Improved coronary heart storax pill preparation method

Abstract

The invention discloses an improved coronary heart storax pill preparation method, and belongs to the technical field of coronary heart storax pill preparation. The preparation method comprises the following steps: crushing sandalwood, crushing elecampane, crushing frankincense, treating borneol and pelleting, the crushing of frankincense comprises the following two processes: dry crushing and wet crushing, and different pelleting methods are adopted according to different crushing methods of frankincense. According to the invention, a cryogenic grinding or low-temperature wet grinding process is adopted, so that the problem that frankincense cannot be ground by a conventional method is solved; according to the invention, low-temperature closed grinding is adopted, so that volatilization and oxidation loss of thermosensitive component medicines in sandalwood and elecampane are avoided; according to the process, the borneol is dissolved in the storax by adopting ethanol solubilization and then mixed with the medicinal powder to prepare the pill, so that the problems that the borneol is difficult to crush, is easy to lose due to thermal volatilization in the crushing process and is not uniformly distributed in the pill in the traditional process are solved.

Description

Technical Field

[0001] The present invention belongs to the technical field of the preparation of Guanxin Suhe Pills, and particularly relates to an improved preparation method of Guanxin Suhe Pills. Background Art

[0002] Guanxin Suhe Pills are composed of five traditional Chinese medicines, namely styrax, borneol, frankincense, sandalwood, and alpine immortelle root. The Chinese Pharmacopoeia records its prescription composition as: "styrax 50g, frankincense (processed) 105g, alpine immortelle root 210g, borneol 105g, sandalwood 210g"; its functions and indications are "having the effects of regulating qi, relieving fullness in the chest, and relieving pain. It is used for chest impediment caused by cold congealing and qi stagnation, and blockage of the heart meridian, manifested as chest tightness and precordial pain; for patients with coronary heart disease angina pectoris presenting with the above syndromes." Clinically, Guanxin Suhe Pills are not only used to treat coronary heart disease angina pectoris, but also widely used in various departments such as dermatology, pediatrics, and digestion, such as psoriasis, acute abdominal pain, and gastric ulcer. In addition, there are reports on the treatment of allergic rhinitis, biliary ascariasis, penile retraction, vertex pain, food poisoning coma, pediatric asthma, heat stroke, bilateral eye twitching, stomachache, dysmenorrhea, etc. with Guanxin Suhe Pills.

[0003] Guanxin Suhe Pills have the effects of reducing arterial blood pressure, dilating coronary arteries and peripheral blood vessels, increasing coronary blood flow, reducing coronary resistance and total peripheral resistance; improving left ventricular work and reducing myocardial oxygen utilization rate. Guanxin Suhe Pills significantly inhibit the apoptosis of myocardial cells in rats with acute myocardial infarction models and down-regulate the protein expression of Bax gene. Each dose group of Guanxin Suhe can significantly increase the survival rate of damaged myocardial cells, and there is an obvious dose correlation. This result indicates that the serum containing Guanxin Suhe has an obvious protective effect on peroxidative damage of myocardial cells. Long-term administration can dilate coronary arteries, improve myocardial ischemia, protect the heart vascular endothelium, promote angiogenesis, establish collateral circulation, enhance cardiovascular function, increase exercise tolerance, improve the quality of life, and reduce and prevent the recurrence rate of angina pectoris and myocardial infarction.

[0004] The formula concept of Guanxin Suhe Pills is "aromatic resuscitation", which is the traditional Chinese medicine pharmacological mechanism for treating acute attacks of coronary heart disease. It is generally taken by buccal or chewing, with rapid onset, and is particularly suitable for patients with initial angina pectoris. When such patients initially use nitrate drugs, they often experience side effects such as headache, head distension, and dizziness, while Guanxin Suhe Pills have no such side effects, and their compliance is better than that of nitrate drugs. Therefore, it is often used as a drug for treating acute attacks of coronary heart disease.

[0005] Guanxin Suhe Pills have the function of aromatic resuscitation. The volatile components of the Chinese medicinal materials in the prescription are important pharmacodynamic substances. Therefore, ensuring that the volatile components of the drug are not lost during the preparation process is crucial for the efficacy of Guanxin Suhe Pills. The preparation process of Guanxin Suhe Pills specified in the Chinese Pharmacopoeia is as follows: "Of the above five flavors, except Styrax and Borneol, the other three flavors, namely Olibanum (processed), etc., are pulverized into fine powder and sifted. Borneol is ground fine, mixed with the above powder by trituration, sifted, and mixed evenly; separately, an appropriate amount of refined honey is taken, warmed slightly, added to Styrax, stirred evenly, and then mixed with the above powder to make 1000 pills; or Borneol is ground fine, mixed evenly with a part of the fine powder of Olibanum (processed), etc., to make pill cores, and the remaining fine powder is used to coat the pill cores with Styrax and an appropriate amount of refined honey to make 1000 pills, thus obtaining the product." Production practice shows that due to the characteristics of the two medicinal materials, Olibanum and Borneol, in actual production, it is impossible to pulverize them into fine powder with various existing pulverizing equipment and pulverizing methods, which not only affects the uniformity of the preparation but also affects the extraction of active ingredients. Moreover, Borneol will volatilize and be lost during pulverization, resulting in a decrease in content and affecting the therapeutic effect; in addition, conventional pulverizing methods often cause the loss of aromatic components in the medicinal materials of Santalum album L. and Inula helenium L. Therefore, it is necessary to improve the original preparation process to solve the problems existing in the traditional process and ensure the drug quality of Guanxin Suhe Pills. Summary of the Invention

[0006] In view of the above situation, to overcome the defects of the prior art, the present invention improves the original preparation process to solve the problems existing in the traditional process and ensure the drug quality of Guanxin Suhe Pills.

[0007] To achieve the above object, the following technical solutions are adopted: The present invention provides an improved preparation method of Guanxin Suhe Pills, comprising the following steps:

[0008] S1. Pulverization of Santalum album L.: Santalum album L. is broken, and a low-temperature oscillating mill is used to grind it at a temperature below -5°C for 60 - 120 minutes to obtain a powder that can pass through a 200-mesh sieve;

[0009] S2. Pulverization of Inula helenium L.: Inula helenium L. is coarsely crushed, and a freezing oscillating mill is used to grind it at a temperature below -5°C for 60 - 120 minutes to obtain a powder that can pass through a 200-mesh sieve;

[0010] S3. Pulverization of Olibanum: The pulverization of Olibanum includes the following two processes:

[0011] S301. Dry pulverization: Olibanum is frozen at a temperature below -16°C for 10 hours, and then pulverized into coarse powder with a conventional pulverizer; the coarse powder is frozen again at a temperature below -16°C for 14 hours, taken out and pulverized into extremely fine powder with a conventional pulverizer, and the powder is stored frozen for later use;

[0012] S302, Wet grinding: Place frankincense in a low-temperature oscillating grinder, add purified water twice the weight of frankincense, and grind at -10°C for 60 - 90 minutes to form a suspension that can all pass through a 250-mesh sieve;

[0013] S4, Treatment of borneol: Take the prescribed amount of borneol and dissolve it in 1 times the amount of 95% ethanol to make a borneol ethanol solution;

[0014] S5, Pill making: According to the different crushing processes of frankincense, the pill making includes the following two processes:

[0015] S501, When frankincense is crushed by dry method, the pill making process includes:

[0016] Weigh the prescribed amount of sandalwood powder, costus root powder, and frankincense powder, and mix them evenly;

[0017] Take the prescribed amount of storax, slowly add the borneol ethanol solution while stirring, and stir evenly to make a storax borneol solution;

[0018] Take the refined honey, heat it to 40 - 50°C, then add the storax borneol solution, stir well, and then mix it evenly with the above powder to make pills;

[0019] S502, When frankincense is crushed by wet method, the pill making method includes:

[0020] Weigh the prescribed amount of sandalwood powder and costus root powder, and mix them evenly;

[0021] Take the prescribed amount of storax, slowly add the borneol ethanol solution while stirring, and stir evenly to make a storax borneol solution;

[0022] Take the refined honey, add it to the frankincense suspension, heat and concentrate it over medium heat, cool it to 40 - 50°C, add the storax borneol solution, stir well, and then mix it evenly with the above powder to make pills.

[0023] Furthermore, the Guanxin Suhe Pills contain: 50 g of storax, 105 g of frankincense, 210 g of costus root, 105 g of borneol, and 210 g of sandalwood.

[0024] Furthermore, the mesh number of the superfine powder in step S301 is 200 - 400 meshes.

[0025] Furthermore, the particle size of frankincense in the suspension in step S302 is ≤50 μm.

[0026] Furthermore, the refined honey in step S501 is 0.5 - 0.8 times the weight of the sandalwood powder, costus root powder, and frankincense powder.

[0027] Furthermore, the refined honey in step S502 is 0.5 - 0.8 times the weight of the sandalwood powder and costus root powder.

[0028] The beneficial effects of the present invention are as follows:

[0029] (1) The present invention adopts a cryogenic grinding or low-temperature wet grinding process, which solves the problem that frankincense cannot be ground by conventional methods.

[0030] (2) The present invention adopts low-temperature sealed grinding, which avoids the volatilization and oxidation loss of heat-sensitive components in sandalwood and costus root.

[0031] (3) In this process, borneol is dissolved in storax by ethanol solubilization and then mixed with the medicinal powder to make pills, which solves the problems that borneol is difficult to grind in the traditional process, is easily lost due to heat volatilization during grinding, and is unevenly distributed in the pills. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 FIG. is a flow chart of an improved method for preparing Guanxin Suhe Pills of the present invention.

[0033] The drawings are used to provide a further understanding of the present invention, and constitute a part of the specification. Together with the embodiments of the present invention, they are used to explain the present invention, and do not constitute a limitation to the present invention. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0034] The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0035] Unless otherwise defined, all professional and scientific terms used herein have the same meaning as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to the described content can be applied to the present invention. The preferred methods and materials described herein are only for illustrative purposes and do not limit the content of this application.

[0036] The experimental methods in the following embodiments are all conventional methods unless otherwise specified. The test materials used in the following embodiments are all obtained from commercial channels unless otherwise specified.

[0037] Example 1

[0038] An improved method for preparing Guanxin Suhe Pills includes the following steps:

[0039] S1. Crushing of sandalwood: The sandalwood is broken and ground by a low-temperature oscillating grinder at a temperature below -5°C for 60 - 120 minutes into a powder that can pass through a 200-mesh sieve.

[0040] S2. Crushing of Inula Root: Coarsely crush the Inula root and use a cryogenic oscillating mill to grind it at a temperature below -5°C for 60 - 120 minutes until it is crushed into a powder that can pass through a 200-mesh sieve.

[0041] S3. Crushing of Frankincense: Dry crushing: Place frankincense in a freezer at a temperature below -16°C for 10 hours and powder it into coarse powder using a conventional crusher; place the coarse powder in the freezer again at a temperature below -16°C for 14 hours, take it out and powder it into extremely fine powder with a particle size of 200 - 400 meshes using a conventional crusher, and store the powder frozen for later use.

[0042] S5. Pill making: Weigh the prescribed amounts of sandalwood powder, Inula root powder, and frankincense powder and mix them evenly; take the prescribed amount of storax, slowly add the borneol ethanol solution while stirring, and stir evenly to make the storax borneol solution; add the refined honey, which is 0.5 - 0.8 times the weight of the sandalwood powder, Inula root powder, and frankincense powder, heated to 40 - 50°C, to the storax borneol solution, stir well, and then mix it evenly with the above-mentioned powder to make pills.

[0043] The said Guanxin Suhe Pills contain: 50 g of storax, 105 g of frankincense, 210 g of Inula root, 105 g of borneol, and 210 g of sandalwood.

[0044] Example 2

[0045] An improved method for preparing Guanxin Suhe Pills, comprising the following steps:

[0046] S1. Crushing of Sandalwood: Crush the sandalwood and use a cryogenic oscillating mill to grind it at a temperature below -5°C for 60 - 120 minutes until it is crushed into a powder that can pass through a 200-mesh sieve.

[0047] S2. Crushing of Inula Root: Coarsely crush the Inula root and use a cryogenic oscillating mill to grind it at a temperature below -5°C for 60 - 120 minutes until it is crushed into a powder that can pass through a 200-mesh sieve.

[0048] S3. Crushing of Frankincense: Wet crushing: Place frankincense in a cryogenic oscillating mill, add purified water twice the weight of frankincense, and grind it at -10°C for 60 - 90 minutes until it is ground into a suspension that can all pass through a 250-mesh sieve, where the particle size of frankincense particles ≤ 50 μm.

[0049] S4. Treatment of Borneol: Take the prescribed amount of borneol and dissolve it in 95% ethanol in an amount of 1 times the weight to make a borneol ethanol solution.

[0050] S5. Pill Making: Weigh the prescribed amounts of sandalwood powder and costus root powder, mix them evenly; take the prescribed amount of storax, slowly add the borneol ethanol solution while stirring, and stir well to make the storax borneol solution; add the refined honey, which is 0.5 - 0.8 times the weight of the sandalwood powder and costus root powder, to the frankincense suspension, heat and concentrate it over medium heat, cool it to 40 - 50 °C, add the storax borneol solution, stir well, and then mix it evenly with the above-mentioned powder to make pills.

[0051] The said Guanxin Suhe Pills contain: 50 g of storax, 105 g of frankincense, 210 g of costus root, 105 g of borneol, and 210 g of sandalwood.

[0052] Result Analysis

[0053] Test Example 1

[0054] Retention of volatile oil in the fine sandalwood powder prepared by different comminution processes

[0055] Compare the retention of volatile oil in the fine sandalwood powder prepared by different comminution processes:

[0056] 1.1 Method for determining volatile oil: Weigh 30 g of the sample precisely, and determine the content of volatile oil according to the "Method A for Determination of Volatile Oil" in "General Rules 2204" of the Chinese Pharmacopoeia (Volume IV, 2020 Edition).

[0057] 1.2 Preparation of fine sandalwood powder:

[0058] Slice and coarsely crush the sandalwood medicinal material, and then prepare different fine sandalwood powders according to the following operations respectively;

[0059] 1.2.1 Fine sandalwood powder prepared by conventional comminution process (CTXF): Coarsely crushed sandalwood is crushed into fine powder of 120 meshes with a conventional pulverizer;

[0060] 1.2.2 New process fine sandalwood powder: Use a low-temperature oscillating grinder to grind the coarsely crushed sandalwood at a temperature below -5 °C for 90 minutes, and crush it into powder that can pass through a 120-mesh sieve; then use a 200-mesh sieve to separate the fine powder NTXF200 that can pass through a 200-mesh sieve and the fine powder NTXF120 that cannot pass through a 200-mesh sieve.

[0061] 1.3 Test and determination results

[0062] Prepare 5 samples of fine sandalwood powder by each of the three processes, respectively take samples and determine the content of volatile oil in them according to the above method. The determination results are as follows in the table:

[0063] The content of volatile oil in the coarsely crushed sandalwood is 3.22%.

[0064] Table 1 Test results of volatile oil content of three samples

[0065]

[0066] As can be seen from the experimental results in Table 1, when preparing sandalwood fine powder by conventional pulverizer, the temperature of sandalwood rises significantly during the pulverization process, resulting in a greater loss of volatile oil, which drops from the original 3.22% to 1.69%. By using low-temperature cryogenic grinding and pulverization, because the whole process is at low temperature and isolated from air, the volatile components in sandalwood are effectively retained. The volatile oil content in NTXF200 fine powder is slightly higher than that in NTXF120 fine powder and sandalwood coarse particles, indicating that the finer the pulverization fineness of sandalwood, the more conducive to the extraction of volatile oil. The experimental results show that using the new process (low-temperature oscillating grinding) to pulverize sandalwood can ensure no loss of volatile oil and more sufficient extraction of volatile oil compared with the traditional pulverization method.

[0067] Test Example 2

[0068] Comparison of borneol content in pills of traditional process and new process

[0069] Compare the borneol content in the Guanxin Suhe Pills prepared by the traditional process and the Guanxin Suhe Pills prepared by the new process. The Guanxin Suhe Pills CGX were prepared by the traditional process (i.e., the process recorded in the pharmacopoeia), and the Guanxin Suhe Pills NGX were prepared by this process (frankincense was pulverized by wet method). Five batches were prepared for each.

[0070] 2.1 Borneol detection method (gas chromatography)

[0071] 2.1.1 Chromatographic conditions and system suitability test: Using polyethylene glycol 20000 (PEG-20M) as the stationary phase, the coating concentration is 10%; the column temperature is 140 °C. The number of theoretical plates calculated based on the n-pentadecane peak should not be less than 1200.

[0072] 2.2.2 Determination of correction factor: Take an appropriate amount of n-pentadecane, accurately weigh it, and prepare a solution containing 7 mg per 1 ml with ethyl acetate as the internal standard solution. Take another 10 mg of borneol reference substance, accurately weigh it, place it in a 5 ml volumetric flask, accurately add 1 ml of the internal standard solution, add ethyl acetate to the scale, shake well, take 1 μl and inject it into the gas chromatograph for determination, and calculate the correction factor.

[0073] 2.2.3 Determination method: Take 10 pills of this product, accurately weigh and grind them evenly; accurately add an equal amount of diatomaceous earth and grind evenly. Take an appropriate amount (about equivalent to 12 mg of borneol), accurately weigh it, place it in a stoppered test tube, accurately add 1 ml of the internal standard solution and 4 ml of ethyl acetate, stopper tightly, shake well to dissolve the borneol, and let it stand. Take 1 μl of the supernatant and inject it into the gas chromatograph for determination. Calculate based on the sum of the peak areas of borneol and isoborneol.

[0074] 2.2 Detection results

[0075] 2.2.1 The borneol content in Guanxin Suhe Pills of different batches is shown in Table 2.

[0076] Table 2 Borneol Content in Guanxin Suhe Pills of Different Batches

[0077] Batch number of CGX pills Borneol content (mg / pill) Batch number of NGX pills Borneol content (mg / pill) 20240501 75.6 20240601 101.0 20240502 80.1 20240602 97.8 20240503 86.7 20240603 96.5 20240504 92.3 20240604 98.3 20240505 90.8 20240605 97.9

[0078] From the test results of the borneol content in the pills of the two processes, it can be seen that the borneol content in the traditional-process Guanxin Suhe Pills is lower than that in the new-process pills; among different batches of the traditional-process Guanxin Suhe Pills, the borneol content fluctuates greatly, while the borneol content among different batches of the new-process Guanxin Suhe Pills is relatively close. The reason for this situation is related to the volatile and adhesive properties of borneol. Borneol is a crystalline drug, extremely volatile and sublimable. The heat generated by shearing and impact during comminution can easily cause its volatilization, and it adheres into pieces on the surface of the equipment and cannot be further comminuted; when compounded with other medicinal powders, the heat generated further causes volatilization loss, resulting in a low borneol content in the final pills, and even the situation of not meeting the drug standard (80.0 - 120.0 mg / pill). Using the new process to process borneol avoids the volatilization loss of borneol, and directly dissolves borneol in styrax (oil) by ethanol solubilization. Therefore, the borneol content in each batch of pills is relatively stable and close.

[0079] 2.2.2 The distribution of borneol in the pills of the same batch of Guanxin Suhe Pills is shown in Table 3.

[0080] Randomly take 10 samples from the same batch of Guanxin Suhe Pills, with two pills in each sample, and operate according to the determination method to detect the borneol content of each sample.

[0081] Table 3 Distribution of Borneol in the Pills of the Same Batch of Guanxin Suhe Pills

[0082]

[0083] The test results in Table 3 show that the borneol content in the new-process pills is basically the same, while the borneol in the traditional-process pills is unevenly distributed and the content difference is large, which also conforms to our prediction of the traditional process. Because borneol is extremely easy to adhere into pieces due to the heat generated by grinding and the force, resulting in being unable to be further comminuted into fine powder, and also making it difficult to be fully mixed with other medicinal powders during the subsequent mixing, so the situation of uneven distribution of borneol in the pills of the same batch occurs. The new process dissolves borneol in the styrax alcohol solution and then mixes it with the medicinal powder to make pills, ensuring the uniform distribution of borneol in each pill.

[0084] Although the embodiments of the present invention have been shown and described, for those of ordinary skill in the art, it can be understood that various changes, modifications, substitutions, and variations can be made to these embodiments without departing from the principles and spirit of the present invention. The scope of the present invention is defined by the appended claims and their equivalents.

[0085] The above describes the present invention and its implementation manners. Such description is not restrictive. What is shown in the drawings is only one of the implementation manners of the present invention, and the actual application is not limited thereto. In summary, if those of ordinary skill in the art are inspired by it and, without departing from the gist of the present invention, design in a non-creative manner similar ways and embodiments to the technical solution, they shall fall within the protection scope of the present invention.

Claims

1. An improved method for preparing Guanxin Suhe Pills, characterized in that: The following steps are involved: S1. Crushing sandalwood: crush the sandalwood and grind it at a temperature below -5°C using a low-temperature oscillating grinder to form a powder that can pass through a 200-mesh sieve; S2. Grinding of Inula officinalis: Grinding the Inula officinalis coarsely, using a frozen oscillating grinder, at a temperature below -5°C, into a powder that can pass through a 200-mesh sieve; S3, crushing of frankincense: the crushing of frankincense includes the following two processes: S301, dry grinding: freezing the frankincense at a temperature below -16°C for 10 hours, and grinding it into coarse powder using a conventional grinder; freezing the coarse powder again at a temperature below -16°C for 14 hours, taking it out and grinding it into very fine powder using a conventional grinder, and freezing the powder for later use; S302, wet grinding: placing the frankincense in a low-temperature oscillating grinder, adding purified water twice the weight of the frankincense, grinding at -10°C to form a suspension that can completely pass through a 250-mesh sieve; S4. Processing of borneol: Take the prescribed amount of borneol and dissolve it in 1 times the amount of 95% ethanol to prepare a borneol ethanol solution; S5, pill making: According to different processes of crushing frankincense, the pill making includes the following two processes: S501. When frankincense is crushed by dry method, the process of making pills includes: Weigh the prescribed amount of sandalwood powder, incense powder, and frankincense powder and mix them evenly; Take the amount of styrax, slowly add the borneol ethanol solution, add while stirring, stir evenly, to make a styrax borneol solution; Heat the refined honey to 40-50°C, add the storax borneol solution, stir evenly, and then mix with the above powder to make pills; S502: When frankincense is pulverized by wet method, the pilling method includes: Weigh the prescribed amount of sandalwood powder and incense powder and mix them evenly; Take the amount of styrax, slowly add the borneol ethanol solution, add while stirring, stir evenly, to make a styrax borneol solution; Take refined honey and add it to frankincense suspension, heat over medium heat to concentrate, cool to 40-50℃, add storax and borneol solution, stir well, then mix with the above powder and make pills.

2. The improved method for preparing Guanxin Suhe Pills according to claim 1, characterized in that: The Guanxin Suhe Pills contain: 50g of storax, 105g of frankincense, 210g of inula, 105g of borneol, and 210g of sandalwood.

3. The improved method for preparing Guanxin Suhe Pills according to claim 2, characterized in that: The mesh size of the ultrafine powder in step S301 is 200-400 meshes.

4. The improved method for preparing Guanxin Suhe Pills according to claim 3, characterized in that: The particle size of the frankincense particles in the suspension in step S302 is ≤50 μm.

5. The improved method for preparing Guanxin Suhe Pills according to claim 4, characterized in that: In step S501, the refined honey is 0.5-0.8 times the weight of the sandalwood powder, inulin powder and frankincense powder.

6. The improved method for preparing Guanxin Suhe Pills according to claim 5, characterized in that: In step S502, the refined honey is 0.5-0.8 times the weight of the sandalwood powder and the incense powder.

7. The improved method for preparing Guanxin Suhe Pills according to claim 6, characterized in that: The grinding time of step S1 is 60-120 minutes.

8. The improved method for preparing Guanxin Suhe Pills according to claim 7, characterized in that: The grinding time of step S2 is 60-120 minutes.

9. The improved method for preparing Guanxin Suhe Pills according to claim 8, characterized in that: The grinding time of step S302 is 60-90 minutes.

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