A pharmaceutical composition for treating gastric diseases, and a preparation method and use thereof

Abstract

The present application relates to a kind of pharmaceutical composition for treating stomach disease and its preparation method and purposes, and the pharmaceutical composition is made of myrobalan (roast), nutmeg, cardamom kernel, piper longum, agarwood, clove, five Lingzhi paste, safflower, pomegranate, papaya, saussurea, calcareous tufa, wing head grass, cold water stone (flat preparation).In the present application, nutmeg and clove are treated by using extraction, adsorption and other extraction methods, to reduce the content of toxic substances, to avoid the poisoning reaction of clean white capsule long-term use.

Description

Technical Field

[0001] This invention belongs to the field of Tibetan medicine technology, and specifically relates to a pharmaceutical composition for treating stomach diseases, its preparation method, and its uses. Background Technology

[0002] Jiebai Capsules are a traditional Chinese medicine made from a variety of Chinese medicinal herbs, including Terminalia chebula, nutmeg, cloves, safflower, and cardamom. They have the functions of strengthening the spleen and stomach, relieving pain and vomiting, and separating clear from turbid fluids. Clinically, they are often used to treat symptoms such as abdominal distension, stomach pain, indigestion, vomiting and diarrhea, and difficulty urinating.

[0003] The whitening capsules contain nutmeg, which contains 5%-15% volatile oil. This volatile oil contains toxic substances such as safrole (4%) and myristole (37.63%-47.06%), therefore, it has a certain central nervous system depressant effect. The median lethal dose (LD50) of nutmeg volatile oil administered orally to mice is [not specified]. 50 It is 7.67 g·kg －1 .

[0004] Researchers investigated the myristicin content in different processed forms of nutmeg. The results showed that the myristicin content in raw nutmeg was 0.215%, while the contents of the five processed forms (steamed, fried in flour, fried in wheat flour, baked with red ochre, and earthenware) were 0.211%, 0.210%, 0.205%, 0.203%, and 0.201%, respectively. The processing methods had little effect on the myristicin content, mainly because myristicin has a relatively high boiling point (276–277°C). The LD50 of myristicin in cats is 0.5–1.0 ml / kg, and 0.12 ml subcutaneously can cause extensive liver degeneration. Ingestion of 1.9 g / kg of nutmeg powder in cats can cause a semi-comatose state and death within 24 hours.

[0005] Safrole contained in the volatile oil can form carcinogenic substances in the liver, damaging hepatocytes and even inducing liver disease; the median lethal dose (LD50) of safrole volatile oil administered orally to rats is [not specified]. 50 1950 mg·kg －1 Currently, relevant domestic literature reports on reducing safrole content through processing techniques (the effect of optimizing the processing technique of nutmeg on safrole content in the Mongolian medicine Five Flavors of Nutmeg). Publicly available data show that the average safrole content decreased from 0.036% to 0.027%, an average reduction of 25%.

[0006] Domestic literature reports the use of various methods to extract the active ingredients from nutmeg, including processing, solvent extraction, steam distillation, microwave-assisted distillation, supercritical carbon dioxide extraction, and macroporous resin adsorption. These methods reduce the content of fatty oils and volatile oils in nutmeg, thus achieving degreasing and detoxification. However, these methods often have low extraction rates and are prone to damaging heat-sensitive substances. Furthermore, when using these methods to process nutmeg, no literature reports on how to handle the remaining residue after extraction, which contains a large amount of active substances (such as fatty oils, lignans, starch, protein, and small amounts of sucrose, xylooligosaccharides, pentosans, pigments, pectin, and saponins).

[0007] The chemical components of cloves mainly fall into two categories: volatile and non-volatile components. More than 320 volatile components have been reported in recent years, primarily including clove oil and eugenol; 91 non-volatile components have been identified, including flavonoids, steroids, triterpenoids, and tannins. Studies have shown that cloves have some effects on the human body, mainly due to the potential for poisoning from clove oil. The LD50 of clove oil... 50 The concentration of volatile oil was 5.5233 g / kg (equivalent to the LD50 of the raw medicinal material). 50 The concentration of crude drug was 43.5935 g / kg. Cloves possess a certain degree of toxicity, and their safety should be considered when developing medicinal applications. Currently, the main extraction methods for clove oil include steam distillation, organic solvent extraction, supercritical CO2 fluid extraction, microwave-assisted extraction, ultrasound-assisted extraction, and synergistic extraction. The main problems with traditional clove oil extraction methods are: long extraction time, high energy consumption, solvent residue in the product, low extraction efficiency, and decomposition of easily volatile elements. Supercritical fluid extraction is a rapid and selective technique for extracting volatile oils, but it has limitations due to its complex operation and high cost. There is no data to prove that using the above methods to process cloves can effectively reduce the toxic substances in cloves, and therefore, their rational use is questionable.

[0008] In conclusion, the whitening capsules contain nutmeg and cloves, and a side effect is that long-term use can lead to poisoning. Summary of the Invention

[0009] This invention aims to solve the technical problems existing in the prior art. To this end, this invention proposes a whitening capsule pharmaceutical composition, its preparation method, and its uses. By employing extraction methods such as soaking and adsorption, the content of toxic substances is reduced, avoiding poisoning reactions that may occur with long-term use of the whitening capsule.

[0010] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0011] The first aspect of this invention relates to a pharmaceutical composition for treating gastric ailments, made from the following parts by weight of active pharmaceutical ingredients:

[0012] Terminalia chebula (baked) 27.3%, nutmeg 3.5%, cardamom kernel 1.4%, amomum villosum 1.5%, agarwood 1.5%, clove 2.6%, five-spice powder 13.0%, safflower 0.6%, pomegranate seed 1.7%, papaya 1.7%, costus root 1.9%, travertine 1.1%, angelica dahurica 6.1%, gypsum (processed) 15.1%, refined honey 21.0%, of which:

[0013] The cloves contain ≤42.9% volatile oil.

[0014] The nutmeg contains ≤1.84% safrole.

[0015] The myristicin content in the nutmeg is ≤26%.

[0016] The present invention also provides a method for preparing the above-mentioned pharmaceutical composition, comprising the following steps:

[0017] (1) Grinding and sieving

[0018] First, the following ingredients are sifted to remove visible impurities: Terminalia chebula (baked), nutmeg, cardamom, agarwood, clove, safflower, pomegranate seeds, papaya, costus root, travertine, angelica, and gypsum (flattened). Then, they are crushed and sieved.

[0019] (2) Nutmeg processing

[0020] After crushing and sieving, the nutmeg is extracted and then separated into solid A and liquid B.

[0021] Liquid B was subjected to adsorption and desorption, vacuum concentration, drying, pulverization and sieving to obtain solid C;

[0022] Solid A and solid C are mixed and stirred until homogeneous;

[0023] (3) Clove treatment

[0024] After crushing and sieving, the cloves were extracted and then separated into solid and liquid components to obtain solid E and liquid F.

[0025] Liquid F was subjected to adsorption and desorption, vacuum concentration, drying, pulverization and sieving to obtain solid G;

[0026] Solid G and solid E are mixed and stirred until homogeneous;

[0027] (4) Mixing and drying

[0028] First, add the Five Spirits Paste to the refined honey and mix and stir; second, add each material in (1) (excluding nutmeg and cloves), the material in (2) and the material in (3) to the refined honey and mix and stir; finally, obtain the mixed solid H by vacuum drying.

[0029] (5) Grinding, sieving, and capsule preparation

[0030] After the mixed solid H is crushed and sieved, it is used to obtain white capsules using hollow capsules and capsule filling equipment.

[0031] The proportions of raw materials mentioned in step (1) are as follows: Terminalia chebula (baked) 27.3%, nutmeg 3.5%, Amomum tsao-ko kernel 1.4%, Amomum cardamomum 1.5%, agarwood 1.5%, clove 2.6%, Trogopterus xanthipes paste 13.0%, safflower 0.6%, pomegranate seed 1.7%, papaya 1.7%, costus root 1.9%, travertine 1.1%, angelica dahurica 6.1%, gypsum (processed) 15.1%, and refined honey 21.0%.

[0032] The crushing and sieving mentioned in step (1) refers to: using a crusher to crush each raw material and passing it through a 6mm sieve plate.

[0033] In step (2),

[0034] The extraction process involves adding 4-methyl-2-pentanone to nutmeg, heating to 50-60°C, stirring for 60-80 minutes, allowing the mixture to return to room temperature, and then letting it stand for 20-40 minutes to separate the solid and liquid components. The ratio of nutmeg to 4-methyl-2-pentanone is approximately 1 kg to 2-3 L.

[0035] The adsorption and desorption process refers to the following: a composite adsorbent is added to the chromatography column, the ratio of filtrate to adsorbent is 4:1 to 6:1, and the adsorption rate is 5 Bv / h; during the elution process, propanol is used for elution, and the elution rate is 3 Bv / h. The propanol eluent is collected, concentrated under reduced pressure to recover propanol, dried, pulverized, sieved, and passed through a 6 mm sieve plate to obtain solid C.

[0036] In step (3),

[0037] The extraction process involves adding cloves to 4-methyl-2-pentanone, heating to 70-80°C, stirring for 40-50 minutes, allowing the mixture to return to room temperature, and then letting it stand for 40-60 minutes to separate the solid and liquid components. The ratio of cloves to 4-methyl-2-pentanone is approximately 1 kg to 4-5 L.

[0038] The adsorption and desorption process refers to the following: a composite adsorbent is added to the chromatography column, the ratio of filtrate to adsorbent is 8:1 to 10:1, and the adsorption rate is 6 Bv / h; during the elution process, propanol is used for elution, and the elution rate is 4 Bv / h. The propanol eluent is collected, concentrated under reduced pressure to recover propanol, dried, pulverized, sieved, and passed through a 6 mm sieve plate to obtain solid G.

[0039] The composite adsorbent is prepared by first activating chloromethylated cross-linked polystyrene resin with a 20-30% hydrochloric acid solution; then dissolving chitosan in a 20-30% hydrochloric acid solution, followed by immersing the activated chloromethylated cross-linked polystyrene resin in the chitosan solution and stirring for 180-200 minutes; finally adjusting the pH to 8.3-8.5 with a 10-20% NaOH solution for curing, with the curing time controlled at 100-120 minutes; after curing, rinsing with deionized water 3-5 times; and finally drying to obtain the composite adsorbent.

[0040] Compatibility ratio:

[0041] W chloromethylated crosslinked polystyrene resin : L 20-30% hydrochloric acid solution = 1kg : 12-14L;

[0042] W chloromethylated crosslinked polystyrene resin: W chitosan = 1 kg : 0.8-1 kg;

[0043] W chitosan : L 20-30% hydrochloric acid solution = 1kg : 9-11L;

[0044] In step (4), the stirring time is controlled at 120-150 min.

[0045] In step (5), sieving refers to passing the crushed raw material through a 120-mesh sieve; the stirring time is controlled at 60-70 minutes.

[0046] 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 a drug for treating gastric diseases.

[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 a drug for treating gastritis.

[0048] The technical advantages of this invention are:

[0049] 1. Increased the median lethal concentration (LD50) and reduced the content of toxic substances.

[0050] Experiments have shown that untreated nutmeg administered orally to mice results in a median lethal dose (LD50). 50 It is 52.6 g·kg －1 Nutmeg processed using the process described in this patent was administered to mice via gavage. The median lethal dose (LD50) was... 50 It is 87.3 g·kg －1 According to the detection method for volatile oil of nutmeg in the Chinese Pharmacopoeia (Appendix XD), the volatile oil content of treated nutmeg was reduced to 1.9%-5.6%, with a maximum reduction of 64%. The safrole content in the volatile oil was reduced to below 1.84%; the myristole content was reduced to below 26%.

[0051] Experiments have shown that untreated cloves, administered orally to mice, have a median lethal dose (LD50). 50 It is 43.6 g·kg －1 When cloves processed using the process described in this patent were administered to mice via gavage, the median lethal dose (LD50) was... 50 It is 76.45 g·kg －1 According to the detection method for clove volatile oil in the Chinese Pharmacopoeia (Appendix XD), the average content of clove volatile oil decreased by 42.9%.

[0052] In summary, relevant domestic literature reports methods for treating nutmeg or cloves, including processing, steam distillation, solvent extraction, supercritical CO2 extraction, microwave-assisted extraction, and macroporous resin adsorption. However, the technical results show that:

[0053] (1) Using the processing technique, the safrole content in nutmeg decreased by 20%, but the effect of myristole was poor, and its content changed little. Other methods for extracting nutmeg in China have only reported the extraction method and changes in the concentration of key substances, without reporting the technical effects achieved by the changes in the content of myristole and safrole. Using the method described in this patent, the volatile oil content in the treated nutmeg decreased to 1.9%-5.6%, with a maximum reduction of 64%. The safrole content in the volatile oil decreased to below 1.84%; the myristole content decreased to below 26%.

[0054] (2) Domestic literature reports that the effective components of cloves can be extracted and utilized using steam distillation, organic solvent extraction, supercritical CO2 fluid extraction, microwave-assisted extraction, ultrasound-assisted extraction, and synergistic extraction. However, no method has been reported on how to reduce the content of toxic substances in cloves. Using the method described in this patent, the volatile oil content in the treated cloves decreased by an average of 42.9%, reducing the content of toxic substances and avoiding poisoning reactions caused by long-term use.

[0055] 2. Avoid poisoning reactions

[0056] The whitening capsules produced according to the method described in this patent can effectively remove oil and reduce toxicity. When taken according to the prescribed course of treatment, the whitening capsules can effectively prevent poisoning reactions. Specific implementation methods

[0057] 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.

[0058] Example 1

[0059] (1) Grinding and sieving

[0060] The ingredients for the Jiebai capsule are as follows: 27.3 kg of Terminalia chebula (baked), 3.5 kg of nutmeg, 1.4 kg of Amomum tsao-ko kernel, 1.5 kg of Amomum villosum, 1.5 kg of agarwood, 2.6 kg of cloves, 13.0 kg of Trogopterus xanthipes paste, 0.6 kg of safflower, 1.7 kg of pomegranate seeds, 1.7 kg of papaya, 1.9 kg of Aucklandia lappa, 1.1 kg of travertine, 6.1 kg of Lysimachia christinae, 15.1 kg of gypsum (processed), and 21.0 kg of refined honey.

[0061] First, the following ingredients are sifted to remove visible foreign matter: Terminalia chebula (baked), nutmeg, cardamom, agarwood, clove, safflower, pomegranate seeds, papaya, costus root, travertine, winged grass, and gypsum (flattened). Then, they are crushed and passed through a 6mm sieve.

[0062] (2) Nutmeg processing

[0063] Before processing, 3.5 kg of nutmeg was tested and found to contain 221.9 g of volatile oil, 8.87 g of safrole, and 84.10 g of myristicin.

[0064] 3.5 kg of nutmeg was added to 7 L of 4-methyl-2-pentanone, heated to 50 °C, stirred for 60 min, and after stirring was stopped, the mixture was allowed to return to room temperature and stand for 20 min. The solid and liquid were separated to obtain 6.9 L of solid A and liquid B.

[0065] 1.7 kg of composite adsorbent was added to the chromatography column, and the adsorption rate of liquid B was 5 Bv / h. During the elution process, propanol was used for elution, and the elution rate was 3 Bv / h. The propanol eluent was collected, concentrated under reduced pressure to recover propanol, dried, pulverized, sieved, and passed through a 6 mm sieve plate to obtain solid C.

[0066] Solid A was concentrated under reduced pressure and dried, then mixed with solid C to obtain 3.46 kg of nutmeg-treated product.

[0067] The nutmeg-treated product contained 81.4g of volatile oil, 4.36g of safrole, and 40.45g of myristole.

[0068] (3) Clove treatment

[0069] The clove oil content of 2.6 kg of untreated cloves was 410.8 g.

[0070] 10.5 L of 4-methyl-2-pentanone was added to cloves, the temperature was raised to 70 °C, and the mixture was stirred for 40 min. After stirring, the mixture was allowed to return to room temperature and stand for 40 min. Solid-liquid separation was performed to obtain 10.4 L of solid E and liquid F.

[0071] 1.3 kg of composite adsorbent was added to the chromatography column, and the adsorption rate of liquid F was 6 Bv / h. During the elution process, propanol was used for elution, and the elution rate was 4 Bv / h. The propanol eluent was collected, concentrated under reduced pressure to recover propanol, dried, pulverized, sieved, and passed through a 6 mm sieve plate to obtain solid G.

[0072] Solid E was concentrated under reduced pressure and dried, then mixed with solid G to obtain 2.41 kg of clove-treated material.

[0073] Tests showed that the clove-treated material contained 217.7g of volatile oil.

[0074] (4) Mixing and drying

[0075] First, add the Five Spirits Paste to the refined honey and mix and stir. Second, add each material in (1) (excluding nutmeg and cloves), the material in (2) and the material in (3) to the refined honey and mix and stir for 120 minutes. Finally, control the vacuum degree at -0.05-0.1MPa, control the temperature at 80-100℃, and dry for 20-30 minutes to obtain the mixed solid H.

[0076] (5) Grinding, sieving, and mixing

[0077] After the mixed solid H was crushed, it was passed through a 120-mesh sieve and weighed 99.2 kg.

[0078] (6) Preparation of capsules

[0079] White capsules were prepared using empty capsules and capsule filling equipment, with a capsule weight of 0.4g / capsule.

[0080] Example 2

[0081] (1) Grinding and sieving

[0082] The ingredients for the Jiebai capsule are as follows: 27.3 kg of Terminalia chebula (baked), 3.5 kg of nutmeg, 1.4 kg of Amomum tsao-ko kernel, 1.5 kg of Amomum villosum, 1.5 kg of agarwood, 2.6 kg of cloves, 13.0 kg of Trogopterus xanthipes paste, 0.6 kg of safflower, 1.7 kg of pomegranate seeds, 1.7 kg of papaya, 1.9 kg of Aucklandia lappa, 1.1 kg of travertine, 6.1 kg of Lysimachia christinae, 15.1 kg of gypsum (processed), and 21.0 kg of refined honey.

[0083] First, the following ingredients are sifted to remove visible foreign matter: Terminalia chebula (baked), nutmeg, cardamom, agarwood, clove, safflower, pomegranate seeds, papaya, costus root, travertine, winged grass, and gypsum (flattened). Then, they are crushed and passed through a 6mm sieve.

[0084] (2) Nutmeg processing

[0085] Before processing, 3.5 kg of nutmeg was tested and found to contain 221.9 g of volatile oil, 8.87 g of safrole, and 84.10 g of myristicin.

[0086] Add 3.5 kg of nutmeg to 7.7 L of 4-methyl-2-pentanone, heat to 53 °C, stir for 65 min, after stirring, return to room temperature, let stand for 25 min, and then separate the solid and liquid to obtain 7.6 L of solid A and liquid B.

[0087] 1.8 kg of composite adsorbent was added to the chromatography column, and the adsorption rate of liquid B was 5 Bv / h. During the elution process, propanol was used for elution, and the elution rate was 3 Bv / h. The propanol eluent was collected, concentrated under reduced pressure to recover propanol, dried, pulverized, sieved, and passed through a 6 mm sieve plate to obtain solid C.

[0088] Solid A was concentrated under reduced pressure and dried, then mixed with solid C to obtain 3.45 kg of nutmeg-treated product.

[0089] The nutmeg-treated product contained 80.1g of volatile oil, 4.13g of safrole, and 39.04g of myristole.

[0090] (3) Clove treatment

[0091] The clove oil content of 2.6 kg of untreated cloves was 410.8 g.

[0092] 11.2 L of 4-methyl-2-pentanone was added to cloves, the temperature was raised to 73 °C, and the mixture was stirred for 42 min. After stirring, the mixture was allowed to return to room temperature and stand for 45 min. Solid-liquid separation was performed to obtain 11.1 L of solid E and liquid F.

[0093] 1.3 kg of composite adsorbent was added to the chromatography column, and the adsorption rate of liquid F was 6 Bv / h. During the elution process, water was first used for elution at a rate of 4 Bv / h, and then propanol was used for elution at a rate of 4 Bv / h. The propanol eluent was collected, concentrated under reduced pressure to recover propanol, dried, pulverized, sieved, and passed through a 6 mm sieve to obtain solid G.

[0094] Solid E was concentrated under reduced pressure and dried, then mixed with solid G to obtain 2.39 kg of clove-treated material.

[0095] The clove-treated material was found to contain 215.1g of volatile oil.

[0096] (4) Mixing and drying

[0097] First, add the Five Spirits Paste to the refined honey and mix and stir. Second, add each material in (1) (excluding nutmeg and cloves), the material in (2) and the material in (3) to the refined honey and mix and stir for 120 minutes. Finally, control the vacuum degree at -0.05-0.1MPa, control the temperature at 80-100℃, and dry for 20-30 minutes to obtain the mixed solid H.

[0098] (5) Grinding, sieving, and mixing

[0099] After the mixed solid H was crushed, it was passed through a 120-mesh sieve and weighed 99.1 kg.

[0100] (6) Preparation of capsules

[0101] White capsules were prepared using empty capsules and capsule filling equipment, with a capsule weight of 0.4g / capsule.

[0102] Example 3

[0103] (1) Grinding and sieving

[0104] The ingredients for the Jiebai capsule are as follows: 27.3 kg of Terminalia chebula (baked), 3.5 kg of nutmeg, 1.4 kg of Amomum tsao-ko kernel, 1.5 kg of Amomum villosum, 1.5 kg of agarwood, 2.6 kg of cloves, 13.0 kg of Trogopterus xanthipes paste, 0.6 kg of safflower, 1.7 kg of pomegranate seeds, 1.7 kg of papaya, 1.9 kg of Aucklandia lappa, 1.1 kg of travertine, 6.1 kg of Lysimachia christinae, 15.1 kg of gypsum (processed), and 21.0 kg of refined honey.

[0105] First, the following ingredients are sifted to remove visible foreign matter: Terminalia chebula (baked), nutmeg, cardamom, agarwood, clove, safflower, pomegranate seeds, papaya, costus root, travertine, winged grass, and gypsum (flattened). Then, they are crushed and passed through a 6mm sieve.

[0106] (2) Nutmeg processing

[0107] Before processing, 3.5 kg of nutmeg was tested and found to contain 221.9 g of volatile oil, 8.87 g of safrole, and 84.10 g of myristicin.

[0108] Add 3.5 kg of nutmeg to 8.8 L of 4-methyl-2-pentanone, heat to 55 °C, stir for 70 min, after stirring, return to room temperature, let stand for 30 min, and then separate the solid and liquid to obtain 8.7 L of solid A and liquid B respectively.

[0109] 1.7 kg of composite adsorbent was added to the chromatography column, and the adsorption rate of liquid B was 5 Bv / h. During the elution process, propanol was used for elution, and the elution rate was 3 Bv / h. The propanol eluent was collected, concentrated under reduced pressure to recover propanol, dried, pulverized, sieved, and passed through a 6 mm sieve plate to obtain solid C.

[0110] Solid A was concentrated under reduced pressure and dried, then mixed with solid C to obtain 3.43 kg of nutmeg-treated product.

[0111] The nutmeg-treated product contained 78.3g of volatile oil, 3.76g of safrole, and 37.57g of myristole.

[0112] (3) Clove treatment

[0113] The clove oil content of 2.6 kg of untreated cloves was 410.8 g.

[0114] 11.7 L of 4-methyl-2-pentanone was added to cloves, the temperature was raised to 75 °C, and the mixture was stirred for 45 min. After stirring, the mixture was allowed to return to room temperature and stand for 50 min. Solid-liquid separation was performed to obtain 11.6 L of solid E and liquid F.

[0115] 1.28 kg of composite adsorbent was added to the chromatography column, and the adsorption rate of liquid F was 6 Bv / h. During the elution process, water was first used for elution at a rate of 4 Bv / h, followed by elution with propanol at a rate of 4 Bv / h. The propanol eluent was collected, concentrated under reduced pressure to recover propanol, dried, pulverized, sieved, and passed through a 6 mm sieve to obtain solid G.

[0116] Solid E was concentrated under reduced pressure and dried, then mixed with solid G to obtain 2.31 kg of clove-treated material.

[0117] The clove-treated material was found to contain 209.4g of volatile oil.

[0118] (4) Mixing and drying

[0119] First, add the Five Spirits Paste to the refined honey and mix and stir. Second, add each material in (1) (excluding nutmeg and cloves), the material in (2) and the material in (3) to the refined honey and mix and stir for 120 minutes. Finally, control the vacuum degree at -0.05-0.1MPa, control the temperature at 80-100℃, and dry for 20-30 minutes to obtain the mixed solid H.

[0120] (5) Grinding, sieving, and mixing

[0121] After the mixed solid H was crushed, it was passed through a 120-mesh sieve and weighed 99.0 kg.

[0122] (6) Preparation of capsules

[0123] White capsules were prepared using empty capsules and capsule filling equipment, with a capsule weight of 0.4g / capsule.

[0124] Example 4

[0125] (1) Grinding and sieving

[0126] The ingredients for the Jiebai capsule are as follows: 27.3 kg of Terminalia chebula (baked), 3.5 kg of nutmeg, 1.4 kg of Amomum tsao-ko kernel, 1.5 kg of Amomum villosum, 1.5 kg of agarwood, 2.6 kg of cloves, 13.0 kg of Trogopterus xanthipes paste, 0.6 kg of safflower, 1.7 kg of pomegranate seeds, 1.7 kg of papaya, 1.9 kg of Aucklandia lappa, 1.1 kg of travertine, 6.1 kg of Lysimachia christinae, 15.1 kg of gypsum (processed), and 21.0 kg of refined honey.

[0127] First, the following ingredients are sifted to remove visible foreign matter: Terminalia chebula (baked), nutmeg, cardamom, agarwood, clove, safflower, pomegranate seeds, papaya, costus root, travertine, winged grass, and gypsum (flattened). Then, they are crushed and passed through a 6mm sieve.

[0128] (2) Nutmeg processing

[0129] Before processing, 3.5 kg of nutmeg was tested and found to contain 221.9 g of volatile oil, 8.87 g of safrole, and 84.10 g of myristicin.

[0130] Add 3.5 kg of nutmeg to 9.8 L of 4-methyl-2-pentanone, heat to 57 °C, stir for 75 min, after stirring, return to room temperature, let stand for 35 min, and then separate the solid and liquid to obtain 9.7 L of solid A and liquid B respectively.

[0131] 1.8 kg of composite adsorbent was added to the chromatography column, and the adsorption rate of liquid B was 5 Bv / h. During the elution process, propanol was used for elution, and the elution rate was 3 Bv / h. The propanol eluent was collected, concentrated under reduced pressure to recover propanol, dried, pulverized, sieved, and passed through a 6 mm sieve plate to obtain solid C.

[0132] Solid A was concentrated under reduced pressure and dried, then mixed with solid C to obtain 3.43 kg of nutmeg-treated product.

[0133] The nutmeg-treated product contained 78.9g of volatile oil, 3.89g of safrole, and 38.03g of myristole.

[0134] (3) Clove treatment

[0135] The clove oil content of 2.6 kg of untreated cloves was 410.8 g.

[0136] 12.5 L of 4-methyl-2-pentanone was added to cloves, the temperature was raised to 77 °C, and the mixture was stirred for 48 min. After stirring, the mixture was allowed to return to room temperature and stand for 55 min. Solid-liquid separation was performed to obtain 12.4 L of solid E and liquid F.

[0137] 1.3 kg of composite adsorbent was added to the chromatography column, and the adsorption rate of liquid F was 6 Bv / h. During the elution process, water was first used for elution at a rate of 4 Bv / h, and then propanol was used for elution at a rate of 4 Bv / h. The propanol eluent was collected, concentrated under reduced pressure to recover propanol, dried, pulverized, sieved, and passed through a 6 mm sieve to obtain solid G.

[0138] Solid E was concentrated under reduced pressure and dried, then mixed with solid G to obtain 2.32 kg of clove-treated material.

[0139] The clove-treated material was found to contain 211.7g of volatile oil.

[0140] (4) Mixing and drying

[0141] First, add the Five Spirits Paste to the refined honey and mix and stir. Second, add each material in (1) (excluding nutmeg and cloves), the material in (2) and the material in (3) to the refined honey and mix and stir for 120 minutes. Finally, control the vacuum degree at -0.05-0.1MPa, control the temperature at 80-100℃, and dry for 20-30 minutes to obtain the mixed solid H.

[0142] (5) Grinding, sieving, and mixing

[0143] After the mixed solid H was crushed, it was passed through a 120-mesh sieve and weighed 99.2 kg.

[0144] (6) Preparation of capsules

[0145] White capsules were prepared using empty capsules and capsule filling equipment, with a capsule weight of 0.4g / capsule.

[0146] Example 5

[0147] (1) Grinding and sieving

[0148] The ingredients for the Jiebai capsule are as follows: 27.3 kg of Terminalia chebula (baked), 3.5 kg of nutmeg, 1.4 kg of Amomum tsao-ko kernel, 1.5 kg of Amomum villosum, 1.5 kg of agarwood, 2.6 kg of cloves, 13.0 kg of Trogopterus xanthipes paste, 0.6 kg of safflower, 1.7 kg of pomegranate seeds, 1.7 kg of papaya, 1.9 kg of Aucklandia lappa, 1.1 kg of travertine, 6.1 kg of Lysimachia christinae, 15.1 kg of gypsum (processed), and 21.0 kg of refined honey.

[0149] First, the following ingredients are sifted to remove visible foreign matter: Terminalia chebula (baked), nutmeg, cardamom, agarwood, clove, safflower, pomegranate seeds, papaya, costus root, travertine, winged grass, and gypsum (flattened). Then, they are crushed and passed through a 6mm sieve.

[0150] (2) Nutmeg processing

[0151] Before processing, 3.5 kg of nutmeg was tested and found to contain 221.9 g of volatile oil, 8.87 g of safrole, and 84.10 g of myristicin.

[0152] 3.5 kg of nutmeg was added to 10.5 L of 4-methyl-2-pentanone, heated to 60 °C, stirred for 80 min, and after stirring was stopped, the mixture was allowed to return to room temperature and stand for 40 min. The solid and liquid were separated to obtain 10.4 L of solid A and liquid B, respectively.

[0153] 1.7 kg of composite adsorbent was added to the chromatography column, and the adsorption rate of liquid B was 5 Bv / h. During the elution process, propanol was used for elution, and the elution rate was 3 Bv / h. The propanol eluent was collected, concentrated under reduced pressure to recover propanol, dried, pulverized, sieved, and passed through a 6 mm sieve plate to obtain solid C.

[0154] Solid A was concentrated under reduced pressure and dried, then mixed with solid C to obtain 3.51 kg of nutmeg-treated product.

[0155] The nutmeg-treated product contained 79.6g of volatile oil, 3.97g of safrole, and 39.07g of myristole.

[0156] (3) Clove treatment

[0157] The clove oil content of 2.6 kg of untreated cloves was 410.8 g.

[0158] 13 L of 4-methyl-2-pentanone was added to cloves, the temperature was raised to 80 °C, and the mixture was stirred for 50 min. After stirring, the mixture was allowed to return to room temperature and stand for 60 min. Solid-liquid separation was performed to obtain 12.9 L of solid E and liquid F.

[0159] 1.29 kg of composite adsorbent was added to the chromatography column, and the adsorption rate of liquid F was 6 Bv / h. During the elution process, water was first used for elution at a rate of 4 Bv / h, followed by elution with propanol at a rate of 4 Bv / h. The propanol eluent was collected, concentrated under reduced pressure to recover propanol, dried, pulverized, sieved, and passed through a 6 mm sieve to obtain solid G.

[0160] Solid E was concentrated under reduced pressure and dried, then mixed with solid G to obtain 2.37 kg of clove-treated material.

[0161] The clove-treated material was found to contain 212.4g of volatile oil.

[0162] (4) Mixing and drying

[0163] First, add the Five Spirits Paste to the refined honey and mix and stir. Second, add each material in (1) (excluding nutmeg and cloves), the material in (2) and the material in (3) to the refined honey and mix and stir for 120 minutes. Finally, control the vacuum degree at -0.05-0.1MPa, control the temperature at 80-100℃, and dry for 20-30 minutes to obtain the mixed solid H.

[0164] (5) Grinding, sieving, and mixing

[0165] After the mixed solid H was crushed, it was passed through a 120-mesh sieve and weighed 99.1 kg.

[0166] (6) Preparation of capsules

[0167] White capsules were prepared using empty capsules and capsule filling equipment, with a capsule weight of 0.4g / capsule.

[0168] Example 6

[0169] Pharmacological experiment content: The whitening capsules prepared in this invention have a preventive and therapeutic effect on gastritis in animals.

[0170] 1. Materials

[0171] 1.1 Drug: Jiebai Capsules.

[0172] 1.2 Animals: Rats, weighing 210–240 g.

[0173] 2. Methods and Results

[0174] 2.1 Method

[0175] One hundred rats, weighing 210–240 g (both male and female), were used. Except for 10 rats in the normal control group, the remaining animals were given 0.9 g / L methimazole aqueous solution as drinking water for 6 consecutive weeks. They were then randomly divided into a model group (no drug administration), a control group (10 g / kg) of the Jiebai capsule, and an experimental group (10 g / kg) of the product of this invention (Example 1), administered by gavage twice daily for 2 consecutive weeks. The normal control group was administered 0.2 ml / 10 g of physiological saline by gavage. Methimazole aqueous solution was continued to be administered during the drug administration period. Mice were fasted for 12 hours, euthanized by cervical dislocation, and their stomach tissue was removed by laparotomy. The stomach was cut along the greater curvature, and changes in the gastric mucosa were observed macroscopically. The tissue was fixed in 3.45 mol / L formaldehyde solution, routinely embedded in paraffin, sectioned, stained with hematoxylin and eosin (HE), and observed under a light microscope.

[0176] 2.2 Criteria for Lesion Diagnosis and Scoring Method:

[0177] ①Inflammatory cell infiltration: "+" indicates a few scattered inflammatory cells on the surface or bottom of the gastric mucosa; "++" indicates a large number of inflammatory cells in all layers of the mucosa.

[0178] ② Hyperplasia: "+" indicates that the glandular structure is slightly irregular, disordered or unevenly spaced; "++" indicates that the glandular structure is irregular, of irregular size and shape, branched, and tightly arranged.

[0179] ③ Degeneration and interstitial congestion and edema: "+" indicates scattered lesions, and "++" indicates focal lesions. Inflammatory cell infiltration "+" and "++" are scored as 2 and 4 points respectively, while degeneration, hyperplasia, and interstitial congestion and edema are scored as 1 and 2 points respectively according to the degree of lesion. The sum of the lesion scores for each animal is the animal's lesion score.

[0180] 3 Results

[0181] Gross observation revealed mild congestion and edema, along with a small amount of mucus exudation, in the pyloric region of the lesser curvature of the stomach in the model group. No obvious lesions were observed in the other groups. Histological examination showed no obvious lesions in the normal group, while the gastric mucosa in the other groups showed varying degrees of inflammatory cell infiltration, mucosal epithelial degeneration and hyperplasia, and interstitial congestion and edema, but no obvious gastric mucosal atrophy or intestinal metaplasia. The above lesions were most pronounced in the model group, and the lesions were significantly reduced in the treatment groups. There were no significant differences among the treatment groups.

[0182] Histomorphological effects of control and experimental groups on methimazole-induced superficial gastritis in mice

[0183]

[0184] 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).

[0185] After two weeks of administration, the control and experimental groups showed significant reduction in gastric mucosal atrophy and inflammation in the model rats, and increased gastric acid and digestive enzyme activity.

[0186] The control group (Jiebai capsules) had the same dosage as the product described in this patent, and their protective effect against gastric mucosal atrophy and inflammation was comparable. This indicates that the Jiebai capsules prepared in this invention have the same efficacy as traditional Jiebai capsules.

Claims

1. A pharmaceutical composition for treating stomach ailments, comprising the following parts by weight of active pharmaceutical ingredients: Prepared Terminalia chebula 27.3%, nutmeg 3.5%, cardamom kernel 1.4%, amomum villosum 1.5%, agarwood 1.5%, clove 2.6%, five-spice powder 13.0%, safflower 0.6%, pomegranate seed 1.7%, papaya 1.7%, costus root 1.9%, travertine 1.1%, winged clover 6.1%, processed gypsum 15.1%, refined honey 21.0%. The method for preparing the pharmaceutical composition includes the following process steps: (1) Grinding and sieving First, the following ingredients are sifted through a primary sieve to remove visible impurities: chebula, nutmeg, cardamom, agarwood, clove, safflower, pomegranate seeds, papaya, costus root, travertine, winged grass, and flat-processed calcite. Then, they are crushed and sieved again. (2) Nutmeg processing After being crushed and sieved, nutmeg was extracted, and solid-liquid separation was performed to obtain solid A and liquid B. Liquid B was subjected to adsorption and desorption, vacuum concentration, drying, pulverization, and sieving to obtain solid C; Solid A and solid C are mixed and stirred until homogeneous; In step (2), the extraction refers to: adding 4-methyl-2-pentanone to nutmeg, heating to 50-60℃, stirring for 60-80 min, stopping the stirring, restoring to room temperature, standing for 20-40 min, and separating the solid and liquid. The addition ratio is: W nutmeg: L 4-methyl-2-pentanone = 1 kg: 2-3 L. The adsorption and desorption refers to: adding a composite adsorbent to the chromatography column, with the ratio of filtrate to adsorbent being 4:1 to 6:1, and the adsorption rate being 5 Bv / h. During the elution process, propanol is used for elution, and the elution rate is 3 Bv / h. The propanol eluent is collected, concentrated under reduced pressure to recover propanol, dried, pulverized, sieved, and passed through a 6 mm sieve plate to obtain solid C. (3) Clove treatment After being crushed and sieved, cloves were extracted, and solid-liquid separation was performed to obtain solid E and liquid F. Liquid F was subjected to adsorption and desorption, vacuum concentration, drying, pulverization and sieving to obtain solid G; Solid G and solid E are mixed and stirred until homogeneous; In step (3), the extraction refers to: adding clove to 4-methyl-2-pentanone, heating to 70-80℃, stirring for 40-50 min, stopping the stirring, restoring to room temperature, standing for 40-60 min, and separating the solid and liquid. The addition ratio is: W clove: L 4-methyl-2-pentanone = 1 kg: 4-5 L. The adsorption and desorption refers to: adding a composite adsorbent to the chromatography column, with the ratio of filtrate to adsorbent being 8:1 to 10:1, and the adsorption rate being 6 Bv / h. During the elution process, propanol is used for elution, and the elution rate is 4 Bv / h. The propanol eluent is collected, concentrated under reduced pressure to recover propanol, dried, pulverized, sieved, and passed through a 6 mm sieve plate to obtain solid G. (4) Mixing and drying First, add the Five Spirits Paste to the refined honey and mix. Second, add the materials (excluding nutmeg and cloves) from (1), the materials from (2), and the materials from (3) to the refined honey and mix. Finally, vacuum dry to obtain a mixed solid H. (5) Grinding, sieving, and capsule preparation After the mixed solid H is crushed and sieved, it is used to obtain white capsules using empty capsules and capsule filling equipment; in: The composite adsorbent is prepared by first activating chloromethylated cross-linked polystyrene resin with a 20-30% hydrochloric acid solution; then dissolving chitosan in a 20-30% hydrochloric acid solution, followed by immersing the activated chloromethylated cross-linked polystyrene resin in the chitosan solution and stirring for 180-200 minutes; finally adjusting the pH to 8.3-8.5 with a 10-20% NaOH solution and curing for 100-120 minutes; after curing, rinsing with deionized water 3-5 times; and finally drying to obtain the composite adsorbent. The compatibility ratio is: W-chloromethylated crosslinked polystyrene resin: L20-30% hydrochloric acid solution = 1kg: 12-14L; Wchloromethylated cross-linked polystyrene resin: Wchitosan = 1 kg : 0.8-1 kg; W chitosan: L20-30% hydrochloric acid solution = 1kg: 9-11L.

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 6mm sieve plate.

3. The pharmaceutical composition according to claim 1, characterized in that... In step (4), the stirring time is controlled at 120-150 min.

4. The pharmaceutical composition according to claim 1, characterized in that... In step (5), sieving refers to passing the crushed raw material through a 120-mesh sieve; the stirring time is controlled at 60-70 minutes.

5. Use of the pharmaceutical composition according to any one of claims 1-4 in the preparation of a medicament for treating gastritis.

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