Guanxinshengmai pill and preparation method thereof

Abstract

This application relates to the field of traditional Chinese medicine preparations and discloses a Guanxin Shengmai Pill, comprising the following ingredients, by weight: 7-12 parts ginseng, 7-12 parts ophiopogon, 2-5 parts schisandra chinensis, 12-20 parts salvia miltiorrhiza, 10-15 parts red peony root, 7-12 parts curcuma, and 0.4-0.8 parts Panax notoginseng powder. The following excipients, based on the total weight of the medicinal materials, are also included: 0.2%-0.5% xanthan gum, 0.1%-0.3% chitosan, 1%-2% β-cyclodextrin, and 30%-50% refined honey. By employing a dual-phase extraction technique combining water-soluble and fat-soluble extraction, and by performing segmented extractions tailored to the characteristics of water-soluble components (such as ginsenosides and tanshinones) and fat-soluble components (such as schisandrin A and curcumin), the invention incorporates adsorption purification and molecular distillation techniques to achieve a 30%-40% increase in the extraction rate of key active ingredients while reducing impurity interference, addressing issues such as insufficient active ingredient content and unstable efficacy.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine preparations, in particular to a Guanxinshengmai pill and a preparation method thereof. Background Art

[0002] Cardiovascular disease is one of the leading causes of death and disability worldwide, with its incidence increasing year by year. Hyperlipidemia and coronary heart disease, in particular, have become major chronic diseases threatening human health. Traditional treatment options mainly include two methods:

[0003] Western medicine treatment: represented by statins, aspirin and other drugs, which work by lowering blood lipid levels, anti-thrombotic and improving vascular function.

[0004] Interventional procedures: including coronary artery stent implantation and bypass surgery, which restore blood vessel patency through mechanical means.

[0005] In recent years, Traditional Chinese Medicine (TCM) has received widespread attention as an adjunctive treatment for cardiovascular diseases due to its multi-target and low side effect profile, particularly in the long-term management of chronic diseases. However, the development and application of traditional TCM preparations still face numerous challenges. The extraction process for traditional TCM preparations primarily relies on water boiling, and single heating extraction can easily lead to inadequate release of ingredients. For example, key ingredients such as ginsenosides and tanshinones are released slowly at low temperatures, while high-temperature extraction can cause degradation of some active ingredients.

[0006] In the existing technology, the extraction of fat-soluble components (such as schisandrin A and tanshinone) is more difficult. A single water extraction process cannot achieve efficient extraction of both water-soluble and fat-soluble components, resulting in a low content of key active ingredients in the final product and insignificant efficacy.

[0007] Existing Chinese medicine extracts often contain a large amount of impurities (such as polysaccharides, proteins, etc.). These impurities not only reduce the concentration of the active ingredients in the medicine, but may also cause the preparation to be unstable and the efficacy to fluctuate greatly.

[0008] Some technologies attempt to increase the concentration of extracts through a single concentration method, but lack efficient purification technology (such as macroporous resins and molecular distillation), resulting in poor product quality consistency and difficulty in meeting the standards of modern Chinese medicine preparations. Summary of the Invention

[0009] In view of the deficiencies in the prior art, the present invention provides a Guanxin Shengmai Pill and a preparation method thereof, which solves the problems of low extraction efficiency, high impurity content, poor stability and low bioavailability in traditional Chinese medicine preparations.

[0010] To achieve the above objectives, the present invention is implemented through the following technical solutions: A Guanxin Shengmai Pill, comprising the following raw material components in parts by weight:

[0011] 7-12 parts of ginseng, 7-12 parts of ophiopogon, 2-5 parts of schisandra, 12-20 parts of salvia, 10-15 parts of red peony root, 7-12 parts of turmeric, 0.4-0.8 parts of notoginseng powder;

[0012] The following excipients are also included based on the total weight of the medicinal materials:

[0013] Xanthan gum 0.2%~0.5%, chitosan 0.1%~0.3%, β-cyclodextrin 1%~2%, refined honey 30%~50%.

[0014] A preparation method of Guanxinshengmai pills comprises the following steps:

[0015] Medicinal material pretreatment: Weigh ginseng, ophiopogon japonicus, schisandra chinensis, salvia miltiorrhiza, red peony root, turmeric and notoginseng powder according to the ratio. Except for notoginseng powder, wash, dry and grind the remaining medicinal materials into fine powder for later use;

[0016] Water-soluble extraction: Ginseng, Ophiopogon japonicus, Salvia miltiorrhiza and Paeonia lactiflora are subjected to water-soluble extraction, and after filtering to remove impurities, the water-soluble extract is concentrated to obtain a water-soluble extract;

[0017] Fat-soluble extraction: Perform fat-soluble extraction on Schisandra chinensis and Curcuma aromatica, recover the solvent and concentrate it to obtain a fat-soluble extract;

[0018] Mixed purification: The water-soluble extract is purified by an adsorption purification device, and the fat-soluble extract is removed from impurities by a separation device to obtain a high-purity extract;

[0019] Nano-inclusion: The extract is mixed with the inclusion material to form a stable inclusion compound;

[0020] Pill forming: Mix the extract with medicinal material powder and excipients, add forming materials, and prepare pills in a pill making device;

[0021] Drying and coating: The pills are dried and a protective film is coated on the surface of the pills to obtain the finished product.

[0022] Preferably, the water-soluble extract is filtered through a 200-mesh filter to remove large particle impurities, and is concentrated to a relative density of 1.20 to 1.25 using a vacuum concentration device.

[0023] Preferably, the extraction of Schisandra chinensis and Curcuma aromatica adopts a fat-soluble extraction method, adding 70% to 80% ethanol, and the microwave extraction conditions are power 600 to 800W, temperature 50 to 70°C, and time 10 to 20 minutes.

[0024] Preferably, the fat-soluble extract is subjected to a rotary evaporator to remove ethanol and is concentrated to a relative density of 1.15 to 1.20.

[0025] Preferably, the nano-inclusion process uses ultrasonic conditions with a power of 300 to 500 W for 15 to 25 minutes, and the inclusion ratio of water-soluble and fat-soluble extracts to β-cyclodextrin is 1:1.5 to 1:2.

[0026] Preferably, the proportion of refined honey added during pill molding is 35% to 45% of the total weight of the medicinal material powder, and the stirring time is 20 to 30 minutes.

[0027] Preferably, the temperature range of the drying process is 50-60° C., the time range is 8-12 hours, and the moisture content of the final pills is controlled at ≤8%.

[0028] Preferably, the concentration of the hydroxypropyl methylcellulose solution used in the coating process is 0.5% to 1%, the coating temperature is 40 to 50° C., and the coating is continued to dry for 2 to 4 hours.

[0029] Preferably, the extraction of ginseng, ophiopogon, salvia miltiorrhiza and red peony root adopts water-soluble extraction method, adding 8 to 12 times the weight of purified water, and performing ultrasonic-assisted extraction at 70 to 80° C., the ultrasonic power is 400 to 600 W, and the extraction time is 30 to 50 minutes.

[0030] The present invention provides a Guanxin Shengmai Pill and a preparation method thereof, which has the following beneficial effects:

[0031] 1. This invention utilizes a dual-phase extraction method that combines water-soluble and fat-soluble extraction. By performing segmented extraction based on the characteristics of water-soluble components (such as ginsenosides and tanshinones) and fat-soluble components (such as schisandrin and curcumin), and by incorporating adsorption purification and molecular distillation techniques, it achieves a 30%-40% increase in the extraction rate of key active ingredients while reducing impurity interference. Compared to the existing single extraction methods, which suffer from low extraction efficiency and high impurity content, this method addresses the issues of insufficient active ingredient content and unstable efficacy.

[0032] 2. The present invention utilizes a compounding technology of functional excipients, such as xanthan gum, chitosan, and β-cyclodextrin. The xanthan gum enhances the pill's molding strength and moisture resistance, while chitosan provides a sustained-release function. β-cyclodextrin enhances the stability and solubility of fat-soluble components through inclusion technology, achieving the technical effect of significantly improving drug stability and storage performance. Compared to existing technologies, where a single excipient results in fragile, moisture-absorbing, or deteriorating finished products, this solution addresses the problem of insufficient pill storage performance.

[0033] 3. The present invention combines segmented extraction with refined purification to achieve a significant improvement in the content of key active ingredients and product batch-to-batch consistency. Compared to existing techniques that often suffer from significant batch-to-batch variations in product quality due to numerous extraction impurities and significant process fluctuations, this approach addresses the inherent instability in product quality associated with traditional Chinese medicine preparation.

[0034] 4. This invention utilizes a design that combines nano-inclusion with chitosan sustained-release technology. Nano-inclusion enhances the solubility of fat-soluble ingredients, while chitosan provides sustained release, resulting in a two-fold increase in the bioavailability of the active ingredients. Compared to existing solutions that suffer from low absorption rates and poor utilization rates of insoluble ingredients in drugs, this solution addresses the issue of insufficient drug utilization in traditional Guanxin Shengmai Pills. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 It is a flow chart of the preparation method of the present invention. DETAILED DESCRIPTION

[0036] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0037] Please see the attached Figure 1 : Example

[0038] Example 1

[0039] Raw materials and formula

[0040] Main ingredients: Ginseng: 10g, Ophiopogon japonicus: 10g, Schisandra chinensis: 4g, Salvia miltiorrhiza: 18g, Paeonia lactiflora: 13g, Curcuma aromatica: 10g, Panax notoginseng powder: 0.6g

[0041] Excipients: Xanthan gum: 0.3% (based on the total weight of the medicinal material) Chitosan: 0.2% (based on the total weight of the medicinal material) β-cyclodextrin: 1.5% (based on the total weight of the medicinal material) Refined honey: 40% (based on the total weight of the medicinal material powder)

[0042] Preparation steps:

[0043] Medicinal Material Pretreatment: Wash ginseng, ophiopogon japonicus, schisandra chinensis, salvia miltiorrhiza, red peony root, and turmeric, dry at 50°C to a moisture content of ≤10%, and then grind to 80 mesh size for later use. Add Panax notoginseng powder according to the proportion and set aside.

[0044] For water-soluble extraction, place ginseng, Ophiopogon japonicus, Salvia miltiorrhiza, and Paeonia lactiflora in an extraction tank. Add 10 times the weight of the herbs in purified water. Perform ultrasonic-assisted extraction at 70°C, 500W power, for 40 minutes. Repeat two extractions. Combine the extracts, filter to remove large particles, and concentrate to a relative density of 1.22 (measured at 50°C).

[0045] For fat-soluble extraction, 8 times the weight of Schisandra chinensis and Curcuma aromatica was added to 75% ethanol and extracted at 700W microwave power and 60°C for 15 minutes. The extract was then concentrated to a relative density of 1.18 after recovering the ethanol using a rotary evaporator.

[0046] Mixed purification

[0047] The water-soluble extract was adsorbed by a macroporous resin and eluted with 30% ethanol. The eluate was collected and concentrated.

[0048] The fat-soluble extract is subjected to molecular distillation equipment to remove volatile impurities to obtain a high-purity extract.

[0049] Nanoinclusion The concentrated extract was mixed with β-cyclodextrin in a ratio of 1:1.5, and the ultrasonic power was set to 400 W for 20 minutes to form a nanoinclusion complex.

[0050] Pill Forming: The nano inclusion compound was evenly mixed with powder, xanthan gum and chitosan, 40% refined honey and appropriate amount of water were added, and pills with a diameter of about 4 mm were prepared by a pill making machine.

[0051] Drying and coating: Dry the pills at 55°C for 10 hours to a moisture content of ≤8%. Then coat with 0.8% hydroxypropyl methylcellulose solution at 45°C and continue drying for 3 hours.

[0052] Summary of Examples

[0053] This example significantly improved the extraction yield of key active ingredients (such as ginsenosides, tanshinone, and schisandrin A) by employing a dual-phase extraction and purification technique. Optimizing ultrasonic conditions during aqueous extraction significantly increased extraction efficiency by approximately 30%. Thanks to precise control of fat-soluble extraction, the extract purity was approximately 25% higher than traditional methods, significantly reducing impurities.

[0054] Example 2:

[0055] Raw materials and formula

[0056] Main ingredients: Ginseng: 9g, Ophiopogon japonicus: 8g, Schisandra chinensis: 3g, Salvia miltiorrhiza: 15g, Paeonia lactiflora: 12g, Curcuma aromatica: 9g, Panax notoginseng powder: 0.5g

[0057] Excipients: Xanthan gum: 0.4% (based on the total weight of the medicinal material), chitosan: 0.1% (based on the total weight of the medicinal material), β-cyclodextrin: 2% (based on the total weight of the medicinal material), refined honey: 45% (based on the total weight of the medicinal material powder)

[0058] Preparation steps:

[0059] Medicinal material pretreatment

[0060] After all the medicinal materials are cleaned, they are dried at 50℃ until the moisture content is ≤10%, and then crushed to 100 mesh for later use.

[0061] Water-soluble extraction

[0062] Ginseng, Ophiopogon japonicus, Salvia miltiorrhiza, and Paeonia lactiflora were added to purified water at a ratio of 10 times their weight. Ultrasonic extraction was performed at 75°C, 450W power, and 35 minutes. After filtration and removal of impurities, the extract was concentrated to a relative density of 1.20.

[0063] Fat-soluble extraction

[0064] The extracts of Schisandra chinensis and Curcuma aromatica were extracted with 70% ethanol at a microwave power of 650W, a temperature of 55°C, and a time of 12 minutes. The extract was concentrated to a relative density of 1.16.

[0065] Mixed purification

[0066] The water-soluble extract is adsorbed on a macroporous resin and eluted with 40% ethanol. The fat-soluble extract is passed through a molecular distillation device to remove impurities.

[0067] Nanoinclusion

[0068] The concentrated extract was mixed with β-cyclodextrin at a ratio of 1:2, and the ultrasonic power was set to 350 W for 25 minutes.

[0069] Pill forming

[0070] All extracts were mixed with medicinal material powder, xanthan gum, chitosan and refined honey to prepare water-honeyed pills with a diameter of 5 mm.

[0071] Drying and coating

[0072] After drying at 55°C for 12 hours, the film was coated with 1% hydroxypropyl methylcellulose solution at a coating temperature of 50°C and dried for 2 hours.

[0073] This example utilizes a xanthan gum and chitosan compounding process to enhance the formulation's moisture resistance and significantly improve its mechanical strength, addressing the fragility and moisture absorption issues of traditional pills. Furthermore, the inclusion of β-cyclodextrin further enhances the stability of the ingredients, demonstrating that the pills' shelf life is 30% longer than that of Example 1.

[0074] Example 3:

[0075] Raw materials and formula

[0076] Main ingredients: Ginseng: 8g, Ophiopogon japonicus: 7g, Schisandra chinensis (vinegar-fried): 4g, Salvia miltiorrhiza: 16g, Paeonia lactiflora: 14g, Curcuma aromatica: 11g, Panax notoginseng powder: 0.7g

[0077] Excipients: Xanthan gum: 0.2% (based on the total weight of the medicinal material), chitosan: 0.3% (based on the total weight of the medicinal material), β-cyclodextrin: 1% (based on the total weight of the medicinal material), refined honey: 35% (based on the total weight of the medicinal material powder)

[0078] Preparation steps

[0079] Medicinal material pretreatment

[0080] All medicinal materials were washed, dried to a moisture content of ≤10%, and crushed to 80 mesh.

[0081] Water-soluble extraction

[0082] Add 12 times the weight of the medicinal material with water, perform ultrasonic extraction at 70°C, power 500W, time 50 minutes, and concentrate to a relative density of 1.23.

[0083] Fat-soluble extraction

[0084] Schisandra chinensis and Curcuma aromatica were extracted with 75% ethanol at 8 times their weight, microwave power 750 W, temperature 65°C, time 18 minutes, and concentrated to a relative density of 1.17.

[0085] Mixed purification

[0086] The extract is purified and distilled to obtain high-purity components.

[0087] Nanoinclusion

[0088] The nanoinclusion ratio was set to 1:1.5, the ultrasonic power was 400 W, and the time was 20 min.

[0089] Pill forming

[0090] The nano inclusion compound is mixed with the powder, and refined honey and auxiliary materials are added to form pills with a diameter of 3 mm.

[0091] Drying and coating

[0092] Dry at 50℃ for 8 hours, apply 0.5% hydroxypropyl methylcellulose coating and dry for 3 hours.

[0093] Summary of Examples

[0094] This example combines chitosan with nano-inclusion technology to double the solubility of insoluble ingredients (such as schisandrin A), significantly enhancing their bioavailability. Compared to Examples 1 and 2, this example is more suitable for the long-term use needs of patients with chronic diseases.

[0095] Comparative Example

[0096] Comparative Example 1:

[0097] Preparation process:

[0098] Medicinal material pretreatment

[0099] Same as Example 1, all medicinal materials were washed, dried, and crushed to 80 mesh size for later use.

[0100] Water-soluble extraction

[0101] Place ginseng, ophiopogon japonicus, salvia miltiorrhiza, and red peony root in an extraction tank. Add 10 times the weight of the herbs in purified water. Heat the extract at 70°C without ultrasonic assistance. Extract once for 90 minutes. Filter to remove impurities, and concentrate to a relative density of 1.22.

[0102] Fat-soluble extraction

[0103] As in Example 1, Schisandra chinensis and Curcuma aromatica were extracted with 75% ethanol by microwave extraction at a power of 700 W, a temperature of 60° C., and a time of 15 minutes. The ethanol was recovered by rotary evaporation and concentrated to a relative density of 1.18.

[0104] Mixed purification

[0105] The water-soluble extract was directly mixed with the fat-soluble extract without being purified by macroporous resin.

[0106] Nanoinclusion

[0107] No nanoencapsulation was performed, and the extracts were directly mixed and used for pelleting.

[0108] Pill forming

[0109] The same method as in Example 1 was used, except that xanthan gum and chitosan were added, and 40% refined honey was added to prepare pills with a diameter of 4 mm.

[0110] Drying and coating

[0111] Same as Example 1, except that the drying conditions were 55° C., the time was 10 hours, and the coating process was the same.

[0112] Comparative Example 2:

[0113] Preparation process:

[0114] Medicinal material pretreatment

[0115] Same as Example 2, all medicinal materials were washed, dried, and crushed to 100 mesh for later use.

[0116] Water-soluble extraction

[0117] The same method as in Example 2 was used, but ultrasonic-assisted extraction was adopted at a power of 450 W for 35 minutes. After filtration, the product was concentrated to a relative density of 1.20.

[0118] Fat-soluble extraction

[0119] As in Example 2, Schisandra chinensis and Curcuma aromatica were extracted using 70% ethanol in a microwave oven at a microwave power of 650 W, a temperature of 55° C., and a time of 12 minutes.

[0120] Mixed purification

[0121] The water-soluble extract and the fat-soluble extract are directly mixed without using macroporous resin and molecular distillation equipment for purification.

[0122] Nanoinclusion

[0123] The ratio of β-cyclodextrin in the nano-inclusion process was reduced from 1:2 in Example 2 to 1:0.5, and sufficient inclusion was not achieved.

[0124] Pill forming

[0125] The addition amounts of xanthan gum and chitosan were adjusted to 0.1% and 0.05%, respectively, which were lower than the recommended ranges of Example 2. The ratio of refined honey was 50%.

[0126] Drying and coating

[0127] The mixture was dried at 50°C for 6 hours (shorter than the recommended drying time in the embodiment) using a 0.2% hydroxypropyl methylcellulose solution.

[0128] Comparative Example 3:

[0129] Preparation process:

[0130] Medicinal material pretreatment

[0131] Same as Example 3, all medicinal materials were washed, dried, and crushed to 80 mesh size for later use.

[0132] Water-soluble extraction

[0133] Add ginseng, ophiopogon japonicus, salvia miltiorrhiza and red peony root into the extraction tank, add purified water 12 times the weight of the medicinal materials, perform ultrasonic assisted extraction at 70°C, set the power to 200W, extract once for 20 minutes, filter and concentrate to a relative density of 1.23.

[0134] Fat-soluble extraction

[0135] 80% ethanol was added to 80% of Schisandra chinensis and Curcuma aromatica at a weight ratio of 8 times the weight of the medicinal materials. Direct heating extraction (without microwave assistance) was used at a temperature of 75°C for 25 minutes, and the extract was concentrated to a relative density of 1.20.

[0136] Mixed purification

[0137] No macroporous resin purification was performed, the water-soluble and fat-soluble extracts were directly mixed, and molecular distillation equipment was not used to remove volatile impurities.

[0138] Nanoinclusion

[0139] The extract was directly mixed with the powder without using the nano-inclusion process.

[0140] Pill forming

[0141] The same as Example 3, except that 0.1% xanthan gum and 0.05% chitosan were added as auxiliary materials, and the proportion of refined honey was 30%.

[0142] Drying and coating

[0143] The drying conditions were 40°C for 10 hours, and no coating treatment was performed.

[0144] Comparative Example 4:

[0145] Preparation process:

[0146] Medicinal material pretreatment

[0147] Same as Example 1, all medicinal materials were washed, dried, and crushed to 80 mesh size for later use.

[0148] Extraction process

[0149] Mix ginseng, ophiopogon japonicus, schisandra chinensis, salvia miltiorrhiza, red peony root, turmeric, and notoginseng powder in appropriate proportions, add 10 times the weight of the herbs in water, heat directly to 100°C, and extract for 2 hours. Filter to remove impurities, and concentrate to a relative density of 1.25.

[0150] Mixed purification

[0151] No separation and extraction of water-soluble and fat-soluble substances was performed, and the mixed extract was used directly without macroporous resin adsorption and molecular distillation purification.

[0152] Pill forming

[0153] Same as Example 1, the auxiliary material is only refined honey, the proportion is 30%, and the pills are directly made.

[0154] Drying and coating

[0155] Dry at 50℃ for 8 hours without coating.

[0156] Test Experiment

[0157] Experiment 1: Extraction efficiency comparison experiment

[0158] Sample preparation:

[0159] Example 1: Following the procedure of Example 1, water-soluble extraction (ultrasonic-assisted extraction, 70°C, 500W, 40 minutes, two extractions) and fat-soluble extraction (microwave-assisted extraction, 75% ethanol, 700W, 60°C, 15 minutes) were performed. The water-soluble extract was purified using a macroporous resin, and the fat-soluble extract was purified by molecular distillation to remove impurities.

[0160] Comparative Example 1: A single water extraction method was used without ultrasound-assisted extraction, and the extract was only heated to 70° C. for 90 minutes, with one extraction; no purification treatment was performed.

[0161] Comparative Example 4: Using the traditional boiling method, all the medicinal materials were mixed and directly heated to 100° C., and boiled in water for 2 hours without segmented extraction or purification.

[0162] Extract concentration:

[0163] The extracts of all samples were concentrated to a relative density of 1.22 (measured at 50°C).

[0164] Active ingredient content detection:

[0165] Detection method: High performance liquid chromatography (HPLC).

[0166] Target ingredients: Ginsenosides (Panax ginseng), Tanshinone (Danshen), Schisandrin A (Schisandra chinensis).

[0167] Detection conditions: A C18 chromatographic column was used, the mobile phase was acetonitrile-water gradient elution, and the detection wavelength was 254 nm.

[0168] Determine the content of target components per gram of dry sample.

[0169] Impurity content detection:

[0170] Detection method: UV-visible spectrophotometry was used to determine the total impurity content.

[0171] The absorbance of the samples was measured at a wavelength of 280 nm to estimate the impurity content.

[0172] Experimental replication:

[0173] The experiment was repeated 3 times for each sample and the average value was taken.

[0174] Experimental data

[0175] Comparison of extraction efficiency and impurity content

[0176] sample Ginsenosides (mg / g) Tanshinone (mg / g) Schisandrin A (mg / g) Impurity content (%) Example 1 18.7 25.3 12.9 4.3 Comparative Example 1 14.1 19.5 9.2 7.8 Comparative Example 4 11.8 17.4 8 9.5

[0177] This experiment demonstrated that the dual-phase extraction combined with purification technology employed in Example 1 demonstrated significant advantages in extraction efficiency and impurity control. The water-soluble extraction in Example 1 employed ultrasound-assisted technology, which enhanced cell wall disruption through ultrasonic cavitation and accelerated the release of water-soluble components such as ginsenosides and tanshinones. Traditional water extraction processes (Comparative Examples 1 and 4) relied solely on diffusion, resulting in lower extraction efficiency. Furthermore, the microwave-assisted technology used in fat-soluble extraction significantly improved the extraction efficiency of schisandrin A by directly affecting intracellular substances through the thermal and non-thermal effects of microwaves, resulting in a higher extraction rate than traditional heating methods.

[0178] The purification process in Example 1 further removed impurities after the extract was concentrated. Macroporous resin adsorption purification technology effectively separated low-molecular-weight impurities while retaining the target components, improving product purity. Molecular distillation of the fat-soluble extract further removed volatile impurities. These processes synergistically reduced the impurity content of the sample in Example 1 to 4.3%, while the impurity levels in the samples of Comparative Examples 1 and 4 reached as high as 7.8% and 9.5%, respectively, highlighting the limitations of traditional processes in effectively removing impurities.

[0179] Furthermore, the experimental results also reveal the impact of extraction time on efficiency. Comparative Examples 1 and 4 attempted to improve extraction efficiency by extending the extraction time. However, prolonged heating not only failed to significantly increase the target component content but also potentially led to degradation of some active ingredients (such as ginsenosides). In contrast, Example 1, through a short, efficient auxiliary extraction technique, avoided overheating damage and effectively preserved the integrity of the active ingredients. This demonstrates that the innovative extraction technology in Example 1 not only improves extraction efficiency but also optimizes the time cost of the process.

[0180] Experiment 2: Comparative experiment on formulation stability

[0181] Experimental procedures

[0182] Sample preparation:

[0183] Example 2: A pill sample was prepared according to the method of Example 2, with the excipients including 0.4% xanthan gum, 0.1% chitosan, and 2% β-cyclodextrin, and then subjected to film coating.

[0184] Comparative Example 2: According to the preparation method of Comparative Example 2, the amount of auxiliary materials added was reduced (xanthan gum 0.1%, chitosan 0.05%, β-cyclodextrin 1%), and no coating treatment was performed.

[0185] Comparative Example 4: According to the preparation method of Comparative Example 4, no auxiliary materials were added and the pills were directly prepared without coating treatment.

[0186] Experimental setup:

[0187] Moisture resistance test:

[0188] The samples were placed in a constant temperature and humidity chamber at a relative humidity of 75% and a temperature of 40°C for 30 days.

[0189] Weigh and record the changes in the mass of the pills every 7 days, and observe the appearance of the pills (whether they absorb moisture or disintegrate).

[0190] Antioxidant test:

[0191] HPLC was used to determine the content change rate of key active ingredients (such as ginsenosides and tanshinone) in the pills before and after storage, and samples were taken after 0 days, 15 days, and 30 days of storage.

[0192] Mechanical strength test:

[0193] The compressive strength of the pills was measured using a pill compression tester. Ten pills were tested in each group, and the maximum compressive value was recorded.

[0194] Experimental replication:

[0195] Three parallel experiments were performed for each sample group, and the average value was taken.

[0196] Data processing:

[0197] The average values ​​of mass change rate, active ingredient content change rate, and compressive strength were calculated, and the differences among the groups were analyzed.

[0198] Experimental data

[0199] Comparison of stability tests of Example 2, Comparative Examples 2 and 4.

[0200] sample Mass change rate under humidity conditions for 30 days (%) Active ingredient content change rate (%) Compressive strength (N) Example 2 1.2 -3.8 12.4 Comparative Example 2 6.7 -11.2 7.8 Comparative Example 4 12.5 -18.6 4.3

[0201] The experimental results show that the compounding of the auxiliary materials of xanthan gum, chitosan, and β-cyclodextrin in Example 2, as well as the coating treatment, significantly improved the moisture resistance, oxidation resistance, and mechanical strength of the pills. The moisture resistance test showed that the mass change rate of the sample in Example 2 was only 1.2%, far lower than that of Comparative Example 2 (6.7%) and Comparative Example 4 (12.5%). This is due to the cross-linked network structure formed by xanthan gum in a high humidity environment, which can significantly reduce the intrusion of water, thereby protecting the pills from moisture. As a biopolymer material, chitosan's adhesion and film-forming properties further enhance the surface barrier effect of the pills, effectively preventing water penetration.

[0202] Antioxidant testing further validated the protective effects of the excipients in Example 2. After 30 days of storage in a hot and humid environment, the change in the active ingredient content in Example 2 was -3.8%, significantly superior to Comparative Example 2 (-11.2%) and Comparative Example 4 (-18.6%). The inclusion complexation of β-cyclodextrin is the core mechanism for enhancing antioxidant properties. By forming an inclusion complex, it effectively isolates oxygen from direct contact with the active ingredient, significantly reducing the occurrence of oxidation reactions. Furthermore, the coating treatment forms a dense protective film on the surface of the pills, further isolating them from the effects of oxygen, moisture, and light, thereby delaying the degradation of the active ingredient.

[0203] The compressive strength of the sample in Example 2 reached 12.4N, while that of Comparative Example 2 and Comparative Example 4 was 7.8N and 4.3N, respectively. This result shows that the addition of xanthan gum and chitosan greatly enhanced the mechanical strength of the pills, making them less susceptible to breakage during transportation and storage. Xanthan gum increases the hardness of the pills by forming a cross-linked network structure with other ingredients; chitosan further enhances the toughness of the pill surface. In Comparative Examples 2 and 4, due to insufficient or missing amounts of excipients, the pills had a loose structure and significantly decreased compressive performance.

[0204] In summary, the experimental results fully verified the significant advantages of the technical solution of Example 2 from the three dimensions of moisture resistance, antioxidant resistance, and mechanical strength. The compounding of xanthan gum, chitosan, and β-cyclodextrin, combined with coating technology, forms a multi-layered protection mechanism, effectively solving the defects of traditional pills that are prone to moisture absorption, oxidation, and breakage under high humidity and long-term storage conditions, providing important technical support for the modernization and industrialization of traditional Chinese medicine preparations.

[0205] Experiment 3: Bioavailability comparison experiment

[0206] Experimental procedures

[0207] Sample preparation:

[0208] Example 3: The nano-inclusion extract was prepared according to Example 3, with an inclusion ratio of 1:1.5, and ultrasonic treatment (400 W, 20 minutes).

[0209] Comparative Example 3: The extract preparation was used directly without nano-encapsulation.

[0210] Solubility test:

[0211] The samples of Example 3 and Comparative Example 3 were added into simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 6.8), respectively, at a concentration of 0.5 mg / mL.

[0212] The concentrations of schisandrin A and tanshinone in the solution were measured at 37°C after 0, 1, 2, 4, and 6 hours, and the solubility was calculated.

[0213] In vitro release experiment:

[0214] Experimental setup: Dialysis bag method was used.

[0215] The sample (10 mg of schisandrin A content) was placed in a dialysis bag and placed in a 37°C phosphate buffer. The buffer was sampled at regular intervals (0.5 h, 1 h, 2 h, 4 h, and 6 h) to detect the content of schisandrin A in the released solution.

[0216] In vivo absorption experiment:

[0217] Experimental animals: Healthy Wistar rats were selected and randomly divided into two groups (3 groups of Example and 3 groups of Comparative Example), with 3 rats in each group.

[0218] Administration: The two groups were gavaged with the corresponding preparations, with a dose of 50 mg / kg (calculated based on schisandrin A).

[0219] Sampling time: Blood samples were collected at 0.5 h, 1 h, 2 h, 4 h, and 6 h after administration. Plasma was obtained by centrifugation and the plasma concentration of schisandrin A was determined by liquid chromatography-mass spectrometry (LC-MS / MS) to draw the pharmacokinetic curve.

[0220] Data processing:

[0221] The solubility, in vitro release rate and main pharmacokinetic parameters (Cmax, Tmax, AUC) of schisandrin A were calculated.

[0222] Each experiment was repeated 3 times and the average value was taken.

[0223] Experimental data

[0224] Comparison of solubility, release rate and pharmacokinetics between Example 3 and Comparative Example 3.

[0225] sample Solubility (mg / mL, 6h) In vitro release rate (%, 6h) Cmax (ng / mL) Tmax(h) AUC0-6 (ng·h / mL) Example 3 1.72 83.5 432.7 1 1793.6 Comparative Example 3 0.95 58.6 267.3 2 1024.4

[0226] The experimental results show that the nanoinclusion technology in Example 3 significantly improves the solubility and bioavailability of the fat-soluble active ingredient schisandrin A. Solubility testing shows that the solubility of the sample in Example 3 in simulated gastric fluid after 6 hours is 1.72 mg / mL, which is 1.8 times that of Comparative Example 3. This is because the nanoinclusion technology encapsulates the fat-soluble molecules within the β-cyclodextrin molecular structure, increasing the water solubility of the active ingredient through its external hydrophilic molecular skeleton, thereby significantly improving the solubility of the poorly soluble component in the aqueous medium.

[0227] In vitro release experiments further validated the improved release rate of the active ingredient achieved through nanoinclusion technology. The release rate of the sample in Example 3 reached 83.5% after 6 hours, nearly 25% higher than the 58.6% in Comparative Example 3. This demonstrates that nanoinclusion technology not only enhances solubility but also promotes the release of the active ingredient in solution. This improvement is primarily attributed to the reduced particle size and increased surface area of ​​the inclusion complex, which improves its dispersibility in the buffer solution and enhances the release effect.

[0228] In vivo absorption experiments showed that the peak blood drug concentration (Cmax) of the samples in Example 3 was significantly higher than that in Comparative Example 3, and the peak time of onset (Tmax) was advanced by one hour, indicating that the nanoinclusion technology significantly improved the absorption rate of schisandrin A. Furthermore, the AUC0-6 (area under the curve) showed that the overall bioavailability of the Example 3 group was approximately 75% higher than that of Comparative Example 3. This result demonstrates that nanoinclusion technology, by improving solubility and release behavior, enables faster and more complete absorption of schisandrin A in the gastrointestinal tract, thereby increasing the efficiency of drug utilization in the body.

[0229] Nanoinclusion technology relies on the unique molecular structure of β-cyclodextrin, whose hydrophobic cavity effectively encapsulates fat-soluble ingredients while exposing the hydrophilic groups to the aqueous environment, thereby improving the dispersibility and stability of fat-soluble molecules. This mechanism significantly improves the solubility and absorption of schisandrin A and tanshinone in Example 3. However, due to the lack of an inclusion process, the fat-soluble ingredients in Comparative Example 3 have poor solubility in aqueous media, limiting their absorption rate and efficiency.

[0230] In summary, this experiment verified the significant advantages of the nanoinclusion technology of Example 3 in improving the bioavailability of fat-soluble active ingredients from the three dimensions of solubility, in vitro release rate and pharmacokinetics, providing strong support for the technological innovation of the present invention.

[0231] Experiment 4: Preliminary evaluation of treatment effects

[0232] Experimental procedures

[0233] Animal model establishment:

[0234] Animal grouping: Healthy male Wistar rats weighing 180-220 g were randomly divided into the following three groups, with 10 rats in each group:

[0235] Blank group: fed with normal basal feed without drug intervention;

[0236] Group 2 of Example 2 was administered orally with the pills prepared in Example 2 at a dose of 50 mg / kg;

[0237] Comparative Example 4 group: Orally administered with the pills prepared in Comparative Example 4 at a dose of 50 mg / kg.

[0238] Model establishment: Except for the blank group, the other two groups were fed a high-fat diet (basic diet + cholesterol 1% + lard 10%) for 4 weeks and intraperitoneally injected with isoproterenol (85 mg / kg) to establish hyperlipidemia and myocardial ischemia models.

[0239] Dosage:

[0240] According to the group treatment, drug intervention began after the model was established, with oral administration once a day for 30 consecutive days.

[0241] Test content:

[0242] Blood lipid level test:

[0243] Blood was collected from the rat tail vein every 10 days, and the serum was separated to detect the concentrations of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) in the serum (unit: mmol / L).

[0244] Myocardial protection index detection:

[0245] After 30 days, at the end of the experiment, serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities were measured by cardiac blood sampling (unit: U / L).

[0246] Cardiac pathology observations:

[0247] The rat hearts were dissected and stained with HE. The myocardial cell arrangement, inflammatory infiltration and necrosis were observed under a microscope.

[0248] Experimental replication:

[0249] Each test was repeated 3 times and the average value was taken.

[0250] Data processing:

[0251] The inter-group differences in blood lipid levels, myocardial enzyme indicators and pathological results were statistically analyzed to analyze the therapeutic effect of Example 2.

[0252] Experimental data

[0253] Comparison of therapeutic effects between Example 2 and Comparative Example 4

[0254] index Blank group Example 2 group Comparative Example 4 TC (mmol / L) 2.3±0.2 3.1±0.3 4.8±0.5 TG (mmol / L) 0.9±0.1 1.4±0.2 2.2±0.4 LDL-C (mmol / L) 0.8±0.1 1.1±0.2 1.8±0.3 LDH (U / L) 256±15 398±23 472±31 CK(U / L) 138±10 287±18 345±25

[0255] The experimental results show that the Example 2 group has significant advantages in lowering blood lipid levels and protecting myocardial function. Blood lipid indicators show that the TC, TG and LDL-C levels of the Example 2 group are significantly lower than those of the Comparative Example 4 group, with a decrease of 35.4%, 36.4% and 38.9% respectively. This improvement effect is due to the synergistic effect of the coenzyme and tanshinone in Example 2. The former significantly reduces the deposition of blood lipids in the blood vessel wall by promoting lipid metabolism; the latter has anti-inflammatory and endothelial function-improving effects, thereby further improving the balance of blood lipid metabolism. However, since Comparative Example 4 does not use modern preparation technology, the content of key active ingredients is insufficient, and its blood lipid improvement effect is weak.

[0256] Myocardial protection indicators further verified the cardiac protection advantages of Example 2. LDH and CK levels are sensitive biochemical indicators of myocardial damage. The LDH and CK levels of the Example 2 group were 398U / L and 287U / L, respectively, which were significantly lower than the 472U / L and 345U / L of the Comparative Example 4 group. This shows that the Example 2 preparation is more effective in alleviating myocardial ischemic damage. In Example 2, chitosan and β-cyclodextrin significantly improved the bioavailability of the drug by synergistically protecting the key components, thereby reducing the degree of damage to myocardial cells under ischemic conditions. On the contrary, due to the lack of protective excipients, the bioavailability of the active ingredient of the drug in Comparative Example 4 is low, and the therapeutic effect is limited.

[0257] Cardiac pathology observations also showed that the cardiomyocytes in the Example 2 group were more regularly arranged, with only mild inflammatory cell infiltration and occasional necrotic areas. In contrast, the cardiomyocytes in the Comparative Example 4 group were disorderly arranged, with significantly larger necrotic areas and more severe inflammatory infiltration. This difference further confirms the significant effect of Example 2 in protecting myocardial structure and function.

[0258] The remarkable results achieved in Example 2 are due to modern preparation techniques that fully extract and stabilize the drug ingredients. Ultrasonic-assisted extraction and macroporous resin purification effectively concentrate active ingredients such as tanshinone and ginsenosides, making their pharmacological effects more pronounced. Nanoinclusion technology enhances the solubility and bioavailability of fat-soluble ingredients such as schisandrin, allowing them to reach the site of action more quickly and fully, thereby achieving comprehensive improvements in cardiovascular function. In comparison, Comparative Example 4, due to its use of traditional water-boiling methods, has lower extraction efficiency and active ingredient content, resulting in significantly inferior therapeutic effects.

[0259] While embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions, and variations may be made to these embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the appended claims and their equivalents.

Claims

1. A Guanxin Shengmai Pill, characterized in that: In parts by weight, it is prepared from the following raw materials: 7-12 parts of ginseng, 7-12 parts of ophiopogon, 2-5 parts of schisandra, 12-20 parts of salvia, 10-15 parts of red peony root, 7-12 parts of turmeric, 0.4-0.8 parts of notoginseng powder; The following excipients are further added based on the total weight of the medicinal materials: Xanthan gum 0.2%-0.5%, chitosan 0.1%-0.3%, β-cyclodextrin 1%-2%, refined honey 30%-50%; Among them: Ginseng, Ophiopogon japonicus and Salvia miltiorrhiza were extracted by water-soluble extraction to obtain extracts; Schisandra chinensis and Curcuma aromatica were extracted by fat-soluble extraction to obtain extracts; Panax notoginseng powder was directly added as fine powder; Prepared by the following steps: Medicinal material pretreatment: Weigh ginseng, ophiopogon japonicus, schisandra chinensis, salvia miltiorrhiza, red peony root, turmeric and notoginseng powder according to the ratio. Except for notoginseng powder, wash, dry and grind the remaining medicinal materials into fine powder for later use; Water-soluble extraction: Ginseng, Ophiopogon japonicus, Salvia miltiorrhiza and Paeonia lactiflora are subjected to water-soluble extraction, and after filtering to remove impurities, the water-soluble extract is concentrated to obtain a water-soluble extract; Fat-soluble extraction: Perform fat-soluble extraction on Schisandra chinensis and Curcuma aromatica, recover the solvent and concentrate it to obtain a fat-soluble extract; Mixed purification: The water-soluble extract is purified by an adsorption purification device, and the fat-soluble extract is removed from impurities by a separation device to obtain a high-purity extract; Nano-inclusion: The extract is mixed with the inclusion material to form a stable inclusion compound; Pill forming: Mix the extract with medicinal material powder and excipients, add forming materials, and prepare pills in a pill making device; Drying and coating: Dry the pills and apply a protective film on the surface of the pills to obtain the finished product; The extraction of Schisandra chinensis and Curcuma aromatica adopts a fat-soluble extraction method, adding 70% to 80% ethanol, and the microwave extraction conditions are power 600 to 800W, temperature 50 to 70°C, and time 10 to 20 minutes; wherein the fat-soluble extract is subjected to a rotary evaporator to remove ethanol and is concentrated to a relative density of 1.15 to 1.20; The nano-inclusion process uses ultrasonic conditions with a power of 300 to 500 W for 15 to 25 minutes, and the inclusion ratio is 1:1.5 to 1:2 between the water-soluble and fat-soluble extracts and β-cyclodextrin. The proportion of refined honey added during pill molding is 35% to 45% of the total weight of the medicinal powder, and the stirring time is 20 to 30 minutes; The drying process is carried out at a temperature of 50 to 60°C and a drying time of 8 to 12 hours, and the moisture content of the final pellets is controlled at ≤8%. The concentration of the hydroxypropyl methylcellulose solution used in the coating process is 0.5% to 1%, the coating temperature is 40 to 50°C, and the coating is continued to dry for 2 to 4 hours; Among them, the extraction of ginseng, ophiopogon, salvia miltiorrhiza and red peony root adopts water-soluble extraction method, adding 8 to 12 times the weight of purified water, and performing ultrasonic assisted extraction at 70 to 80°C, with an ultrasonic power of 400 to 600W and an extraction time of 30 to 50 minutes.

2. The method for preparing Guanxin Shengmai Pills according to claim 1, characterized in that: The water-soluble extract is filtered through a 200-mesh filter to remove large particle impurities, and is concentrated to a relative density of 1.20 to 1.25 using a vacuum concentration device.

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