminalia chebula, 39.2% Aconitum carmichaelii, 12.9% Aucklandia lappa, 7.7% Acorus tatarinowii, and 1.3% artificial musk. The preparation method of the pharmaceutical composition includes the following steps: (1) Grinding and sieving The pitted Terminalia chebula, Aconitum carmichaelii, Aucklandia lappa, Acorus calamus, and artificial musk were first screened to remove visible foreign matter, and then crushed and sieved. (2) Extraction A saturated sodium bicarbonate solution was prepared using purified water. Black aconite root is mixed with a saturated sodium bicarbonate solution and stored in a sealed container at room temperature. After preservation, transfer it to the extraction vessel for supercritical extraction; After supercritical extraction, extract A and solid B were obtained. Solid B was subjected to depressurization, washing with water, and then de-core drying, wherein: The amount of saturated sodium bicarbonate used is: Wblack aconite : Vsaturated sodium bicarbonate solution = 1 kg : 0.1-0.2 L; The stirring time is 40-60 minutes, and the sealed storage time is 120-160 minutes; The supercritical extraction refers to the following steps: moistened black aconite is added to the extraction vessel, the supercritical extraction device is started, the pressure of the extraction vessel is set to 15 MPa, the temperature of the extraction vessel is set to 45℃, and after the CO2 flow rate is basically stabilized at 20-30 kg / h, the entrainer isopropyl acetate is injected from the entrainer pump. After stabilizing the extraction for 120-160 min, the device valves are closed in sequence to stop the extraction. The amount of entrainer used is: W black aconite : L entrainer = 1 kg : 1.5-2 L. The pressure reduction refers to raising the temperature of solid B to 80-85℃, controlling the pressure at -0.1-0MPa, and maintaining the pressure for 20-30 minutes. The water washing refers to adding purified water to solid B, stirring for 20-40 minutes, filtering, and drying until the moisture content is less than 5%. The amount of purified water used is 3-5 times that of solid B. (3) Back extraction Prepare a hydrochloric acid solution with a pH of 3-4 using purified water; Hydrochloric acid solution was added to extract A for back-extraction, followed by liquid-liquid separation. The organic phase was collected, concentrated under reduced pressure, washed with water, and dried to obtain solid C. (4) Mixing and sieving The pitted Terminalia chebula, solid B, solid C, Costus root, and Acorus calamus were mixed and sieved to obtain mixture D; (5) Total Mixing Artificial musk and mixture D were divided into 5 portions and mixed in equal increments. After mixing, the mixture was sieved to obtain the raw powder of Five-Flavor Musk Pills. (6) Mixing, pelleting and drying Prepare a saturated aqueous solution of benzoin using purified water; Five-flavor musk pill raw powder and saturated aqueous solution of benzoin were fed into a fully automatic pill-making machine to obtain five-flavor musk pills, wherein the aconitine content of black aconite in the five-flavor musk pills was 0.3-0.5%.

2. The pharmaceutical composition according to claim 1, characterized in that... The crushing and sieving mentioned in step (1) refers to: using a crusher to crush each raw material and passing it through a 200m mesh sieve.

3. The pharmaceutical composition according to claim 1, characterized in that... In step (3), The amount of hydrochloric acid solution used is: VextractA : Vhydrochloric acid solution = 1L : 2-4L; The back extraction refers to mixing extract A with hydrochloric acid solution, heating the mixture to 40-45℃, stirring for 40-60 minutes, then letting it stand for 20-40 minutes to separate the liquid and collect the organic phase. The aforementioned vacuum concentration refers to pressure controlled at -0.1 to 0 MPa and temperature controlled at 82 to 86°C. The washing and drying process refers to adding purified water to the solid obtained by vacuum concentration, stirring for 20-40 minutes, filtering, and drying until the moisture content is less than 5%. The amount of purified water used is 3-5 times that of the solid.

4. The pharmaceutical composition according to claim 1, characterized in that... In step (5), sieving refers to passing through a 200m mesh sieve.

5. The use of the pharmaceutical composition according to any one of claims 1 to 4 in the preparation of anti-inflammatory, analgesic, and wind-dispelling drugs.