A preparation method for increasing stability of suhe xiang pills

Abstract

This invention belongs to the field of pharmaceutical preparation and provides a method for increasing the stability of Suhexiang pills: The active ingredients, such as resins and volatile oils, are extracted from frankincense and benzoin using ethanol, and then dissolved with borneol and artificial musk along with the styrax in the prescription. This invention improves the stability of Suhexiang pills and extends their shelf life by changing the preparation process without altering the formulation. Furthermore, the addition of excipients increases the dissolution rate of fat-soluble active ingredients in the prescription, improving its efficacy and eliminating long-standing problems associated with Suhexiang pill formulations, thus enhancing the stability and efficacy of the formulation. This process is simple, low-cost, and suitable for industrial production.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical preparation and relates to an improvement on the preparation method of Suhexiang pills. Background Technology

[0002] The information disclosed in this background section is intended to enhance understanding of the overall background of the invention and is not necessarily to be construed as an admission or in any way implying that such information constitutes prior art known to those skilled in the art.

[0003] Solid Chinese medicine preparations containing small molecules such as borneol and menthol, which have sublimation properties, often precipitate on the surface of the preparation during storage due to the migration or sublimation of these small molecules. This forms a layer of borneol (menthol) "frost" crystals or snowflake-like borneol (menthol) crystals, resulting in substandard "properties" of the preparation. If the storage time is longer, the borneol will evaporate and be lost, affecting the efficacy of the preparation.

[0004] Musk has the effects of opening the orifices and waking the mind, promoting blood circulation and regulating menstruation, reducing swelling and relieving pain. It is often used to treat critical illnesses such as delirium due to fever, stroke with phlegm syncope, and sudden syncope due to qi stagnation. The main active ingredient in musk is muscone (which is also the main aroma component of musk). Muscone is insoluble in water and highly volatile. How to prevent the volatilization of muscone in musk has always been a difficult problem to solve. For example, musk is often stored together with angelica and made into solid preparations (such as pills) by coating them with gold to extend the shelf life of the preparations. However, from the perspective of modern pharmaceutical requirements, neither of these methods is suitable. Therefore, how to prevent the volatilization loss of muscone in solid Chinese medicine preparations containing musk and ensure the efficacy of the preparations is an urgent problem to be solved.

[0005] Suhe Pill is a medicine listed in the Chinese Pharmacopoeia. It has the functions of aromatic resuscitation, qi regulation, and pain relief, and is a commonly used medicine in clinical practice for treating hemiplegia caused by stroke. The prescription for Suhe Pill in the Pharmacopoeia is as follows: 50g of styrax, 100g of benzoin, 50g of borneol, 200g of concentrated buffalo horn powder, 75g of artificial musk, 100g of sandalwood, 100g of agarwood, 100g of cloves, 100g of cyperus rotundus, 100g of costus root, 100g of prepared frankincense, 100g of long pepper, 100g of atractylodes macrocephala, 100g of chebula pulp, and 100g of cinnabar. The preparation method is as follows: Except for styrax, artificial musk, borneol, and concentrated buffalo horn powder, cinnabar is water-milled into a very fine powder; the remaining ten ingredients, including benzoin, are pulverized into a fine powder; the artificial musk, borneol, and concentrated buffalo horn powder are separately ground into fine powder, then mixed with the above powders, sieved, and thoroughly combined. The styrax is then simmered until dissolved, and then mixed with an appropriate amount of refined honey and water to make 960 water-honey pills, which are then dried at low temperature; or, an appropriate amount of refined honey is added to make 960 large honey pills. Its functions and indications are aromatic opening of the orifices, promoting qi circulation and relieving pain. It is used for phlegm-induced syncope and coma, stroke-induced hemiplegia, limb weakness, as well as heatstroke and stomach and heart pain caused by phlegm obstructing the heart orifices. The clinical dosage is relatively large. However, the styrax pills prepared according to the method specified in the pharmacopoeia have two major drawbacks during storage: firstly, borneol in the prescription can migrate to the surface of the pills, forming white spots like snowflakes, which does not meet the requirements of the preparation quality standards, and borneol is also easily lost through volatilization, affecting the efficacy; secondly, muscone in the artificial musk in the prescription is easily lost through volatilization, which can significantly affect the efficacy of the styrax pills. Summary of the Invention

[0006] To address the issue of unstable quality caused by the precipitation of borneol and the volatilization of musk active ingredients in Suhexiang pills, this invention provides a preparation method to improve the stability of Suhexiang pills. By changing the preparation process and adding appropriate excipients, the above problems are prevented, thereby improving the stability of Suhexiang pills, extending their storage time, and increasing the solubility of fat-soluble active ingredients in the prescription through the addition of excipients, thus enhancing their efficacy.

[0007] To achieve the above objectives, the present invention adopts the following technical solution.

[0008] A method for preparing styrax pills with increased stability includes the following steps: (1) Take frankincense and benzoin, add ethanol and reflux to extract, filter, and obtain frankincense and benzoin ethanol extract; (2) Add borneol to the ethanol extract of frankincense and benzoin to dissolve it, and recover the ethanol until there is no ethanol smell, to obtain a mixture of frankincense, benzoin and borneol; (3) Add artificial musk to styrax and stir well to obtain a mixture of artificial musk and styrax; (4) Heat and melt the mixture of frankincense, benzoin and borneol, add the mixture of artificial musk and styrax, stir well, then add the fine powder of sandalwood, agarwood, clove, cyperus, costus root, long pepper, atractylodes macrocephala, chebula pulp, very fine cinnabar powder, concentrated buffalo horn powder and an appropriate amount of refined honey, mix well and make styrax pills.

[0009] Preferably, in step (1), the concentration of ethanol is not less than 95%, and the amount of ethanol used is 4-6 times the total mass of frankincense and benzoin. The extraction method is reflux extraction. To expedite the extraction process, frankincense and benzoin can be appropriately crushed before extraction. Preferably, the extraction time is 1-3 hours.

[0010] Preferably, in step (2), the recovery of ethanol until there is no ethanol odor refers to the recovery of ethanol at atmospheric pressure and at a temperature not exceeding 80°C.

[0011] Preferably, in step (3), the styrax is in a softened state. For example, the styrax is heated to below 60°C, such as 40-50°C.

[0012] Preferably, the melting temperature is 70-80℃. First, add the mixture of artificial musk and styrax and stir for 10-30 minutes until well mixed. Then, add fine powder of cinnabar, sandalwood and other medicinal powders, and an appropriate amount of refined honey, mix well, and make styrax pills.

[0013] The styrax pills are made from the following raw materials: 50 parts by weight of styrax, 100 parts by weight of benzoin, 50 parts by weight of borneol, 200 parts by weight of concentrated buffalo horn powder, 75 parts by weight of artificial musk, 100 parts by weight of sandalwood, 100 parts by weight of agarwood, 100 parts by weight of cloves, 100 parts by weight of cyperus rotundus, 100 parts by weight of costus root, 100 parts by weight of frankincense (processed), 100 parts by weight of long pepper, 100 parts by weight of atractylodes macrocephala, 100 parts by weight of chebula pulp, and 100 parts by weight of cinnabar.

[0014] A styrax pill obtained by the above preparation method.

[0015] The present invention has the following advantages: This invention uses ethanol to extract active ingredients such as resins and volatile oils from frankincense and benzoin. This not only removes ineffective components such as gums from frankincense and benzoin, but also utilizes the lipid solubility of resins to dissolve borneol and artificial musk together with styrax in the formula, preventing borneol migration and muscone volatilization. This invention eliminates long-standing problems in styrax pill formulations by modifying the preparation process without changing the formulation itself, thus enhancing the stability and efficacy of the formulation. The process is simple, low-cost, and suitable for industrial production. Detailed Implementation

[0016] This invention provides a method for preparing styrax pills with enhanced stability, comprising the following steps: (1) Take frankincense and benzoin, crush them slightly, add 4-6 times the mass of ethanol with a concentration of not less than 95wt%, heat and reflux for 1-3 hours, filter, and obtain ethanol extract; (2) Add borneol to the ethanol extract of frankincense and benzoin to dissolve it. Recover the ethanol at normal pressure under a temperature not exceeding 80°C until there is no ethanol odor, and obtain a mixture of frankincense, benzoin and borneol. (3) Heat the styrax to 40-50℃, add artificial musk, stir for 10-30 minutes until well mixed, and obtain a mixture of styrax and artificial musk; (4) Heat the mixture of frankincense, benzoin and borneol to 70-80℃ to melt it, add the mixture of styrax and artificial musk, stir for 10-30 minutes until well mixed, then add cinnabar powder and other fine powders such as sandalwood and an appropriate amount of refined honey, mix well, and make styrax pills.

[0017] The present invention will be further described below with reference to specific embodiments. Unless otherwise specified, the prescription quantities are those in the "Suhexiang Pills" prescription in the 2020 edition of the Chinese Pharmacopoeia, that is, to prepare 960 Suhexiang pills, the following ingredients are required: 50g of styrax, 100g of benzoin, 50g of borneol, 200g of concentrated buffalo horn powder, 75g of artificial musk, 100g of sandalwood, 100g of agarwood, 100g of cloves, 100g of cyperus rotundus, 100g of costus root, 100g of frankincense (processed), 100g of long pepper, 100g of atractylodes macrocephala, 100g of chebula pulp, and 100g of cinnabar, to make 960 pills.

[0018] Example 1 Optimization of the preparation method 1. Optimization of extraction conditions for frankincense and benzoin The concentration of extracted ethanol, the amount of extracted ethanol used, and the extraction time were investigated using orthogonal experiments. The factors and levels investigated are shown in Table 1.

[0019] Table 1 Factors and levels investigated in frankincense extraction Take frankincense and benzoin separately and crush them appropriately. Weigh 10.00g of frankincense fragments and crush them according to the factor levels in Table 1 and L9(3). 4 The orthogonal experimental combination was subjected to reflux extraction. The extract was filtered, and the residue was stored separately. The filtrate was diluted to 100 mL with the appropriate amount of ethanol and shaken well. 20 mL of each extract was accurately pipetteed into an evaporating dish that had been dried to constant weight. After evaporating to dryness in a water bath, the mixture was dried at 105 °C for 3 hours, cooled in a desiccator for 30 minutes, and then quickly and accurately weighed to calculate the amount of extract. The results are shown in Table 2.

[0020] Table 2. Results of orthogonal experiments on the extraction of frankincense and benzoin. The experimental results show that the concentration of ethanol has the greatest impact on the extraction results. When the ethanol concentration exceeds 95%, the results are less different. Therefore, the concentration of ethanol used for extraction should be ≥95%. Secondly, the amount of extraction solvent is important. The results of level 2 and level 3 are closer, so the amount of extraction solvent should be 4-6 times the concentration. The extraction time has the least impact on the extraction results; there is no significant difference among the three levels, so the extraction time should be 1-3 hours.

[0021] 2. Determination of the melting temperature of a mixture of frankincense, benzoin, and borneol. The mixture of frankincense, benzoin, and borneol is solid at room temperature, but has a low melting point. It can be melted at low temperature and then mixed with a mixture of styrax and musk.

[0022] Therefore, the melting range of the mixture of frankincense, benzoin, and borneol was determined to identify the control conditions during preparation. The melting range of the frankincense, benzoin, and borneol mixture was determined according to Method II of Melting Point Determination in General Chapter 0612 of the 2020 edition of the Chinese Pharmacopoeia. The results showed that the mixture of frankincense, benzoin, and borneol began to "initially melt" at 70.6℃ and completely melted at 79.8℃, i.e., "finally melted." Therefore, the temperature for melting the mixture of frankincense, benzoin, and borneol was determined to be controlled between 70-80℃.

[0023] Example 2: Preparation of Styrax Pills (1) Take the prescribed amount of frankincense and benzoin, crush them slightly, add 4 times the mass of 95wt% ethanol, heat and reflux for 3 hours, filter, and obtain ethanol extract; (2) Add borneol to the ethanol extract obtained in step (1) to dissolve it, and recover the ethanol under normal pressure at a temperature not exceeding 80°C until there is no ethanol odor, to obtain a mixture of frankincense, benzoin and borneol; (3) Heat the styrax to 45°C, add artificial musk, stir for 30 minutes to mix well, and obtain a mixture of styrax and artificial musk; (4) Heat the mixture of frankincense, benzoin and borneol to a molten state at 75°C, add the mixture of styrax and artificial musk, stir for 30 minutes until well mixed, then add other medicinal ingredients and appropriate amounts of refined honey and water, mix well, and make styrax pills (honey pills).

[0024] Example 3: Preparation of Styrax Pills (1) Take the prescribed amount of frankincense and benzoin, crush them slightly, add 6 times the mass of 95wt% ethanol, heat and reflux for 2 hours, filter, and obtain ethanol extract; (2) Add borneol to the ethanol extract obtained in step (1) to dissolve it, and recover the ethanol under normal pressure at a temperature not exceeding 80°C until there is no ethanol odor, to obtain a mixture of frankincense, benzoin and borneol; (3) Heat the styrax to 48°C, add artificial musk, stir for 20 minutes to mix well, and obtain a mixture of styrax and artificial musk; (4) Heat the mixture of frankincense, benzoin and borneol to a molten state at 78°C, add the mixture of styrax and artificial musk, stir for 30 minutes until well mixed, then add other medicinal ingredients and appropriate amounts of refined honey and water, mix well, and make styrax pills (honey pills).

[0025] Example 4: Preparation of Styrax Pills (1) Take the prescribed amount of frankincense and benzoin, crush them slightly, add 6 times the mass of anhydrous ethanol, heat and reflux for 1 hour, filter, and obtain ethanol extract; (2) Add borneol to the ethanol extract obtained in step (1) to dissolve it, and recover the ethanol under normal pressure at a temperature not exceeding 80°C until there is no ethanol odor, to obtain a mixture of frankincense, benzoin and borneol; (3) Heat the styrax to 45°C, add artificial musk, stir for 10 minutes to mix well, and obtain a mixture of styrax and artificial musk; (4) Heat the mixture of frankincense, benzoin and borneol to a molten state at 80°C, add the mixture of styrax and artificial musk, stir for 30 minutes until well mixed, then add other medicinal ingredients and appropriate amounts of refined honey and water, mix well, and make styrax pills (honey pills).

[0026] Comparative Example 1: Preparation of Styrax Pills Take the various Chinese herbs for Suhexiang Pills and prepare Suhexiang Pills (water-honey pills) according to the method under Suhexiang Pills in Part I of the 2020 edition of the Chinese Pharmacopoeia: Except for styrax, artificial musk, borneol, and concentrated buffalo horn powder, cinnabar is water-milled into an extremely fine powder; the remaining ten herbs, including benzoin, are pulverized into fine powder; artificial musk, borneol, and concentrated buffalo horn powder are separately ground into fine powder, mixed with the above powders, sieved, and thoroughly mixed. Then, styrax is stewed until dissolved, and an appropriate amount of refined honey and water are added to make 960 water-honey pills, which are then dried at low temperature.

[0027] Example 3: Stability of different Styrax pills The long-term stability of the styrax pills prepared in Examples 2, 3, 4 and the comparative example was observed.

[0028] 1. Visual Inspection Indicators The time it takes for borneol crystals to appear on the surface of Suhexiang pills reflects their appearance stability; the crystallization on the surface of the pills was observed at different times. 2. Borneol content The content of borneol in the pills was determined at different times. The method for determining the content of borneol was the same as that for determining the content of borneol in Compound Niuhuang Qingwei Pills in the 2020 edition of the Chinese Pharmacopoeia. The amount of borneol and isoborneol was also determined. 3. Musk ketone content The content of muscone in the pills was determined at different times. The method for determining the content of muscone was the same as the method for determining the content of artificial musk in Xiaojin Pills in the 2020 edition of the Chinese Pharmacopoeia.

[0029] Table 3. Stability and active ingredient content of different styrax pills As shown in Table 3, the stability of Suhexiang pills prepared using the improved process is significantly better than that prepared using the pharmacopoeia process. It can prevent the precipitation of borneol and significantly reduce the volatilization loss of borneol and musk. The preparation process provided by this invention improves the quality and efficacy of traditional Chinese medicine preparations without changing the original formula. This process is simple and suitable for large-scale factory production.

[0030] The above description is merely an embodiment of this application and is not intended to limit the scope of this application. Various modifications and variations can be made to this application by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the scope of the claims of this application.

Claims

1. A method for preparing styrax pills with increased stability, characterized in that, Includes the following steps: (1) Take frankincense and benzoin, add ethanol and reflux to extract, filter, and obtain frankincense and benzoin ethanol extract; (2) Add borneol to the ethanol extract of frankincense and benzoin to dissolve it, and recover the ethanol until there is no ethanol smell, to obtain a mixture of frankincense, benzoin and borneol; (3) Add artificial musk to styrax and stir well to obtain a mixture of artificial musk and styrax; (4) Heat and melt the mixture of frankincense, benzoin and borneol, add the mixture of artificial musk and styrax, stir well, then add the fine powder of sandalwood, agarwood, clove, cyperus, costus root, long pepper, atractylodes macrocephala, chebula pulp, very fine cinnabar powder, concentrated buffalo horn powder and an appropriate amount of refined honey, mix well and make styrax pills.

2. The preparation method according to claim 1, characterized in that, In step (1), the concentration of ethanol is not less than 95%, and the amount of ethanol used is 4-6 times the total mass of frankincense and benzoin; The extraction method is heating and reflux extraction; frankincense and benzoin are appropriately crushed before extraction; preferably, the extraction time is 1-3 hours.

3. The preparation method according to claim 1, characterized in that, In step (2), the ethanol is recovered until there is no ethanol odor by using atmospheric pressure recovery and the temperature does not exceed 80°C.

4. The preparation method according to claim 1, characterized in that, In step (3), the melting temperature is 70-80℃; the state of styrax is softened.

5. The preparation method according to any one of claims 1-4, characterized in that, The styrax pills are made from the following raw materials: 50 parts by weight of styrax, 100 parts by weight of benzoin, 50 parts by weight of borneol, 200 parts by weight of concentrated buffalo horn powder, 75 parts by weight of artificial musk, 100 parts by weight of sandalwood, 100 parts by weight of agarwood, 100 parts by weight of cloves, 100 parts by weight of cyperus rotundus, 100 parts by weight of costus root, 100 parts by weight of frankincense (processed), 100 parts by weight of long pepper, 100 parts by weight of atractylodes macrocephala, 100 parts by weight of chebula pulp, and 100 parts by weight of cinnabar.

6. A styrax pill obtained by the preparation method according to any one of claims 1-5.

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