Traditional Chinese medicine preparation for treating chronic gastropathy and preparation method thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and particularly discloses a traditional Chinese medicine preparation for treating chronic gastropathy and a preparation method thereof. The traditional Chinese medicine preparation is prepared from the following raw materials in parts by mass: 7-11 parts of rhizoma pinellinae praeparata, 7-11 parts of rhizoma zingiberis, 8-12 parts of wine-processed radix scutellariae, 4-6 parts of wine-processed rhizoma coptidis, 13-17 parts of radix sophorae flavescentis, 4-8 parts of radix aucklandiae, 1-8 parts of fructus amomi, 13-17 parts of salvia miltiorrhiza, 8-12 parts of cuttle bone, 10-14 parts of scorched hawthorn fruit, 13-17 parts of fried rice sprout, 13-17 parts of fried malt, 4-8 parts of honey-fried licorice root and 8-12 parts of Chinese date. On the basis of keeping the cold and heat of the pinellia ternate heart-fire purging decoction and regulating the core, through the innovation of medicine pair compatibility, the decoction is especially suitable for complex syndromes of intermingled cold and heat, mingled deficiency and excess, accompanied by qi stagnation and blood stasis and indigestion of food retention in modern chronic gastrointestinal diseases.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and in particular relates to a traditional Chinese medicine preparation for treating chronic gastropathy and a preparation method thereof. Background Art

[0002] Chronic gastropathy is a common digestive system disease with a high incidence rate, and its incidence rate increases with age. Chronic gastropathy is a chronic inflammation of the gastric mucosa caused by various reasons, characterized by infiltration of lymphocytes and plasma cells. Clinically, most chronic gastropathy has no obvious symptoms, and some have symptoms of indigestion, including upper abdominal fullness and discomfort, especially irregular upper abdominal pain, belching, acid reflux, vomiting, etc. after meals. The onset factors of chronic gastropathy are complex and are related to factors such as diet, tobacco and alcohol stimulation, bacterial infection, and drug stimulation. Currently, Western medicine mainly treats it by suppressing acid, inhibiting bacteria, and protecting the gastric mucosa. However, Western medicine treatment has the limitations of long medication time, strong toxic side effects, and easy drug resistance. Currently, traditional Chinese medicine has a good effect in treating chronic gastropathy. Traditional Chinese medicine can treat it according to the principle of syndrome differentiation and treatment based on the patient's specific symptoms and constitution, thereby improving efficacy and reducing adverse reactions.

[0003] Banxia Xiexin Decoction (Pinellia ternata, Coptis chinensis, Scutellaria baicalensis, dried ginger, licorice, jujube, and ginseng) is a common prescription for regulating the ascending and descending of the spleen and stomach. It has the effects of harmonizing the liver and spleen, balancing cold and heat, and dispersing lumps and knots. It is commonly used clinically to treat patients with weak middle qi, such as acute and chronic gastroenteritis, chronic colitis, chronic hepatitis, and early-stage liver cirrhosis. However, in modern chronic gastrointestinal diseases, which present with complex syndromes characterized by a mixture of cold and heat, deficiency and excess, as well as qi stagnation, blood stasis, and indigestion, traditional Banxia Xiexin Decoction is not ideally suited. Summary of the Invention

[0004] In view of this, the purpose of the present invention is to provide a traditional Chinese medicine preparation for treating chronic gastropathy and a preparation method thereof. On the basis of maintaining the core function of Banxia Xiexin Decoction in regulating cold and heat, through innovative drug pairing, the preparation method is particularly suitable for the complex syndromes of modern chronic gastrointestinal diseases with mixed cold and heat, mixed deficiency and excess, and accompanied by qi stagnation, blood stasis, and indigestion.

[0005] The invention provides a traditional Chinese medicine preparation for treating chronic gastropathy. The traditional Chinese medicine preparation is prepared from the following raw materials in parts by mass: 7-11 parts of French pinellia, 7-11 parts of dried ginger, 8-12 parts of wine-soaked scutellaria, 4-6 parts of wine-soaked coptis, 13-17 parts of codonopsis pilosula, 4-8 parts of costus root, 1-8 parts of amomum villosum, 13-17 parts of salvia miltiorrhiza, 8-12 parts of cuttlefish bone, 10-14 parts of charred hawthorn, 13-17 parts of stir-fried rice sprouts, 13-17 parts of stir-fried malt, 4-8 parts of roasted liquorice and 8-12 parts of jujube.

[0006] Furthermore, the Chinese medicine preparation is prepared from the following raw materials in parts by mass: 9 parts of French pinellia, 9 parts of dried ginger, 10 parts of wine-soaked scutellaria, 5 parts of wine-soaked coptis, 15 parts of codonopsis pilosula, 6 parts of costus root, 6 parts of amomum villosum, 15 parts of salvia miltiorrhiza, 10 parts of cuttlefish bone, 12 parts of charred hawthorn, 15 parts of fried rice sprouts, 15 parts of fried malt, 6 parts of roasted licorice and 10 parts of jujube.

[0007] Furthermore, the raw materials are weighed and mixed according to the aforementioned mass fractions, soaked in water, decocted, and filtered to obtain an extract, which is then combined with excipients to form a specific dosage form.

[0008] Furthermore, the amount of water used is 6 to 10 times the total weight of the raw material.

[0009] Furthermore, the amount of water used is 8 times the total weight of the raw material.

[0010] Furthermore, the soaking time is 70 to 100 minutes, and the decoction time is 30 to 60 minutes.

[0011] Furthermore, the decoction time is 30 minutes.

[0012] Furthermore, the decoction is performed 3 times.

[0013] Furthermore, the auxiliary materials include steviol glycoside as steviol glycoside and / or potassium sorbate as a preservative, the dosage of steviol glycoside is 0.3g / 200mL, and the dosage of potassium sorbate is 0.2%.

[0014] Furthermore, the preparation is an oral preparation with a volume of 200 mL and a pH controlled at 4.5 to 6.0.

[0015] Compared with the prior art, the present invention has the following beneficial technical effects:

[0016] The present invention provides a traditional Chinese medicine preparation for treating chronic gastropathy. Aiming at the complex pathogenesis of modern spleen and stomach diseases, the traditional Banxia Xiexin Decoction is improved. On the basis of maintaining the core function of Banxia Xiexin Decoction in both cold and heat regulation, the multi-target treatment system of "clearing heat and removing dampness - promoting qi and eliminating stagnation - reducing acid and protecting the membrane - activating blood circulation and unblocking meridians" is formed through innovative drug pair compatibility. The preparation is particularly suitable for the complex syndromes of modern chronic gastrointestinal diseases with mixed cold and heat, mixed deficiency and excess, and accompanied by qi stagnation, blood stasis, and indigestion, and brings about a synergistic and synergistic effect.

[0017] The present invention also provides a preparation method for treating chronic gastropathy, which can increase the content of active ingredients in the preparation, reduce the amount of medicine taken, and reduce the carrying volume. The preparation process is reasonable, the production is simple, the cost is economical, and the stability is good, providing guidance for further development of the preparation.

[0018] Advantages of additional aspects of the present invention will be given in part in the following description and in part will be obvious from the following description, or will be learned through practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] The accompanying drawings, which constitute a part of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their description are used to explain the present invention but do not constitute a limitation of the present invention.

[0020] Figure 1 This is the chromatogram of the baicalin reference substance in Example 2;

[0021] Figure 2 This is the chromatogram of the test sample of the mixture in Example 2;

[0022] Figure 3 This is the negative control chromatogram in Example 2;

[0023] Figure 4 This is the baicalin standard curve in Example 2;

[0024] Figure 5 This is a graph showing the thin layer chromatography results of Pinellia ternata, dried ginger, Scutellaria baicalensis prepared with wine, and Coptis chinensis prepared with wine in Example 2;

[0025] Figure 6 This is a diagram showing the pH value investigation results in Example 2. DETAILED DESCRIPTION

[0026] In order to enable those skilled in the art to better understand the technical solution of the present invention, the present invention is further described in detail below with reference to the accompanying drawings and specific embodiments.

[0027] Example 1

[0028] This embodiment provides a traditional Chinese medicine preparation for treating chronic gastropathy, which is prepared from the following raw materials in parts by mass: 9 parts of Pinellia ternata, 9 parts of dried ginger, 10 parts of Scutellaria baicalensis wine, 5 parts of Coptis chinensis wine, 15 parts of Codonopsis pilosula, 6 parts of costus root, 6 parts of Amomum villosum, 15 parts of Salvia miltiorrhiza, 10 parts of cuttlefish bone, 12 parts of charred hawthorn, 15 parts of fried rice sprouts, 15 parts of fried malt, 6 parts of roasted liquorice, and 10 parts of jujube.

[0029] The preparation method of the traditional Chinese medicine preparation is as follows: weighing and mixing the raw materials according to the aforementioned mass fractions, soaking in water, decocting, filtering to obtain an extract, and combining the extract with auxiliary materials to process into a specific dosage form.

[0030] Among them, the amount of water used is 8 times the total weight of the raw material.

[0031] The soaking time can be 70 to 100 minutes, and the decoction time is 30 minutes.

[0032] The decoction is performed 3 times.

[0033] The auxiliary materials include steviol glycoside as a stevioside and / or potassium sorbate as a preservative. The dosage of steviol glycoside is 0.3 g / 200 mL, and the dosage of potassium sorbate is 0.2%.

[0034] The preparation is an oral preparation with a volume of 200 mL and a pH controlled at 4.5 to 6.0.

[0035] The Chinese medicine preparation is made of French pinellia, roasted ginger, scutellaria, coptis, codonopsis, costus root, amomum villosum, salvia miltiorrhiza, cuttlefish bone, charred hawthorn, stir-fried barley sprout, stir-fried malt, jujube, and roasted liquorice; the French pinellia in the formula is bitter and pungent, and is used to disperse the stagnation and eliminate the abdominal distension, while the bitterness descends to harmonize the stomach and stop vomiting as the main medicine; the roasted ginger warms the middle and dispels cold, dries dampness and eliminates phlegm, and coptis and scutellaria clear away heat and dry dampness as the auxiliary medicine; roasted ginger assists pinellia with its pungent dispersing effect, and coptis and scutellaria assist pinellia with its bitterness descending effect, and the three ingredients balance cold and heat, pungent dispersing effect and bitterness descending effect, lift and lower the qi mechanism, eliminate abdominal distension and promote circulation; and codonopsis and jujube are used as auxiliary ingredients to assist the spleen and stomach in transportation and transformation, costus root, amomum villosum, and salvia miltiorrhiza in promoting qi, removing blood stasis, and relieving pain; charred hawthorn, stir-fried barley sprout, and stir-fried malt in eliminating accumulation and stagnation, invigorating the spleen and stomach, harmonizing the stomach and stopping diarrhea, and cuttlefish bone in reducing acidity, relieving pain and stopping bleeding; the whole formula has the functions of dispersing stagnation and eliminating abdominal distension, invigorating the stomach and digesting food, eliminating accumulation and stagnation, and promoting qi and relieving pain.

[0036] Comparative advantages in efficacy: The time for relieving gastric bloating of this traditional Chinese medicine preparation is shortened to 1.8 days (traditional Banxia Xiexin Decoction requires 3.2 days), the HP eradication rate is increased to 78.1% (traditional Banxia Xiexin Decoction is 55%), the gastric mucosal repair cycle is shortened to 4.2 weeks (traditional Banxia Xiexin Decoction is 6.5 weeks), and the recurrence rate within one year is reduced to 12.3% (traditional Banxia Xiexin Decoction is 34.7%).

[0037] This embodiment provides a traditional Chinese medicine preparation for treating chronic gastropathy. Targeted at the complex pathogenesis of modern spleen and stomach diseases, the traditional Banxia Xiexin Decoction is modified. While maintaining the core principle of Banxia Xiexin Decoction in regulating both cold and heat, the preparation innovates the compatibility of medicinal pairs to form a multi-target therapeutic system of "clearing heat and dampness - promoting qi and eliminating stagnation - reducing acid and protecting the membranes - activating blood circulation and unblocking meridians." The preparation is particularly suitable for the complex syndromes of modern chronic gastrointestinal diseases characterized by a mixture of cold and heat, mixed deficiency and excess, and accompanied by qi stagnation, blood stasis, and indigestion. The preparation also brings about a synergistic effect, which is mainly reflected in the following aspects:

[0038] First, it enhances its targeted effect. The addition of costus root and amomum villosum strengthens its efficacy in promoting qi and alleviating pain, invigorating the spleen and eliminating dampness, and improving the original formula's targeted effect on symptoms of qi stagnation, such as abdominal distension, belching, and acid reflux. Clinical observations have shown that the combination of costus root and amomum villosum can enhance gastrointestinal motility and relieve abdominal distension. The addition of charred hawthorn, stir-fried rice sprouts, and stir-fried malt (three sprouts) enhances digestion and stagnation, making it particularly effective for treating food stagnation and damp-heat syndromes caused by modern dietary irregularities, consistent with the pathogenesis of "damp-heat food stagnation" in the literature. The addition of cuttlefish bone neutralizes gastric acid and protects the mucosa, demonstrating its specific therapeutic effect on acid reflux, heartburn, and peptic ulcers. Clinically, its acid-reducing effect is comparable to that of Western medicine, with fewer side effects.

[0039] Second, the efficacy is optimized; wine-processed Scutellaria baicalensis and Coptis chinensis reduce their bitter and cold properties that damage the stomach while retaining their effects of clearing heat and drying dampness; roasted ginger has a milder warming property than dried ginger, making the pungent and bitter effects more moderate, making it suitable for patients with spleen and stomach deficiency and coldness; Salvia miltiorrhiza can promote blood circulation and remove blood stasis, and can improve symptoms such as epigastric stabbing pain and purple tongue in patients with gastric meridian stasis, forming a compatibility feature with Coptis chinensis and Scutellaria baicalensis that "clears heat without hindering blood circulation, and removes blood stasis without adding to heat."

[0040] Third, the indications are expanded; in view of the complex pathogenesis of chronic gastritis with erosion, gastric ulcer and other diseases with both cold and heat and internal blood stasis, this prescription uses cuttlefish bone to suppress acid and salvia miltiorrhiza to resolve blood stasis to form a treatment plan for both the symptoms and the root cause; the combination of costus root + amomum villosum + jiao sanxian can synergistically enhance gastrointestinal motility, and has an improvement effect on functional dyspepsia, gastroparesis and other diseases, and pays more attention to the restoration of the "descent" function than the original prescription.

[0041] Example 2

[0042] The preparation method for treating chronic gastropathy adopted in Example 1 can increase the content of active ingredients in the preparation, reduce the dosage of the drug, and reduce the carrying volume. In addition, the preparation process is reasonable, the production is simple, the cost is economical, and the stability is good, providing guidance for further development of the preparation.

[0043] The following is verified through specific experiments.

[0044] This experiment used the orthogonal experimental method to investigate the effects of factors such as the amount of water added to the medicinal materials, decoction time, and decoction times on the extraction amount of baicalin, the main active ingredient in Scutellaria baicalensis. The final relative density, viscosity, and clarity of the mixture were used as the molding indicators of the dosage form to screen the optimal extraction and molding processes of the mixture, providing a reference for basic research, preparation pilot research, and clinical application of the mixture.

[0045] 1. Experimental Materials

[0046] 1.1 Instruments

[0047] A decoction machine (Zhengzhou Jimi Machinery Equipment Co., Ltd., JMDJ-13L), an electronic balance (Shanghai Minqiao Precision Scientific Instrument Co., Ltd., FA1004), a rotary evaporator (Shanghai Leigu Instrument Co., Ltd., 3000 mL), a circulating cooler (Zhengzhou Great Wall Science and Technology Industry and Trade Co., Ltd., DL-400), a rotary evaporator (Tokyo Physical and Chemical Instruments Co., Ltd., N-1300), a pH meter (Shanghai Youke Instrument Co., Ltd., PHS-3E), a high performance liquid chromatograph (Shimadzu Corporation, Japan), and a chromatographic column (Shimadzu Corporation, Japan).

[0048] 1.2 Drug testing

[0049] The medicinal materials including French pinellia, dried ginger, wine-soaked scutellaria, wine-soaked coptis, Codonopsis pilosula, costus root, Amomum villosum, Salvia miltiorrhiza, cuttlefish bone, charred hawthorn, fried rice sprouts, fried malt, roasted licorice, and jujube were purchased from Chongqing Tongjun Pavilion Co., Ltd. All medicinal materials were identified before use and complied with the relevant provisions under each medicinal material item of the 2020 edition of the "Chinese Pharmacopoeia".

[0050] Baicalin (National Institutes for Food and Drug Control, 110715-202223), glycyrrhetinic acid (Münster, A0038), 6-gingerol (Dest, DJ0027-0020), berberine hydrochloride (source leaf, A10048), codonopsis pilosula (Münster, A0002), ursolic acid (Solebol, 77-52-1), Scutellaria baicalensis reference material (source leaf, B24228), Coptis chinensis reference material (source leaf, B24226), Codonopsis pilosula reference material (source leaf, B24248), Salvia miltiorrhiza reference material (source leaf, B24248); the methanol used for content determination was chromatographically pure, and all other reagents were of analytical grade.

[0051] 2. Experimental methods

[0052] 2.1. Study on the extraction process of mixture

[0053] 2.1.1 Determination of water absorption rate of medicinal slices

[0054] Weigh three portions of the herbs in the recipe described in Example 1, proportionately, and soak each in 8-fold the amount of water. Check the soaking status every 30 minutes until the herbs are completely soaked. Filter out any unabsorbed water, weigh it, and calculate the average water absorption rate of the recipe using the following formula.

[0055] Water absorption rate = (wet weight of medicinal material - dry weight of medicinal material) / dry weight of medicinal material × 100%

[0056] 2.1.2 Orthogonal Experimental Design

[0057] According to the prescription ratio, we weighed the following medicinal materials: Pinellia ternata, dried ginger, wine-smelling scutellaria, wine-smelling coptis root, Codonopsis pilosula, costus root, Amomum villosum, Salvia miltiorrhiza, cuttlefish bone, charred hawthorn, stir-fried rice sprouts, stir-fried malt, roasted liquorice root, and jujube. Design L9(3 4 ) Orthogonal experiment. A: Amount of water added (times), B: Decoction time (min), C: Number of extractions (times) were the main factors to be investigated, and baicalin extraction yield and dry paste yield were used as evaluation indicators. The design of each factor level is shown in Table 1.

[0058] Table 1. Levels of factors in orthogonal experiment of decoction conditions

[0059]

[0060] 2.1.3 Extraction method

[0061] Weigh 201g of medicinal slices according to the prescription ratio and randomly divide them into 9 parts under parallel operation conditions. 4 ) combination mode was tested, the decoction was passed through a 200-mesh sieve, the filtrates were combined and concentrated to 700 mL for the determination of baicalin extraction amount and dry paste yield.

[0062] 2.1.4 Determination of baicalin content

[0063] 2.1.4.1 Chromatographic conditions

[0064] The content determination method under "Scutellaria baicalensis" in the 2020 edition of the Chinese Pharmacopoeia was used, with a Shimadzu C18 (250 mm × 4.6 mm, 5 μm) column; methanol-water-phosphoric acid (47:53:0.2) as the mobile phase; the detection wavelength was 280 nm; the column temperature was 30 °C; the injection volume was 10 μL; and the flow rate was 1.0 mL min -1 .

[0065] 2.1.4.2 Preparation of reference solution

[0066] Take an appropriate amount of baicalin reference substance dried under reduced pressure at 60°C for 4 hours, accurately weigh it, and add methanol to make a solution containing 80 μg per 1 mL.

[0067] 2.1.4.3 Preparation of negative control solution

[0068] Prepare a mixture without wine-infused scutellaria baicalensis according to the prescription ratio and the same process. Accurately measure 1 mL of the mixture without wine-infused scutellaria baicalensis, place it in a 50 mL volumetric flask, add methanol to the scale, shake well, filter with a microporous filter membrane, and take the filtrate to obtain the mixture.

[0069] 2.1.4.4 Preparation of test solution

[0070] Accurately measure 1 mL of the mixture, place it in a 50 mL volumetric flask, add methanol to the mark, shake well, filter with a microporous membrane, and obtain the filtrate.

[0071] 2.1.5 Thin layer chromatography

[0072] 2.1.5.1、French Pinellia

[0073] (1) Preparation of test solution

[0074] Take 50 mL of this product, evaporate to dryness in a water bath, add 40 mL of ethanol, soak in cold for about 10 minutes, heat under reflux for 1 hour, filter, evaporate the filtrate to dryness, add ethanol, and make up to 5 mL as the test solution.

[0075] (2) Preparation of reference solution

[0076] Take the glycyrrhetinic acid reference substance and add anhydrous ethanol to make a solution containing 1 mg per 1 mL as the reference solution.

[0077] (3) Thin layer chromatography identification

[0078] Pipette 2 μL of reference solution and 5 μL of test solution, spot them respectively on the same silica gel GF254 thin layer plate, use petroleum ether (30-60℃)-ethyl acetate-acetone-formic acid (30:6:5:0.5) as the developing agent, develop, take out, dry, and inspect under ultraviolet light at 254 nm.

[0079] 2.1.5.2 Dried ginger

[0080] (1) Preparation of test solution

[0081] Take 30 mL of this product, evaporate to dryness in a water bath, add 20 mL of ethyl acetate, ultrasonically treat for 10 min, filter, and take the filtrate as the test solution.

[0082] (2) Preparation of sample solution

[0083] Take 6-gingerol reference substance and add ethyl acetate to make a solution containing 0.5 mg per 1 mL as the reference solution.

[0084] (3) Thin layer chromatography identification

[0085] Pipette 10 μL of each of the above solutions and spot them on the same silica gel G thin layer plate. Use cyclohexane-ether (1:1) as the developing agent, develop, take out, dry, spray with 10% sulfuric acid ethanol solution, heat at 105℃ until clear color appears, and examine under ultraviolet light at 365nm.

[0086] 2.1.5.3. Scutellaria baicalensis with wine

[0087] (1) Preparation of test solution

[0088] Take 50 mL of this product, evaporate to dryness in a water bath, add 20 mL of ethanol, filter, evaporate the filtrate to dryness, add 1 mL of methanol to dissolve the residue, and use it as the test solution.

[0089] (2) Preparation of control medicinal material solution

[0090] Take 1 g of Scutellaria baicalensis reference medicinal material, add 30 mL of a mixed solution of ethyl acetate and methanol (3:1), heat and reflux for 30 min, cool, filter, evaporate the filtrate to dryness, add 5 mL of methanol to dissolve the residue, and take the supernatant to prepare a reference medicinal material solution in the same way.

[0091] (3) Preparation of reference solution

[0092] Take berberine hydrochloride reference substance and add methanol to make a solution containing 0.5 mg per 1 mL, which is used as the reference substance solution.

[0093] (4) Thin layer chromatography identification

[0094] 1 μL of each of the above solutions was taken and spotted on the same silica gel G thin layer plate, and developed with n-butanol-water-glacial acetic acid (7:2:1). The plate was taken out, dried, and examined under a UV lamp at 365 nm.

[0095] 2.1.5.4. Coptis chinensis with wine

[0096] (1) Preparation of test solution

[0097] Take 30 mL of this product, evaporate to dryness in a water bath, add 25 mL of methanol, ultrasonically treat for 30 min, filter, and take the filtrate as the test solution.

[0098] (2) Preparation of control medicinal material solution

[0099] Take 0.25 g of Rhizoma Coptidis as a control medicinal material and prepare a control medicinal material solution in the same manner.

[0100] (3) Preparation of reference solution

[0101] Take berberine hydrochloride reference substance and add methanol to make a solution containing 0.5 mg per 1 mL, which is used as the reference substance solution.

[0102] (4) Thin layer chromatography identification

[0103] 1 μL of each of the above solutions was taken and spotted on the same silica gel G thin layer plate, and developed with n-butanol-water-glacial acetic acid (7:2:1). The plate was taken out, dried, and examined under a UV lamp at 365 nm.

[0104] 2.2. Research on the molding process of compound preparations

[0105] 2.2.1. Dosage form selection

[0106] In accordance with the relevant regulations such as "Registration Management of Traditional Chinese Medicine Preparations Prepared by Medical Institutions Using Traditional Techniques", and combined with the clinical application of this drug, the existing traditional technology is used to prepare the mixture.

[0107] 2.2.2 Investigation of Concentration Process

[0108] The extracts were concentrated to 250, 200, and 150 mL, respectively, and the baicalin concentration, total amount, retention rate, relative density, and viscosity in the concentrates were tested.

[0109] 2.2.3. Investigation of pH value

[0110] The pH value of the medicinal material stock solution is about 5.62 (25°C). Take 5 samples, 30 mL each, and adjust the pH of the extract to 4.5, 5.0, 5.5, 6.0, and 6.5 with hydrochloric acid or sodium hydroxide, which are pharmaceutical excipients included in the 2020 edition of the Pharmacopoeia. Let it stand and place it in a constant temperature and humidity stability test box. Control the temperature at 25±2°C and RH at 60%±5%. Observe the clarity of the solution after 1 day, 3 days, and 10 days.

[0111] 2.2.4. Selection of flavoring agents

[0112] Add an appropriate amount of stevioside to 5 parts of the original medicinal material solution, stir to dissolve it, observe the state of the solution, and taste its taste.

[0113] 2.2.5. Investigation of preservatives

[0114] The mixture is a liquid preparation. The preservatives that can be selected for liquid preparations mainly include benzoic acid, sorbic acid, parabens, etc., and the selection of preservatives is determined according to the pH value of the liquid.

[0115] 3. Experimental results

[0116] 3.1. Optimization of mixture preparation process

[0117] 3.1.1 Determination of water absorption rate of medicinal slices

[0118] The optimal soaking time was chosen when the weight of the medicinal material no longer increased significantly. The best soaking time was chosen to be 70 minutes before decocting the Chinese medicine. The results of the water absorption rate of the slices are shown in Table 2.

[0119] Table 2 Water absorption results of decoction pieces

[0120]

[0121]

[0122] 3.1.2 Orthogonal Experiment Results

[0123] A variance analysis of the results for baicalin extraction and dry paste yield revealed that the order of influence on dry paste yield and baicalin content among the three factors was C > A > B. Factor C, i.e., the number of decoctions, had a significant effect on dry paste yield and baicalin content, while factors A and B, i.e., the amount of water added and the decoction time, had no significant effect on dry paste yield. Because the length of decoction time had little impact, and to save factory costs, the optimal process was selected as adding 8 times the amount of water, decoction for 30 minutes, and decoction three times. Therefore, the preferred process was A3B1C3. Specific results are shown in Tables 3 and 4.

[0124] Table 3L9(3 4 ) Orthogonal experimental design and results of water extraction process

[0125]

[0126]

[0127] Table 4 Analysis of variance

[0128]

[0129] 3.1.3 Verification test

[0130] The verification results are shown in Table 5. The average extraction amount of baicalin by water decoction was 1.43 g, and the average yield of dry paste was 26.77. The verification results were basically consistent with the orthogonal test, proving that this process was stable and feasible.

[0131] Table 5 Orthogonal test verification results

[0132]

[0133] 3.1.4 Results of the Methodological Investigation of Baicalin Content Determination

[0134] 3.1.4.1 Specificity test

[0135] The chromatograms of baicalin reference solution, mixture test solution and negative control solution were measured respectively, such as Figures 1 to 3 As shown, the mixture test sample has a chromatographic peak at the corresponding retention time of the baicalin reference substance, while the negative control has no peak at the corresponding retention time, indicating that other components in the prescription have no interference with the determination of baicalin.

[0136] 3.1.4.2. Draw the standard curve

[0137] The above-mentioned reference solution was accurately diluted to prepare 6 different concentrations of reference solution: 5, 10, 20, 40, 60, and 80 μg / mL. The solution was determined according to the above-mentioned chromatographic conditions. The standard curve was drawn with the concentration of baicalin as the abscissa (X) and the peak area as the ordinate (Y). The linear equation was: Y = 24521X - 15351, R 2 =0.9993, indicating that baicalin has a good linear relationship in the range of 5-80 μg / mL.

[0138] Table 6 Linear relationship investigation results

[0139]

[0140] 3.1.4.3 Precision test

[0141] Accurately pipette 10 μL of the baicalin reference solution and inject it six times in succession. Record the peak area and calculate the RSD to be 1.14%. The results are shown in Table 7, indicating good instrument precision.

[0142] Table 7 Precision inspection results

[0143]

[0144] 3.1.4.4 Repeatability Study

[0145] Prepare six test solutions of this product using the method described in "2.1.4." Determine the peak area of baicalin under the above chromatographic conditions. The calculated RSD is 1.82%. See Table 8 for the results.

[0146] Table 8 Repeatability test

[0147]

[0148] 3.1.4.5 Stability Investigation

[0149] Prepare the test solution using the method described in "2.1.4" using the drug solution. Under the above chromatographic conditions, the solution was measured at 0, 4, 6, 8, 20, and 24 hours. The calculated RSD was 0.5%, indicating that the test solution was stable within 24 hours. The results are shown in Table 9.

[0150] Table 9 Stability Study

[0151]

[0152] 3.1.4.6. Sample recovery test

[0153] Accurately measure 1 mL of a mixture with a known baicalin content and place it in a 50 mL volumetric flask. Six replicates were added to each of the 6 aliquots, with 1 mL of a 1.7 mg / mL baicalin reference solution added. Add methanol to the mark and shake well. Then, take 1 mL and place it in a 5 mL volumetric flask. Add methanol to the mark and shake well. Filter through a microporous membrane. Determine the peak area according to the chromatographic conditions described above, and calculate the recovery. The results are shown in Table 10.

[0154]

[0155] Table 10 Sample recovery

[0156]

[0157] 3.1.5 Thin layer chromatography test results

[0158] The thin layer chromatography identification chart of Pinellia ternata, dried ginger, wine-processed Scutellaria baicalensis and wine-processed Coptis chinensis in the extract is shown in the figure below. Figure 5 (In the picture, A: Pinellia ternata, B: Dried ginger, C: Scutellaria baicalensis with wine, D: Coptis chinensis with wine).

[0159] 3.2. Forming process of compound preparation

[0160] 3.2.1. Investigation of Concentration Process

[0161] Taking into account various factors such as production cost and active ingredient content, 200 mL was selected as the optimal concentration condition. At this time, the relative density of the mixture was measured to be 1.10 (Table 11).

[0162] Table 11 Results of the concentration process investigation

[0163]

[0164]

[0165] 3.2.2. pH value investigation

[0166] If the pH value of a Chinese medicine liquid preparation is too high or too low, the solubility of some ingredients in it will be reduced or the sol state will be destroyed, resulting in precipitation. For example, alkaloids, saponins, amino acids, etc. will cause turbidity, precipitation, discoloration, or bubble formation due to changes in pH. An appropriate pH value can improve the clarity of the preparation and the stability of the medicinal liquid. Therefore, in order to ensure the quality of the preparation, the pH value is investigated in this embodiment. The results are shown in Table 12. The medicinal liquid is relatively stable in the pH range of 4.5 to 6.0. When it is higher than 6.0, more precipitation will appear after being left for a long time. Considering that the optimal pH value for human body absorption and utilization of the drug is 4.0 to 9.0, the pH value of the extract of this product is controlled at 4.5 to 6.0. When it exceeds 6.0, 0.1 mol / L hydrochloric acid is used to adjust it to this range to maintain the stability of the medicinal liquid system.

[0167] Table 12 pH value investigation results

[0168]

[0169] 3.2.3 Selection of flavoring agents

[0170] We selected steviol glycoside as the flavoring agent for this mixture. Steviol glycoside is a glycoside extracted from the leaves of plants in the Asteraceae family and is characterized by high sweetness and low caloric energy. While minimizing the amount of flavoring agent added, we examined the pH value, mouthfeel, and clarity of the solution after adding the flavoring agent, evaluating its effect on the smell and taste of the solution. The results are shown in Table 13: The experiment showed that the mouthfeel was significantly improved when 0.2g of steviol glycoside was added, so the dosage of steviol glycoside was determined to be 0.3g / 200mL.

[0171] Table 13 Selection of flavoring agents

[0172]

[0173] 3.2.4 Selection of preservatives

[0174] Without preservatives, the pH of the original solution is approximately 5.62. The optimal pH range for benzoic acid and its salts is 2.5 to 4.0; above pH 5.0, the antibacterial effect is suboptimal. Paraben preservatives are poorly soluble in water and are not suitable for this preparation. Potassium sorbate is an acidic preservative that is readily soluble in water, but its preservative effect decreases with increasing pH, so it is best used below pH 6.0. The typical dosage of sorbic acid as a preservative is 0.15% to 0.2%. To ensure antibacterial efficacy, this preparation uses 0.2% potassium sorbate.

[0175] 4. Discussion and Summary

[0176] At present, the content of precious and fine medicinal materials or the main medicine in the prescription is generally tested in the detection of Chinese patent medicines and traditional Chinese medicine preparations. However, there is no content detection item for Pinellia ternata in the pharmacopoeia, and there is no content detection item for dried ginger in the pharmacopoeia. The dosage of Coptis chinensis is relatively small. Modern research shows that baicalin in Scutellaria baicalensis has pharmacological activities such as anti-inflammatory and antioxidant effects. Baicalin can alleviate gastric mucosal damage caused by chronic atrophic gastritis, promote gastric mucosal cell proliferation, inhibit gastric mucosal cell apoptosis, and ultimately play a role in repairing gastric mucosa. Therefore, in this preparation study, baicalin in Scutellaria baicalensis was used as the main investigation indicator for preparation process and content determination.

[0177] The active ingredients in traditional Chinese medicine compound preparations are diverse and complex, and the appropriate extraction process will directly affect the active ingredient content and clinical efficacy of the preparation. This experiment selected three factors: the amount of water added, the number of extractions, and the decoction time. The orthogonal test method was used to investigate the water extraction process conditions. Ultimately, considering factors such as production efficiency, cost, and actual production operations, the optimal extraction process for the mixture was determined to be adding 8 times the amount of water, decoct for 30 minutes, and extract three times. In addition, this embodiment also investigated the molding process and ultimately determined that the final volume of the preparation was 200mL, the pH was controlled at 4.5-6.0, the amount of steviol glycosides was 0.3g, and the preservative was selected as 0.2% potassium sorbate. In summary, this experiment studied the effects of the water extraction process, the type of excipients, and the amount of excipients added on the active ingredient content, preparation form, and taste of the preparation, and obtained the optimal preparation process, providing a preliminary process for the future mass production of the mixture.

[0178] Finally, it should be noted that this article uses specific examples to illustrate the principles and implementation methods of the present invention. The description of the above embodiments is only used to help understand the core idea of the present invention. Without departing from the principles of the present invention, the present invention can also be improved and modified in several ways, and these improvements and modifications also fall within the scope of protection of the present invention.

Claims

1. A Chinese medicine preparation for treating chronic gastropathy, characterized in that: The Chinese medicine preparation is prepared from the following raw materials in parts by weight: 7-11 parts of French Pinellia, 7-11 parts of dried ginger, 8-12 parts of wine-soaked Scutellaria, 4-6 parts of wine-soaked Coptis, 13-17 parts of Codonopsis, 4-8 parts of costus root, 1-8 parts of Amomum villosum, 13-17 parts of Salvia miltiorrhiza, 8-12 parts of cuttlefish bone, 10-14 parts of charred hawthorn, 13-17 parts of stir-fried rice sprouts, 13-17 parts of stir-fried malt, 4-8 parts of roasted liquorice, and 8-12 parts of jujube.

2. A Chinese medicine preparation for treating chronic gastropathy according to claim 1, characterized in that: The Chinese medicine preparation is prepared from the following raw materials in parts by weight: 9 parts of French Pinellia, 9 parts of dried ginger, 10 parts of wine-soaked Scutellaria, 5 parts of wine-soaked Rhizoma Coptidis, 15 parts of Codonopsis pilosula, 6 parts of costus root, 6 parts of Amomum villosum, 15 parts of Salvia miltiorrhiza, 10 parts of cuttlefish bone, 12 parts of charred hawthorn, 15 parts of stir-fried rice sprouts, 15 parts of stir-fried malt, 6 parts of roasted liquorice root and 10 parts of jujube.

3. A method for preparing a traditional Chinese medicine preparation for treating chronic gastropathy, characterized in that: The following steps are involved: The raw materials are weighed and mixed according to the mass fractions as claimed in claim 1 or 2, soaked in water, decocted, and filtered to obtain an extract, which is combined with excipients to be processed into a specific dosage form.

4. The method for preparing a traditional Chinese medicine preparation for treating chronic gastropathy according to claim 3, wherein: The amount of water used is 6 to 10 times the total weight of the raw material.

5. The method for preparing a traditional Chinese medicine preparation for treating chronic gastropathy according to claim 4, wherein: The amount of water used is 8 times the total weight of the raw material.

6. The method for preparing a traditional Chinese medicine preparation for treating chronic gastropathy according to claim 3, wherein: The soaking time is 70 to 100 minutes, and the decoction time is 30 to 60 minutes.

7. The method for preparing a traditional Chinese medicine preparation for treating chronic gastropathy according to claim 6, characterized in that: The decoction time is 30 minutes.

8. The method for preparing a traditional Chinese medicine preparation for treating chronic gastropathy according to claim 3, characterized in that: The decoction is performed 3 times.

9. The method for preparing a traditional Chinese medicine preparation for treating chronic gastropathy according to claim 3, characterized in that: The auxiliary materials include steviol glycoside as steviol glycoside and / or potassium sorbate as a preservative. The dosage of steviol glycoside is 0.3g / 200mL, and the dosage of potassium sorbate is 0.2%.

10. The method for preparing a traditional Chinese medicine preparation for treating chronic gastropathy according to claim 3, characterized in that: The preparation is an oral preparation with a volume of 200 mL and a pH controlled at 4.5 to 6.0.

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