Coronary heart pulse-activating pill and preparation method thereof

Abstract

The invention relates to the technical field of traditional Chinese medicine preparations, and discloses a coronary heart pulse-activating pill which comprises the following raw material components in parts by weight: 7-12 parts of ginseng, 7-12 parts of radix ophiopogonis, 2-5 parts of schisandra chinensis, 12-20 parts of salvia miltiorrhiza, 10-15 parts of radix paeoniae rubra, 7-12 parts of radix curcumae and 0.4-0.8 part of pseudo-ginseng powder. Based on the total weight of the medicinal materials, the composition also comprises the following auxiliary materials in percentage by weight: 0.2 to 0.5 percent of xanthan gum, 0.1 to 0.3 percent of chitosan, 1 to 2 percent of beta-cyclodextrin and 30 to 50 percent of refined honey. By adopting a two-phase extraction technical scheme of combining water-soluble extraction and fat-soluble extraction, segmented extraction is performed according to the characteristics of water-soluble components (such as ginsenoside and tanshinone) and fat-soluble components (such as schizandrin and curcumin) respectively, and adsorption purification and molecular distillation technologies are introduced, so that the extraction rate of key active components is increased by 30-40%, the extraction time is shortened, and the extraction cost is reduced. Meanwhile, the technical effect of reducing impurity interference is achieved, and the defects that the content of effective components is insufficient and the drug effect is unstable are overcome.

Description

Technical Field

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

[0002] Cardiovascular disease is one of the major causes of death and disability worldwide, and its incidence rate is increasing year by year. In particular, hyperlipidemia and coronary heart disease have become major chronic diseases that threaten human health. Traditional treatment options mainly include two methods: Western medicine treatment: represented by statins, aspirin and other drugs, works by lowering blood lipid levels, resisting thrombosis and improving vascular function.

[0003] Interventional surgery: including coronary artery stenting and bypass surgery, which restore blood vessel patency through mechanical means.

[0004] In recent years, traditional Chinese medicine has received extensive attention in the auxiliary treatment of cardiovascular diseases because of its multi-target and low side effect characteristics, especially in the long-term management of chronic diseases. However, there are still many problems in the development and application of traditional Chinese medicine preparations. The extraction process of traditional Chinese medicine preparations is mainly water boiling extraction, and single heating extraction is prone to insufficient release of ingredients. For example, key ingredients such as ginsenosides and tanshinone are released slowly at low temperatures, and high-temperature extraction may cause the degradation of some active ingredients.

[0005] In the existing technology, the extraction of fat-soluble components (such as schisandrin A and tanshinone) is more difficult, and 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.

[0006] 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.

[0007] 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 consistency in product quality and difficulty in meeting the standards of modern Chinese medicine preparations. Summary of the invention

[0008] 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.

[0009] To achieve the above objectives, the present invention is implemented by the following technical scheme: A Guanxin Shengmai Pill, comprising the following raw material components by weight: 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 curcuma, 0.4-0.8 parts of notoginseng powder; The following excipients are also included 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%.

[0010] A method for preparing Guanxin Shengmai Pills comprises the following steps: Pretreatment of medicinal materials: weigh ginseng, ophiopogon japonicus, schisandra chinensis, salvia miltiorrhiza, red peony root, curcuma and notoginseng powder according to the proportion. Except for notoginseng powder, wash, dry and grind the remaining medicinal materials into fine powder for later use; Water-soluble extraction: extract ginseng, ophiopogon japonicus, salvia miltiorrhiza and red peony root by water-soluble extraction, filter to remove impurities, and concentrate to obtain 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 the medicinal powder and excipients, add the forming material, and prepare pills in a pill making device; Drying and coating: The pills are dried and a protective film is coated on the surface of the pills to obtain the finished product.

[0011] 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.

[0012] 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 800 W, temperature 50 to 70° C., and time 10 to 20 minutes.

[0013] 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.

[0014] 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 is 1:1.5 to 1:2 of water-soluble and fat-soluble extracts to β-cyclodextrin.

[0015] 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.

[0016] 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%.

[0017] 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.

[0018] Preferably, the extraction of ginseng, ophiopogon japonicus, salvia miltiorrhiza and red peony root adopts a 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.

[0019] The present invention provides a Guanxin Shengmai Pill and a preparation method thereof, which has the following beneficial effects: 1. The present invention adopts a dual-phase extraction technology scheme combining water-soluble extraction with fat-soluble extraction. By performing segmented extraction according to the characteristics of water-soluble components (such as ginsenosides and tanshinone) and fat-soluble components (such as schisandrin A and curcumin), and introducing adsorption purification and molecular distillation technology, the extraction rate of key active ingredients is increased by 30%-40%, while reducing the interference of impurities. Compared with the traditional single extraction method in the prior art, the problems of low extraction efficiency and high impurity content are solved, which solves the problems of insufficient content of active ingredients and unstable efficacy.

[0020] 2. The present invention adopts a compounding technical scheme of functional excipients such as xanthan gum, chitosan and β-cyclodextrin, and improves the molding strength and moisture resistance of the pills through xanthan gum, chitosan realizes the sustained release function, and β-cyclodextrin improves the stability and solubility of fat-soluble components through inclusion technology, achieving the technical effect of significantly improving the stability and storage performance of the drug. Compared with the problem of fragile, moisture-absorbing or deteriorating finished drugs due to the single excipient in the prior art, the problem of insufficient storage performance of the pills is solved.

[0021] 3. The present invention combines the design of segmented extraction and refined purification to achieve the technical effect of significantly improving the content of key active ingredients and the consistency between product batches. Compared with the problem of obvious differences in product quality batches due to many extracted impurities and large process fluctuations in the prior art, the problem of unstable product quality in the preparation of traditional Chinese medicine is solved.

[0022] 4. The present invention adopts a design scheme combining nano-inclusion and chitosan sustained-release technology. The solubility of fat-soluble components is improved by nano-inclusion, and chitosan achieves sustained-release effect, achieving the technical effect of increasing the bioavailability of effective components by 2 times. Compared with the technical schemes in the prior art with low absorption rate and poor effective utilization rate of insoluble components in drugs, the problem of insufficient utilization rate of traditional Guanxin Shengmai Pills is solved. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 It is a flow chart of the preparation method of the present invention. DETAILED DESCRIPTION

[0024] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. 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 creative work are within the scope of protection of the present invention.

[0025] Please see attached Figure 1 : Example

[0026] Example 1

[0027] Raw materials and formula Main ingredients: Ginseng: 10g Ophiopogon japonicus: 10g Schisandra chinensis: 4g Salvia miltiorrhiza: 18g Red peony root: 13g Curcuma: 10g Panax notoginseng powder: 0.6g Excipients: Xanthan gum: 0.3% (based on the total weight of medicinal materials) Chitosan: 0.2% (based on the total weight of medicinal materials) β-cyclodextrin: 1.5% (based on the total weight of medicinal materials) Refined honey: 40% (based on the total weight of medicinal material powder) Preparation steps: Pretreatment of medicinal materials: Wash ginseng, ophiopogon japonicus, schisandra chinensis, salvia miltiorrhiza, red peony root and curcuma, dry them at 50°C to a moisture content of ≤10%, and then crush them into 80 mesh for later use. Panax notoginseng powder is directly added in proportion for later use.

[0028] Water-soluble extraction: Add ginseng, Ophiopogon japonicus, Salvia miltiorrhiza and Paeonia lactiflora to the extraction tank, add purified water at 10 times the weight of the medicinal materials, and perform ultrasonic assisted extraction at 70°C, with the power set to 500W for 40 minutes. Extract twice, combine the extracts, filter to remove large particle impurities, and concentrate to a relative density of 1.22 (measured at 50°C).

[0029] Fat-soluble extraction: 75% ethanol was added to 8 times the weight of Schisandra chinensis and Curcuma zedoariae, and extracted for 15 minutes at a microwave power of 700 W and a temperature of 60°C. The extract was concentrated to a relative density of 1.18 after the ethanol was recovered by a rotary evaporator.

[0030] Mixed purification The water-soluble extract was adsorbed by a macroporous resin, eluted with 30% ethanol, and the eluate was collected and concentrated.

[0031] The fat-soluble extract is passed through a molecular distillation device to remove volatile impurities and obtain a high-purity extract.

[0032] 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.

[0033] Pill Forming: The nano inclusion compound was evenly mixed with powder, xanthan gum and chitosan, 40% refined honey and an appropriate amount of water were added, and pills with a diameter of about 4 mm were prepared by a pill making machine.

[0034] Drying and coating: Dry the pills at 55°C for 10 hours to make the water content ≤8%. Then use 0.8% hydroxypropyl methylcellulose solution for coating at 45°C and continue drying for 3 hours after coating.

[0035] Summary of Examples This example uses a two-phase extraction combined with purification technology to significantly improve the extraction rate of key active ingredients (such as ginsenosides, tanshinone, schisandrin A, etc.), especially by optimizing the ultrasonic conditions during the water-soluble extraction process, which increases the extraction efficiency by about 30%. Thanks to the precise control of fat-soluble extraction, the purity of the extract is increased by about 25% compared with the traditional method, greatly reducing impurities.

[0036] Embodiment 2: Raw materials and formula Main ingredients: Ginseng: 9g, Ophiopogon japonicus: 8g, Schisandra chinensis: 3g, Salvia miltiorrhiza: 15g, Red Peony Root: 12g, Curcuma aromatica: 9g, Panax notoginseng powder: 0.5g Excipients: xanthan gum: 0.4% (based on the total weight of medicinal materials), chitosan: 0.1% (based on the total weight of medicinal materials), β-cyclodextrin: 2% (based on the total weight of medicinal materials), refined honey: 45% (based on the total weight of medicinal material powder) Preparation steps: Pretreatment of medicinal materials After all the medicinal materials are cleaned, they are dried at 50°C to a moisture content of ≤10%, and crushed to 100 mesh for later use.

[0037] Water soluble extraction Ginseng, Ophiopogon japonicus, Salvia miltiorrhiza and Paeonia lactiflora were added into purified water at 10 times of the weight of the medicinal materials, and ultrasonic extraction was performed at 75°C, power 450W, time 35 minutes. After filtering and removing impurities, the extract was concentrated to a relative density of 1.20.

[0038] Lipid-soluble extraction The Schisandrae Chinensis and Curcuma Radix were extracted with 70% ethanol, microwave power was 650W, temperature was 55℃, time was 12 minutes. The extract was concentrated to a relative density of 1.16.

[0039] Mixed purification The water-soluble extract is adsorbed by macroporous resin and eluted with 40% ethanol. The fat-soluble extract is passed through molecular distillation equipment to remove impurities.

[0040] Nano-inclusion 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.

[0041] Pill Forming All extracts were mixed with medicinal material powder, xanthan gum, chitosan and refined honey to prepare water-honey pills with a diameter of 5 mm.

[0042] Drying and coating After drying at 55°C for 12 hours, the film was coated with 1% hydroxypropyl methylcellulose solution at 50°C and dried for 2 hours.

[0043] This embodiment adopts the compounding technology of xanthan gum and chitosan to enhance the moisture resistance of the preparation and significantly improve the mechanical strength, thus solving the problem of fragility and moisture absorption of traditional pills. At the same time, the inclusion technology of β-cyclodextrin further improves the stability of the ingredients. Experiments show that the shelf life of the pills is extended by 30% compared with that of Example 1.

[0044] Embodiment 3: Raw materials and formula Main ingredients: Ginseng: 8g, Ophiopogon japonicus: 7g, Schisandra chinensis (fried with vinegar): 4g, Salvia miltiorrhiza: 16g, Red Peony Root: 14g, Curcuma aromatica: 11g, Panax notoginseng powder: 0.7g Excipients: xanthan gum: 0.2% (based on the total weight of medicinal materials), chitosan: 0.3% (based on the total weight of medicinal materials), β-cyclodextrin: 1% (based on the total weight of medicinal materials), refined honey: 35% (based on the total weight of medicinal material powder) Preparation steps Pretreatment of medicinal materials All medicinal materials were washed, dried to a moisture content of ≤10%, and crushed to 80 mesh.

[0045] Water soluble extraction Add 12 times the weight of the medicinal material with water, perform ultrasonic extraction at 70°C, 500W, for 50 minutes, and concentrate to a relative density of 1.23.

[0046] Lipid-soluble extraction Schisandra chinensis and Curcuma aromatica were extracted by adding 75% ethanol at 8 times their weight, with microwave power of 750 W, temperature of 65° C., time of 18 minutes, and concentrated to a relative density of 1.17.

[0047] Mixed purification The extract is purified and distilled to obtain high-purity components.

[0048] Nano-inclusion The nanoencapsulation ratio was set to 1:1.5, the ultrasonic power was 400 W, and the time was 20 min.

[0049] Pill Forming The nano inclusion compound is mixed with the powder, and refined honey and auxiliary materials are added to make pills with a diameter of 3 mm.

[0050] Drying and coating Dry at 50°C for 8 hours, apply 0.5% hydroxypropyl methylcellulose coating and dry for 3 hours.

[0051] Summary of Examples This embodiment combines chitosan and nano-inclusion technology to increase the solubility of poorly soluble components (such as schisandrin A) by 2 times, and significantly enhances bioavailability. Compared with Examples 1 and 2, this embodiment is more suitable for the long-term use needs of patients with chronic diseases.

[0052] Comparative Example Comparative Example 1: Preparation process: Pretreatment of medicinal materials Same as Example 1, all medicinal materials were washed, dried, and crushed to 80 mesh for later use.

[0053] Water soluble extraction Ginseng, Ophiopogon japonicus, Salvia miltiorrhiza and Paeonia lactiflora were added to the extraction tank, and purified water was added at 10 times the weight of the medicinal materials. The extraction was directly heated at 70°C without ultrasonic assistance. The extraction time was set to 90 minutes, and the extraction was repeated once. After filtering and removing impurities, the extract was concentrated to a relative density of 1.22.

[0054] Lipid-soluble extraction As in Example 1, 75% ethanol microwave extraction was used for Schisandrae Chinensis and Curcuma Aromatica 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.

[0055] Mixed purification The water-soluble extract is directly mixed with the fat-soluble extract without being purified by macroporous resin.

[0056] Nano-inclusion No nanoencapsulation was performed, and the extracts were directly mixed and used for pelleting.

[0057] Pill Forming 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.

[0058] Drying and coating Same as Example 1, except that the drying conditions were 55° C., the time was 10 hours, and the coating process was the same.

[0059] Comparative Example 2: Preparation process: Pretreatment of medicinal materials Same as Example 2, all medicinal materials were washed, dried, and crushed to 100 mesh for later use.

[0060] Water soluble extraction Same as in Example 2, ultrasonic assisted extraction was adopted, with a power of 450 W and a time of 35 minutes, and the product was concentrated to a relative density of 1.20 after filtration.

[0061] Lipid-soluble extraction As in Example 2, Schisandra chinensis and Curcuma aromatica were extracted by microwave using 70% ethanol, with a microwave power of 650 W, a temperature of 55° C., and a time of 12 minutes.

[0062] Mixed purification The water-soluble extract and the fat-soluble extract are directly mixed without purification using macroporous resin and molecular distillation equipment.

[0063] Nano-inclusion 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.

[0064] Pill Forming 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%.

[0065] Drying and coating The mixture was dried at 50°C for 6 hours (shorter than the recommended drying time in the example) using a 0.2% hydroxypropyl methylcellulose solution.

[0066] Comparative Example 3: Preparation process: Pretreatment of medicinal materials Same as Example 3, all medicinal materials were washed, dried, and crushed to 80 mesh for later use.

[0067] Water soluble extraction 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, and concentrate to a relative density of 1.23 after filtering.

[0068] Lipid-soluble extraction 80% ethanol was added to schisandra chinensis and curcuma zedoaria at 8 times the weight of the medicinal materials, and direct heating extraction (without microwave assistance) was used. The temperature was set at 75°C and the time was 25 minutes. The extract was concentrated to a relative density of 1.20.

[0069] Mixed purification No macroporous resin purification was performed, the water-soluble and fat-soluble extracts were directly mixed, and no molecular distillation equipment was used to remove volatile impurities.

[0070] Nano-inclusion The nano-inclusion process was not used, and the extract was directly mixed with the powder.

[0071] Pill Forming The same as Example 3, the auxiliary materials xanthan gum 0.1%, chitosan 0.05% were added, and the proportion of refined honey was 30%.

[0072] Drying and coating The drying conditions were 40°C for 10 hours, and no coating treatment was performed.

[0073] Comparative Example 4: Preparation process: Pretreatment of medicinal materials Same as Example 1, all medicinal materials were washed, dried, and crushed to 80 mesh for later use.

[0074] Extraction process Mix ginseng, ophiopogon japonicus, schisandra chinensis, salvia miltiorrhiza, red peony root, curcuma and notoginseng powder in proportion, add water 10 times the weight of the medicinal materials, heat directly to 100℃ and extract for 2 hours. Filter and remove impurities, and concentrate to a relative density of 1.25.

[0075] Mixed purification 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.

[0076] Pill Forming Same as in Example 1, the auxiliary material is only refined honey, the proportion is 30%, and the pills are directly made.

[0077] Drying and coating Dry at 50℃ for 8 hours without coating treatment.

[0078] Test experiment Experiment 1: Extraction efficiency comparison experiment Sample preparation: Example 1: According to the process of Example 1, water-soluble extraction (ultrasonic assisted extraction, 70°C, 500W, 40 minutes, 2 extractions) and fat-soluble extraction (microwave assisted extraction, 75% ethanol, 700W, 60°C, 15 minutes) were performed respectively. The water-soluble extract was purified by macroporous resin, and the fat-soluble extract was decontaminated by molecular distillation.

[0079] Comparative Example 1: A single water extraction method was used without ultrasound-assisted extraction, and the mixture was only heated to 70° C. for extraction for 90 minutes, with one extraction; no purification treatment was performed.

[0080] Comparative Example 4: Using the traditional boiling method, all the medicinal materials were mixed and directly heated to 100° C., and boiled for 2 hours without segmented extraction or purification.

[0081] Extract concentration: The extracts of all samples were concentrated to a relative density of 1.22 (measured at 50°C).

[0082] Active ingredient content detection: Detection method: Using high performance liquid chromatography (HPLC).

[0083] Target ingredients: Ginsenosides (Panax ginseng), Tanshinone (Danshen), Schisandrin A (Schisandra chinensis).

[0084] Detection conditions: C18 chromatographic column, acetonitrile-water gradient elution as mobile phase, detection wavelength 254nm.

[0085] Determine the content of target ingredients per gram of dry sample.

[0086] Impurity content detection: Detection method: UV-visible spectrophotometry was used to determine the total impurity content.

[0087] The absorbance of the samples was measured at a wavelength of 280 nm to estimate the impurity content.

[0088] Experimental replication: The experiment was repeated 3 times for each sample and the average value was taken.

[0089] Experimental data Comparison of extraction efficiency and impurity content 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 This experiment shows that the two-phase extraction combined with purification technology used in Example 1 shows significant advantages in extraction efficiency and impurity control. The water-soluble extraction in Example 1 uses ultrasonic-assisted technology, which increases the degree of cell wall rupture through ultrasonic cavitation effect and accelerates the release of water-soluble components such as ginsenosides and tanshinone, while the traditional water extraction process (Comparative Example 1, Comparative Example 4) only relies on diffusion, resulting in low extraction efficiency. At the same time, the microwave-assisted technology used in fat-soluble extraction directly acts on intracellular substances through the thermal and non-thermal effects of microwaves, significantly improving the extraction efficiency of schisandrin A, and the extraction rate is higher than that of traditional heating methods.

[0090] The purification process of Example 1 further removes impurities after the extract is concentrated. The macroporous resin adsorption purification technology can effectively separate low molecular weight impurities while retaining the target components, thereby improving the purity of the product; the fat-soluble extract is further removed by molecular distillation to remove volatile impurities. These processes work synergistically to reduce the impurity content of the sample in Example 1 to 4.3%, while the impurity content in the samples of Comparative Examples 1 and 4 is as high as 7.8% and 9.5%, respectively, reflecting the disadvantage of traditional processes that it is difficult to effectively remove impurities.

[0091] In addition, the experimental results also reflect the effect of extraction time on efficiency. Comparative Examples 1 and 4 attempted to improve the extraction efficiency by extending the extraction time, but long-term heating not only failed to significantly increase the content of the target component, but also may cause the degradation of some active ingredients (such as ginsenosides). In contrast, Example 1 avoided overheating damage and effectively retained the integrity of the active ingredients through short-time and efficient auxiliary extraction technology. This shows that the innovative extraction technology in Example 1 not only improves the extraction efficiency, but also optimizes the time cost of the process.

[0092] Experiment 2: Comparative experiment on the stability of preparations Experimental procedures Sample preparation: Example 2: A pill sample was prepared according to the method of Example 2, wherein the excipients included 0.4% xanthan gum, 0.1% chitosan, and 2% β-cyclodextrin, and a coating process was performed.

[0093] 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.

[0094] 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.

[0095] Experimental setup: Moisture resistance test: 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.

[0096] 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).

[0097] Antioxidant test: 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.

[0098] Mechanical strength test: The compressive strength of the pills was measured using a pill compression tester. Ten pills were tested in each group, and the maximum pressure value was recorded.

[0099] Experimental replication: Three parallel experiments were performed for each group of samples, and the average value was taken.

[0100] Data processing: 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.

[0101] Experimental data Comparison of stability tests of Example 2, Comparative Example 2 and Comparative Example 4.

[0102] 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 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, have significantly improved the moisture resistance, antioxidant properties and mechanical strength of the pills. The moisture resistance test shows that the mass change rate of the sample in Example 2 is only 1.2%, which is much 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 moisture, thereby protecting the pills from moisture. As a biopolymer material, chitosan's adhesion and film formation properties further enhance the surface barrier effect of the pills, effectively preventing moisture penetration.

[0103] The antioxidant test further verified the protective effect of the excipients in Example 2. After storage in a hot and humid environment for 30 days, the change rate of the active ingredient content in Example 2 was -3.8%, which was significantly better than Comparative Example 2 (-11.2%) and Comparative Example 4 (-18.6%). The inclusion complex of β-cyclodextrin is the core mechanism for improving antioxidant properties. It effectively isolates the direct contact between oxygen and the active ingredient by forming an inclusion complex, significantly reducing the occurrence of oxidation reactions. At the same time, the coating treatment further isolates the influence of oxygen, moisture and light by forming a dense protective film on the surface of the pills, thereby delaying the degradation of the active ingredient.

[0104] 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 enhances the mechanical strength of the pills, making them less susceptible to damage 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. Due to insufficient or missing amounts of excipients in Comparative Examples 2 and 4, the pills have loose structures and significantly reduced compressive properties.

[0105] In summary, the experimental results fully verified the significant advantages of the technical solution of Example 2 from the three dimensions of moisture resistance, oxidation resistance and mechanical strength. The compounding of the auxiliary materials of xanthan gum, chitosan and β-cyclodextrin, combined with the coating technology, formed a multi-level protection mechanism, which effectively solved the defects of traditional pills that are easy to absorb moisture, oxidize and break under high humidity and long-term storage conditions, and provided important technical support for the modernization and industrialization of traditional Chinese medicine preparations.

[0106] Experiment 3: Bioavailability comparison experiment Experimental procedures Sample preparation: 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 min).

[0107] Comparative Example 3: The extract preparation was used directly without nano-encapsulation.

[0108] Solubility test: 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.

[0109] 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.

[0110] In vitro release experiment: Experimental setup: Dialysis bag method was used.

[0111] 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, 6 h) to detect the content of schisandrin A in the released solution.

[0112] In vivo absorption experiment: 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.

[0113] Administration: The two groups were gavaged with the corresponding preparations, with the dose of 50 mg / kg (calculated based on schisandrin A).

[0114] Sampling time: Blood samples were collected at 0.5h, 1h, 2h, 4h, and 6h after administration, and plasma was obtained by centrifugation. The blood concentration of schisandrin A was determined by liquid chromatography-mass spectrometry (LC-MS / MS), and the pharmacokinetic curve was drawn.

[0115] Data processing: The solubility, in vitro release rate and main pharmacokinetic parameters (Cmax, Tmax, AUC) of schisandrin A were calculated.

[0116] Each group of experiments was repeated 3 times and the average value was taken.

[0117] Experimental data The solubility, release rate and pharmacokinetics of Example 3 were compared with those of Comparative Example 3.

[0118] 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 The experimental results show that the nano-inclusion technology in Example 3 significantly improves the solubility and bioavailability of the fat-soluble active ingredient Schisandrin A. The solubility test 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 nano-inclusion technology encapsulates the fat-soluble molecules in the molecular structure of β-cyclodextrin, and increases the water solubility of the active ingredients through its external hydrophilic molecular skeleton, thereby significantly improving the solubility of the poorly soluble components in the aqueous medium.

[0119] The in vitro release experiment further verified the improvement of the release rate of active ingredients by nano-inclusion technology. The release rate of the sample in Example 3 reached 83.5% after 6 hours, which was nearly 25% higher than that of Comparative Example 3 (58.6%). This shows that nano-inclusion technology not only improves solubility, but also promotes the release of active ingredients in solution. This improvement is mainly attributed to the reduction of inclusion compound particle size and the increase of surface area, which makes the inclusion compound have better dispersibility in the buffer solution and enhances the release effect.

[0120] 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 (Tmax) was advanced by 1 hour, indicating that the nano-inclusion technology significantly improved the absorption rate of Schisandrin A. At the same time, AUC0-6 (area under the curve) showed that the overall bioavailability of Example 3 was about 75% higher than that of Comparative Example 3. This result shows that the nano-inclusion technology improves the solubility and release behavior, allowing Schisandrin A to be absorbed more quickly and fully in the gastrointestinal tract, thereby improving the utilization efficiency of the drug in the body.

[0121] Nano-inclusion technology lies in the special molecular structure of β-cyclodextrin, whose hydrophobic cavity can effectively encapsulate fat-soluble components and expose hydrophilic groups to the water environment, thereby improving the dispersibility and stability of fat-soluble molecules. This mechanism significantly improves the solubility and absorption performance of Schisandrin A and Tanshinone in Example 3, while in Comparative Example 3, due to the lack of inclusion process, the solubility of fat-soluble components in water medium is poor, and the absorption rate and efficiency are limited.

[0122] In summary, this experiment verified the significant advantages of the nanoencapsulation 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 technical innovation of the present invention.

[0123] Experiment 4: Preliminary evaluation of treatment effect Experimental procedures Animal model establishment: Animal grouping: Healthy male Wistar rats weighing 180-220 g were randomly divided into the following three groups, with 10 rats in each group: Blank group: fed with normal basal feed without drug intervention; Example 2 group: gavage with the pills prepared in Example 2, with a dose of 50 mg / kg; Comparative Example 4 group: The pellets prepared in Comparative Example 4 were intragastrically administered at a dose of 50 mg / kg.

[0124] Model establishment: Except for the blank group, the other two groups were fed with 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.

[0125] Dosage: According to the group treatment, drug intervention began after the model was established, with oral administration once a day for 30 consecutive days.

[0126] Test content: Blood lipid level test: Blood was collected from rat tail vein every 10 days, and serum was separated to detect the concentrations of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) in serum (mmol / L).

[0127] Myocardial protection index detection: After 30 days, at the end of the experiment, the activities of serum lactate dehydrogenase (LDH) and creatine kinase (CK) were measured by cardiac blood sampling at the end of the experiment (unit: U / L).

[0128] Cardiac pathological observations: The rat hearts were dissected and stained with HE, and the arrangement of myocardial cells, inflammatory infiltration and necrosis were observed under a microscope.

[0129] Experimental replication: Each test was repeated 3 times and the average value was taken.

[0130] Data processing: 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.

[0131] Experimental data Comparison of therapeutic effects between Example 2 and Comparative Example 4 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 The experimental results show that the Example 2 group has significant advantages in reducing 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, which are reduced by 35.4%, 36.4% and 38.9% respectively. This improvement effect is due to the synergistic effect of 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.

[0132] 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 Example 2 group were 398U / L and 287U / L, respectively, which were significantly lower than 472U / L and 345U / L of Comparative Example 4 group. This shows that the preparation of Example 2 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, Comparative Example 4 has a low bioavailability of the active ingredients of the drug and limited therapeutic effect.

[0133] The results of cardiac pathological observation also showed that the myocardial cells of Example 2 group were arranged more regularly, with only mild inflammatory cell infiltration and occasional necrotic areas, while the myocardial cells of Comparative Example 4 group were arranged disorderly, with a significantly larger necrotic area and more severe inflammatory infiltration. This difference further confirmed the significant effect of Example 2 in protecting myocardial structure and function.

[0134] The remarkable effect of Example 2 is due to the full extraction and stability protection of the drug ingredients by modern preparation technology. Ultrasonic assisted extraction and macroporous resin purification technology effectively concentrate active ingredients such as tanshinone and ginsenosides, making their pharmacological effects more significant; nano-inclusion technology improves the solubility and bioavailability of fat-soluble ingredients such as schisandra alcohol A, allowing them to reach the site of action faster and more fully, thereby achieving a comprehensive improvement in cardiovascular function. In comparison, due to the use of traditional water boiling method, the extraction efficiency and active ingredient content of Comparative Example 4 are both low, and its therapeutic effect is significantly inferior.

[0135] Although 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 the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A Guanxin Shengmai Pill, characterized in that: In parts by weight, it includes the following raw material components: 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 curcuma, 0.4-0.8 parts of notoginseng powder; The following excipients are also included 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%; in: Extracts of ginseng, ophiopogon japonicus and salvia miltiorrhiza were obtained by water-soluble extraction; Extracts of Schisandra chinensis and Curcuma zedoaria were obtained by fat-soluble extraction; Panax notoginseng powder can be added directly and used as fine powder.

2. A method for preparing Guanxin Shengmai Pills, according to the Guanxin Shengmai Pills according to claim 1, characterized in that: The following steps are involved: Pretreatment of medicinal materials: weigh ginseng, ophiopogon japonicus, schisandra chinensis, salvia miltiorrhiza, red peony root, curcuma and notoginseng powder according to the proportion. Except for notoginseng powder, wash, dry and grind the remaining medicinal materials into fine powder for later use; Water-soluble extraction: extract ginseng, ophiopogon japonicus, salvia miltiorrhiza and red peony root by water-soluble extraction, filter to remove impurities, and concentrate to obtain 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 the medicinal powder and excipients, add the forming material, and prepare pills in a pill making device; Drying and coating: The pills are dried and a protective film is coated on the surface of the pills to obtain the finished product.

3. The method for preparing Guanxin Shengmai Pills according to claim 2, 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.

4. The method for preparing Guanxin Shengmai Pills according to claim 1, characterized in that: The extraction of Schisandra chinensis and Curcuma aromatica adopts a fat-soluble extraction method, adds 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.

5. The method for preparing Guanxin Shengmai Pills according to claim 4, characterized in that: 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.

6. The method for preparing Guanxin Shengmai Pills according to claim 2, characterized in that: The nano inclusion process uses ultrasonic conditions with a power of 300-500W for 15-25 minutes, and the inclusion ratio is 1:1.5-1:2 between water-soluble and fat-soluble extracts and beta-cyclodextrin.

7. The method for preparing Guanxin Shengmai Pills according to claim 2, characterized in that: When the pills are formed, the proportion of refined honey added is 35% to 45% of the total weight of the medicinal material powder, and the stirring time is 20 to 30 minutes.

8. The method for preparing Guanxin Shengmai Pills according to claim 2, characterized in that: 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%.

9. The method for preparing Guanxin Shengmai Pills according to claim 1, characterized in that: 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.

10. The method for preparing Guanxin Shengmai Pills according to claim 2, characterized in that: The extraction of ginseng, ophiopogon, salvia miltiorrhiza and red peony root adopts water-soluble extraction method, adds 8 to 12 times the weight of purified water, performs 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.

Images