A method for improving the transfer rate of berberine hydrochloride in Shuangshi Tonglin Capsules

Abstract

The present invention belongs to the technical field of material extraction methods, and relates to a method for improving the transfer rate of berberine hydrochloride in Shuangshi Tonglin Capsules. During the preparation of Shuangshi Tonglin Capsules, by regulating the mass ratio of the amount of decocted water of Phellodendron amurense Rupr. var. sutchuenense Schneid. to the amount of Phellodendron amurense Rupr. var. sutchuenense Schneid., and the pH value of the decocted water of Phellodendron amurense Rupr. var. sutchuenense Schneid., the transfer rate of berberine hydrochloride in the capsules is increased; the greater the mass ratio, the higher the transfer rate of berberine hydrochloride in the capsules; the more acidic the pH value of the water, the higher the transfer rate of berberine hydrochloride in the capsules. The present invention can regulate the transfer rate of berberine hydrochloride in the capsules to 88.2%, achieving the purpose of cost reduction, efficiency improvement and quality control.

Description

Technical Field

[0001] The present invention belongs to the technical field of material extraction methods, and relates to a method for improving the transfer rate of berberine hydrochloride in Shuangshi Tonglin Capsules. Background Art

[0002] Shuangshi Tonglin Capsules, a proprietary Chinese medicine produced by Shaanxi Modemeide Qixuehe Pharmaceutical Co., Ltd., with the national drug approval number Z20080028, is a capsule preparation. Its main ingredients include: Cortex Phellodendri Chinensis, Rhizoma Dioscoreae Hypoglaucae, Herba Patriniae, Indigo Naturalis, Talcum, Semen Plantaginis, Rhizoma Acori Tatarinowii, Poria, Rhizoma Atractylodis and Radix Salviae Miltiorrhizae. Its main functions are to clear heat and promote diuresis, and to eliminate turbidity and promote urination.

[0003] One of the main ingredients in Shuangshi Tonglin Capsules, berberine hydrochloride, has inhibitory effects on Bacillus dysenteriae, Escherichia coli, Diplococcus pneumoniae, Staphylococcus aureus, Streptococcus, Salmonella typhi and Entamoeba histolytica. Clinically, it is mainly used for intestinal infections and bacillary dysentery, etc. It is also found that this product has the effect of anti-arrhythmia; berberine has strong anti-tumor activity in vivo and in vitro and can induce the differentiation of B16 cells; it has a synergistic effect with cytarabine hydrochloride in vitro.

[0004] The existing preparation process of Shuangshi Tonglin Capsules is as follows: Cortex Phellodendri Chinensis is decocted with water three times, for 1.5 hours for the first time, and 1 hour for the second and third times. The decoction liquids are combined and filtered; Atractylodes lancea and Acorus tatarinowii are distilled to extract volatile oils. The volatile oils are included with β-cyclodextrin, the inclusion complex is dried, pulverized into coarse powder and reserved. The aqueous solution after distillation is collected separately in another container; Radix Salviae Miltiorrhizae is extracted with 80% ethanol twice, for 1 hour each time. The extraction liquids are combined and filtered, and the ethanol is recovered until there is no alcohol smell and reserved; its residue, Rhizoma Dioscoreae Hypoglaucae, Herba Patriniae, Semen Plantaginis, Talcum and Poria are decocted with water twice, for 1.5 hours each time. The decoction liquids are combined and filtered; the above-mentioned various medicinal liquids are combined, concentrated into a thick paste, added with Indigo Naturalis, dried, pulverized, added with 5% - 15% starch, granulated and dried; added with the coarse powder of the β-cyclodextrin inclusion complex, mixed evenly, filled into capsules to make 1000 capsules, and that's it.

[0005] In the current preparation process of Shuangshi Tonglin Capsules, the decoction liquid obtained from decocting Cortex Phellodendri Chinensis is mixed with other traditional Chinese medicines for concentration and filtration, resulting in unstable transfer rate of berberine hydrochloride, and the transfer rate of berberine hydrochloride is relatively low, only reaching 42.4%, which cannot fully exert the medicinal efficacy. On the other hand, it also increases the input of raw materials, raises the cost and reduces losses. Summary of the Invention

[0006] The purpose of the present invention is to provide a method for improving the transfer rate of berberine hydrochloride in Shuangshi Tonglin Capsules, and to regulate and increase the transfer rate of berberine hydrochloride to 88.2%, so as to achieve the purpose of cost reduction, efficiency increase and quality control.

[0007] In order to achieve the above purpose, the solution adopted by the present invention is:

[0008] A method for improving the transfer rate of berberine hydrochloride in Shuangshi Tonglin Capsules. During the preparation of Shuangshi Tonglin Capsules, by regulating the mass ratio of the amount of water used for decocting Phellodendri Chinensis Schneid. and the amount of Phellodendri Chinensis Schneid., and the pH value of the water used for decocting Phellodendri Chinensis Schneid., the transfer rate of berberine hydrochloride in the capsules is increased.

[0009] Furthermore, the greater the mass ratio of the amount of water used for decocting Phellodendri Chinensis Schneid. to the amount of Phellodendri Chinensis Schneid., the higher the transfer rate of berberine hydrochloride in the capsules.

[0010] Furthermore, for every 6-fold increase in the mass ratio of the amount of water used for decocting Phellodendri Chinensis Schneid. to the amount of Phellodendri Chinensis Schneid., the transfer rate of berberine hydrochloride in the capsules increases by 5.7%.

[0011] Furthermore, the more acidic the pH value of the water, the higher the transfer rate of berberine hydrochloride in the capsules.

[0012] Furthermore, for every 1.0 decrease in the pH value of the water from 7.0, the transfer rate of berberine hydrochloride in the capsules increases by 9.6% - 9.7%.

[0013] Furthermore, when the mass ratio of the amount of water used for decocting Phellodendri Chinensis Schneid. to the amount of Phellodendri Chinensis Schneid. is 32:1 and the pH of the water is 5.0, the transfer rate of berberine hydrochloride in the capsules is 88.2%.

[0014] Furthermore, Phellodendri Chinensis Schneid. is decocted three times, and after each decoction and boiling, a circulation is carried out every 30 minutes for 10 minutes each time.

[0015] Furthermore, in the Shuangshi Tonglin Capsules, the mass percentage of Phellodendri Chinensis Schneid. is 7.4%.

[0016] The beneficial effects of the present invention are as follows:

[0017] 1. The present invention optimizes the preparation process of Shuangshi Tonglin Capsules. During each decoction of Phellodendri Chinensis Schneid., a circulation is carried out, and the filtrate of Phellodendri Chinensis Schneid. is concentrated separately. At the same time, the amount of water used for decoction and the acidity of the water are controlled, so that the transfer rate of berberine hydrochloride in the capsules is increased to 88.2%; compared with the existing transfer rate of 44.2%, the transfer rate of berberine hydrochloride in the present invention is increased by nearly one time at most, providing data support for the large-scale production of Shuangshi Tonglin Capsules and having application prospects.

[0018] 2. The mechanism of regulating the transfer rate of berberine hydrochloride in the present invention is that, according to the properties of berberine hydrochloride in Phellodendri Chinensis Schneid., berberine hydrochloride is a quaternary ammonium alkaloid, which is easily soluble in hot water, and the free form has a relatively large solubility in water. At the same time, its solubility increases under acidic conditions; by regulating the appropriate amount of added water, berberine hydrochloride in the medicinal materials can be extracted to the greatest extent. At the same time, by adjusting the acidity of the water and increasing its solubility, berberine hydrochloride in the medicinal materials can be fully extracted, further improving the transfer rate of berberine hydrochloride.

[0019] 3. Through the research on improving the transfer rate of berberine hydrochloride, the present invention can also internally control the quality of the decocting water and the water quality in the preparation process, reduce the procurement difficulty, and lower the raw material cost. Detailed Embodiments

[0020] The present invention will be described in detail below in conjunction with embodiments.

[0021] A method for improving the transfer rate of berberine hydrochloride in Shuangshi Tonglin Capsules. During the preparation of Shuangshi Tonglin Capsules, by regulating the mass ratio of the amount of decocting water of Phellodendron amurense Rupr. var. sutchuenense Schneid. to the amount of Phellodendron amurense Rupr. var. sutchuenense Schneid. and the pH value of the decocting water of Phellodendron amurense Rupr. var. sutchuenense Schneid., the transfer rate of berberine hydrochloride in the capsules is increased.

[0022] In the present invention, the larger the mass ratio of the amount of decocting water of Phellodendron amurense Rupr. var. sutchuenense Schneid. to the amount of Phellodendron amurense Rupr. var. sutchuenense Schneid., the higher the transfer rate of berberine hydrochloride in the capsules.

[0023] In the present invention, for every 6-fold increase in the mass ratio of the amount of decocting water of Phellodendron amurense Rupr. var. sutchuenense Schneid. to the amount of Phellodendron amurense Rupr. var. sutchuenense Schneid., the transfer rate of berberine hydrochloride in the capsules increases by 5.7%.

[0024] In the present invention, the more acidic the pH value of the water, the higher the transfer rate of berberine hydrochloride in the capsules.

[0025] In the present invention, for every 1.0 decrease in the pH value of the water from 7.0, the transfer rate of berberine hydrochloride in the capsules increases by 9.6% - 9.7%.

[0026] In the present invention, the mass ratio of the amount of decocting water of Phellodendron amurense Rupr. var. sutchuenense Schneid. to the amount of Phellodendron amurense Rupr. var. sutchuenense Schneid. is 32:1, the pH of the water is 5.0, and the transfer rate of berberine hydrochloride in the capsules is 88.2%.

[0027] In the present invention, the decoction of Phellodendron amurense Rupr. var. sutchuenense Schneid. is carried out three times, and after each boiling of Phellodendron amurense Rupr. var. sutchuenense Schneid., circulation is carried out once every 30 minutes for 10 minutes each time.

[0028] The following illustrates the method for increasing the transfer rate of berberine hydrochloride in Shuangshi Tonglin Capsules through specific embodiments.

[0029] First, in Shuangshi Tonglin Capsules, the mass ratios of each raw material are as follows:

[0030] The mass ratios of Phellodendron amurense Rupr. var. sutchuenense Schneid., Salvia miltiorrhiza Bunge, Dioscorea septemloba Thunb., Patrinia scabiosaefolia Fisch. ex Trevir., Plantago asiatica L., Talcum, Poria cocos (Schw.) Wolf, Atractylodes lancea (Thunb.) DC., Acorus tatarinowii Schott, and Indigo naturalis are 16:32:32:32:32:19:16:16:16:5 respectively.

[0031] The preparation method of Shuangshi Tonglin Capsules includes the following steps:

[0032] 1) Add water to Phellodendron amurense Rupr. var. sachalinense (Schott) Nakai three times for decoction. After each boiling, circulate for 10 minutes once every 30 minutes, and combine the decoction liquids of the three times to obtain the medicinal liquid; the decoction times for the three times are 1.5 hours, 1 hour, and 1 hour in sequence.

[0033] In this step, the specific steps of adding water for decoction three times are as follows: For the first decoction, add water to the raw material Phellodendron amurense Rupr. var. sachalinense (Schott) Nakai for decoction for 1.5 hours, and filter to obtain the first filtrate and the first medicinal residue; for the second decoction, add water to the first medicinal residue for decoction for 1 hour to obtain the second filtrate and the second medicinal residue; for the third decoction, add water to the second medicinal residue for decoction for 1 hour to obtain the third filtrate and the third medicinal residue, and combine the first filtrate, the second filtrate, and the third filtrate to obtain the medicinal liquid.

[0034] 2) After the medicinal liquid in step 1) is filtered, pump it into a rotary evaporator, and collect the material when concentrated under reduced pressure to more than 2 times the amount of the Phellodendron amurense Rupr. var. sachalinense (Schott) Nakai medicinal materials to obtain the clear extract of Phellodendron amurense Rupr. var. sachalinense (Schott) Nakai; the medicinal liquid is filtered under 100 meshes; the pressure for concentration under reduced pressure is -0.06 MPa to 0.09 MPa.

[0035] 3) Select Salvia miltiorrhiza Bunge, Dioscorea hypoglauca Palib., Patrinia scabiosaefolia Fisch. ex Link, Plantago asiatica L., Talcum, Poria cocos (Schw.) Wolf, Atractylodes lancea (Thunb.) DC., and Acorus tatarinowii Schott, and prepare a mixed clear extract, an ethanol extract clear extract, and a filtrate.

[0036] The specific steps of step 3) of the present invention are as follows:

[0037] 3.1) Add ethanol to Salvia miltiorrhiza Bunge for decoction twice. The addition amount of ethanol for both times is 6 times the mass of Salvia miltiorrhiza Bunge, and decoct for 1 hour each time; combine the extraction liquids of the two times and filter to obtain the medicinal residue and the ethanol extract;

[0038] 3.2) Recover ethanol from the ethanol extract in step 3.1) until odorless to obtain the ethanol extract clear extract;

[0039] 3.3) Mix Dioscorea hypoglauca Palib., Patrinia scabiosaefolia Fisch. ex Link, Plantago asiatica L., Talcum, Poria cocos (Schw.) Wolf with the medicinal residue in step 3.1) to obtain a mixture; add water to the mixture for decoction twice. For the first time, add water 12 times the mass of the mixture for decoction for 1.5 hours; for the second time, add water 10 times the mass of the mixture for decoction for 1.5 hours, combine the decoction liquids and filter, and concentrate at 50 °C to a relative density of 1.15 - 1.20 to obtain the mixed clear extract;

[0040] 3.4) Add water to Atractylodes lancea (Thunb.) DC. and Acorus tatarinowii Schott for decoction for 5 hours. The added mass of water is 5 times the total mass of Atractylodes lancea (Thunb.) DC. and Acorus tatarinowii Schott, and filter the decoction liquid to obtain the filtrate and the volatile oil.

[0041] In this step, the method of decoction twice can refer to the first two times of adding water for decoction of Phellodendron amurense Rupr. var. sachalinense (Schott) Nakai. The difference is that 80% ethanol is added for decoction in Salvia miltiorrhiza Bunge.

[0042] The volatile oil is included by β-cyclodextrin, and the inclusion compound is dried and pulverized into coarse powder.

[0043] 4) Mix the Phellodendron amurense Rupr. clear paste, the mixed clear paste, the ethanol-extracted clear paste and the filtrate, and concentrate to obtain a thick paste.

[0044] In this step, the concentration temperature is 70 °C, and it is concentrated to a relative density of 1.32 - 1.35.

[0045] 5) After adding indigo naturalis to the thick paste and mixing evenly, successively carry out vacuum drying, pulverization, and sieving to obtain a mixed powder, and then add β-cyclodextrin inclusion complex (coarse powder) to obtain Shuangshi Tonglin Capsules.

[0046] In this step, the vacuum drying time is 8 h, and the pulverization particle size is 40 mesh.

[0047] Example 1

[0048] In this example, the method for improving the transfer rate of berberine hydrochloride in Shuangshi Tonglin Capsules includes the following steps:

[0049] 1) Cut the Phellodendron amurense Rupr. decoction pieces (silk about 0.5 cm wide and about 3 - 8 cm long) into small pieces with a particle size of 1 cm - 2 cm; take 200 g of the 1 cm - 2 cm small pieces of Phellodendron amurense Rupr., decoct with water three times, circulate for 10 min each time at intervals of 30 min after each boiling, and combine the decoction liquids (i.e., the filtrates of each decoction) to obtain a medicinal liquid.

[0050] In this step, the specific steps of decocting with water three times are as follows: For the first decoction, add water to the raw material Phellodendron amurense Rupr. and decoct for 1.5 h, filter to obtain the first filtrate and the first medicinal residue; for the second decoction, add water to the first medicinal residue and decoct for 1 h to obtain the second filtrate and the second medicinal residue; for the third decoction, add water to the second medicinal residue and decoct for 1 h to obtain the third filtrate and the third medicinal residue, and combine the first filtrate, the second filtrate and the third filtrate to obtain a medicinal liquid.

[0051] In this example, the mass ratio of the total mass of water for decocting to the mass of Phellodendron amurense Rupr. decoction pieces is 32:1, that is, the water addition amount is 32 times the mass of Phellodendron amurense Rupr., and during the three decoctions, for the first time, add 12 times the amount of water of Phellodendron amurense Rupr. and decoct for 1.5 h, for the second time, add 10 times the amount of water of Phellodendron amurense Rupr. and decoct for 1 h; for the third time, add 10 times the amount of water of Phellodendron amurense Rupr. and decoct for 1 h.

[0052] In this example, the pH of water is 7, and the water is drinking water.

[0053] 2) After filtering the medicinal liquid in step 1) through a 100-mesh sieve, pump it into a rotary evaporator, and under a pressure of -0.06 MPa - 0.09 MPa and a temperature of 70 °C, carry out vacuum concentration and collect the material when it is more than 2 times the amount of Phellodendron amurense Rupr. medicinal materials to obtain Phellodendron amurense Rupr. clear paste.

[0054] 3) Select Salvia miltiorrhiza, Dioscorea hypoglauca, Patrinia scabiosaefolia, Plantago asiatica, Talc, Poria cocos, Atractylodes lancea and Acorus tatarinowii, and prepare a mixed clear extract, an ethanol extract and a filtrate.

[0055] The specific steps in this example are as follows:

[0056] 3.1) Add ethanol to Salvia miltiorrhiza and decoct twice. The amount of ethanol added each time is 6 times the mass of Salvia miltiorrhiza, and decoct for 1 h each time; Combine the extraction liquids of the two times and filter to obtain medicinal residues and an ethanol extract.

[0057] 3.2) Recover ethanol from the ethanol extract in step 3.1) until odorless to obtain an ethanol extract.

[0058] 3.3) Mix Dioscorea hypoglauca, Patrinia scabiosaefolia, Plantago asiatica, Talc, Poria cocos with the medicinal residues in step 3.1) to obtain a mixture; Add water to the mixture and decoct twice. For the first time, add 12 times the mass of the mixture of water and decoct for 1.5 h; For the second time, add 10 times the mass of the mixture of water and decoct for 1.5 h. Combine the decoction liquids and filter, and concentrate at 50 °C to a relative density of 1.15 - 1.20 to obtain a mixed clear extract.

[0059] 3.4) Add water to Atractylodes lancea and Acorus tatarinowii and decoct for 5 h. The amount of water added is 5 times the total mass of Atractylodes lancea and Acorus tatarinowii. Filter the decoction liquid to obtain a filtrate.

[0060] In this step, the decoction method for the two times can refer to the first two times of adding water and decocting of Phellodendron amurense Rupr. The difference is that 80% ethanol is added to Salvia miltiorrhiza for decocting.

[0061] 4) Mix the Phellodendron amurense Rupr. clear extract, the mixed clear extract, the ethanol extract and the filtrate, and concentrate at 70 °C to a relative density of 1.32 - 1.35 to obtain a thick extract.

[0062] 5) Add Indigo Naturalis to the thick extract and mix well, then successively carry out vacuum drying for 8 h to obtain a dry extract; Crush the dry extract to 40 meshes, sieve to obtain a mixed powder, and then add β - cyclodextrin inclusion complex to obtain Shuangshi Tonglin Capsules. The vacuum drying temperature is 70 °C.

[0063] Example 2

[0064] Different from Example 1, in this example, the pH of water is 6 and the water is purified water.

[0065] Example 3

[0066] Different from Example 1, in this example, the pH of water is 5 and the water is drinking water.

[0067] Example 4

[0068] Different from Example 1, in this example, the Cortex Phellodendri Amurensis is Cortex Phellodendri Amurensis cut pieces, without cutting, that is, filaments about 0.5 cm wide and about 3 cm to 8 cm long.

[0069] Example 5

[0070] Different from Example 1, in this example, the Cortex Phellodendri Amurensis cut pieces are cut into small pieces with a particle size of 0.8 cm to 1 cm, and less than 1 cm.

[0071] For Examples 1 to 5, the content of berberine hydrochloride in the medicinal liquid obtained in step 1) and the dry extract in step 5) was detected. The detection method was the HPLC method adopted by the existing industry. Further, the transfer rate of berberine hydrochloride was calculated. The results are shown in Table 1.

[0072] Table 1 Detection results of Examples 1 to 5

[0073]

[0074] It can be seen from Table 1 that under the same conditions, the more acidic the pH value of water is, the higher the transfer rate of berberine hydrochloride is. And when the pH value of water decreases by 1 from 7, the transfer rate of berberine hydrochloride in the decoction of Cortex Phellodendri Amurensis increases by 9.4 - 9.7%, and the transfer rate of berberine hydrochloride in the final dry extract (i.e., capsules) increases by 9.6 - 9.7%. Therefore, it is best to use slightly acidic water for extraction during the production process.

[0075] Under the same conditions, the extraction transfer rate of small pieces of Cortex Phellodendri Amurensis with a size of 0.8 cm to 1 cm and less than 1 cm (Example 5) is slightly higher by 0.8% than that of small pieces of Cortex Phellodendri Amurensis with a size of 1 cm to 2 cm (Example 1), and the extraction transfer rate of small pieces of Cortex Phellodendri Amurensis with a size of 1 cm to 2 cm (Example 1) is slightly higher by 1.4% than that of Cortex Phellodendri Amurensis cut pieces (Example 4). It can be seen that the particle size of Cortex Phellodendri Amurensis has little effect on the transfer rate of berberine hydrochloride. Although the smaller the particle size, the higher the transfer rate, small pieces of particles are not conducive to production operations during the production process. Therefore, considering comprehensively, Cortex Phellodendri Amurensis cut pieces with a particle size of 1 cm to 2 cm are selected as the production specification.

[0076] Example 6

[0077] In this example, the method for increasing the transfer rate of berberine hydrochloride in Shuangshi Tonglin Capsules includes the following steps:

[0078] 1) Take 500 g of Cortex Phellodendri Amurensis cut pieces, decoct with water in three times. After each boiling, circulate for 1 time every 30 min, and each circulation is 10 min. Combine the decoction liquids (i.e., the filtrates of each decoction) to obtain the medicinal liquid.

[0079] In this step, the specific steps of decocting with water three times are as follows: For the first decoction, water is added to the raw material Phellodendri Chinensis Cortex and decocted for 1.5 h, and then filtered to obtain the first filtrate and the first medicinal residues; for the second decoction, water is added to the first medicinal residues and decocted for 1 h to obtain the second filtrate and the second medicinal residues; for the third decoction, water is added to the second medicinal residues and decocted for 1 h to obtain the third filtrate and the third medicinal residues. The first filtrate, the second filtrate and the third filtrate are combined to obtain the medicinal liquid.

[0080] In this example, the mass ratio of the total mass of water used for decocting to the mass of the Phellodendri Chinensis Cortex decoction pieces is 38:1, that is, the amount of water added is 38 times the mass of the Phellodendri Chinensis Cortex. And during the three decoctions, for the first time, water with a dosage 14 times that of the Phellodendri Chinensis Cortex is added and decocted for 1.5 h; for the second time, water with a dosage 12 times that of the Phellodendri Chinensis Cortex is added and decocted for 1 h; for the third time, water with a dosage 12 times that of the Phellodendri Chinensis Cortex is added and decocted for 1 h.

[0081] In this example, the pH of the water is 7 and the water is purified water.

[0082] 2) After the medicinal liquid in step 1) is filtered through a 100-mesh sieve, it is pumped into a rotary evaporator and concentrated under reduced pressure at a pressure of -0.06 MPa to 0.09 MPa and a temperature of 70 °C. When it is concentrated to more than 2 times the amount of the Phellodendri Chinensis Cortex medicinal material, the material is collected to obtain the Phellodendri Chinensis Cortex clear extract.

[0083] 3) Salvia miltiorrhiza, Dioscoreae Hypoglaucae Rhizoma, Patriniae Herba, Plantaginis Semen, Talci Pulvis, Poria, Atractylodis Rhizoma and Acori Tatarinowii Rhizoma are selected to prepare a mixed clear extract, an ethanol extract clear extract and a filtrate.

[0084] The specific steps in this example are as follows:

[0085] 3.1) Ethanol is added to Salvia miltiorrhiza and decocted twice. The amount of ethanol added each time is 6 times the mass of Salvia miltiorrhiza, and it is decocted for 1 h each time; the extraction liquids of the two times are combined and filtered to obtain the medicinal residues and the ethanol extract;

[0086] 3.2) The ethanol in the ethanol extract in step 3.1) is recovered until odorless to obtain the ethanol extract clear extract;

[0087] 3.3) Dioscoreae Hypoglaucae Rhizoma, Patriniae Herba, Plantaginis Semen, Talci Pulvis and Poria are mixed with the medicinal residues in step 3.1) to obtain a mixture; water is added to the mixture and decocted twice. For the first time, water with a mass 12 times that of the mixture is added and decocted for 1.5 h; for the second time, water with a mass 10 times that of the mixture is added and decocted for 1.5 h. The decoction liquids are combined and filtered, and concentrated to a relative density of 1.15 - 1.20 at 50 °C to obtain the mixed clear extract;

[0088] 3.4) Water is added to Atractylodis Rhizoma and Acori Tatarinowii Rhizoma and decocted for 5 h. The mass of water added is 5 times the total mass of Atractylodis Rhizoma and Acori Tatarinowii Rhizoma, and the decoction liquid is filtered to obtain the filtrate.

[0089] In this step, the method of decocting twice can refer to the first two times of adding water to decoct Phellodendri Chinensis Schneid. The difference is that 80% ethanol is added for decocting danshen (Salvia miltiorrhiza Bunge).

[0090] 4) Mix the clear paste of Phellodendri Chinensis Schneid, the mixed clear paste, the ethanol-extracted clear paste and the filtrate, and concentrate at 70°C to a relative density of 1.32 - 1.35 to obtain a thick paste.

[0091] 5) Add indigo naturalis to the thick paste and mix evenly, then successively carry out vacuum drying for 8 h to obtain a dry paste; crush the dry paste to 40 mesh, sieve to obtain a mixed powder, and then add β-cyclodextrin inclusion complex to obtain Shuangshi Tonglin Capsules. The vacuum drying temperature is 70°C.

[0092] Example 7

[0093] Different from Example 6, in this example, the mass ratio of the total mass of the water for decocting to the mass of the Phellodendri Chinensis Schneid cut pieces is 32:1, that is, the water addition amount is 32 times the mass of Phellodendri Chinensis Schneid. And during the three times of decocting, for the first time, add water with a dosage of 12 times that of Phellodendri Chinensis Schneid and decoct for 1.5 h; for the second time, add water with a dosage of 10 times that of Phellodendri Chinensis Schneid and decoct for 1 h; for the third time, add water with a dosage of 10 times that of Phellodendri Chinensis Schneid and decoct for 1 h.

[0094] Example 8

[0095] Different from Example 6, in this example, the mass ratio of the total mass of the water for decocting to the mass of the Phellodendri Chinensis Schneid cut pieces is 26:1, that is, the water addition amount is 26 times the mass of Phellodendri Chinensis Schneid. And during the three times of decocting, for the first time, add water with a dosage of 10 times that of Phellodendri Chinensis Schneid and decoct for 1.5 h; for the second time, add water with a dosage of 8 times that of Phellodendri Chinensis Schneid and decoct for 1 h; for the third time, add water with a dosage of 8 times that of Phellodendri Chinensis Schneid and decoct for 1 h.

[0096] Detect the content of berberine hydrochloride in the medicinal liquid obtained in step 1) and the dry paste obtained in step 5) in Examples 6 - 8. The detection method is the HPLC method adopted by the existing industry, and further calculate the transfer rate of berberine hydrochloride. The results are shown in Table 2.

[0097] Table 2 Detection results of Examples 6 - 8

[0098]

[0099] It can be seen from Table 2 that under the same conditions, the greater the water addition amount of Phellodendri Chinensis Schneid, the higher the transfer rate of berberine hydrochloride. And for every increase of 6 times, the transfer rate of berberine hydrochloride in the decocted medicinal liquid of Phellodendri Chinensis Schneid increases by 4.5 - 7.6%, and the transfer rate of berberine hydrochloride in the final dry paste (capsules) increases by 5.7%.

[0100] Although more water is better, it was also found that when the quality of the decocting water is 32 times that of the Cortex Phellodendri Amurensis, and the water is added three times in amounts of 12 times - 10 times - 10 times respectively, the transfer rate of berberine hydrochloride can reach over 65%. Considering energy consumption comprehensively, the preferred corresponding amounts of water added for the three decoctions are at least 12 times, 10 times, and 10 times, that is, the water consumption is at least 32 times.

[0101] Examples 9 - 11

[0102] The methods of Examples 9 - 11 refer to the method of Example 1, using Cortex Phellodendri Amurensis cut pieces. The difference is the reduced pressure temperature of the Cortex Phellodendri Amurensis medicinal liquid in step 2) and the vacuum drying temperature of the dry extract in step 5) (the specific temperature values are shown in Table 3), and finally capsules are prepared.

[0103] For Examples 9 - 11, the content of berberine hydrochloride in the medicinal liquid obtained in step 1) and the dry extract in step 5) was detected. The detection method was the HPLC method adopted in the existing industry, and the transfer rate of berberine hydrochloride was further calculated. The results are shown in Table 3.

[0104] Table 3 Detection Results of Examples 9 - 11

[0105]

[0106]

[0107] Referring to Table 3, when both the reduced pressure concentration temperature and the vacuum drying temperature decrease, the transfer rate of berberine hydrochloride increases. And for every 5°C decrease, the transfer rate of berberine hydrochloride in the Cortex Phellodendri Amurensis medicinal liquid increases by 0.7% - 0.9%, and the transfer rate of berberine hydrochloride in the dry extract (capsules) increases by 1.8% - 2.3%. The reduced pressure concentration temperature and the vacuum drying temperature have little effect on the transfer rate.

[0108] The existing preparation process of Shuangshi Tonglin Capsules: Cortex Phellodendri Amurensis cut pieces are decocted with water 3 times. The first decoction is for 1.5 hours, and the second and third decoctions are for 1 hour; the decoction liquids are combined and filtered; after collecting the materials and mixing them evenly with the Salvia miltiorrhiza concentrated liquid and other water - extracted concentrated liquids, they are further concentrated under reduced pressure to a thick paste, and after adding Indigo Naturalis, they are dried under reduced pressure and vacuum; the transfer rate of berberine hydrochloride in the obtained capsules is 44.2%.

[0109] Preparation process of the Shuangshi Tonglin Capsule of the present invention: Cut the Cortex Phellodendri Chinensis decoction pieces into small particles with a particle size of 1 cm to 2 cm, soak them in acid water with pH = 5 and then decoct them 3 times. The water consumption for decoction is 32 times the mass of Cortex Phellodendri Chinensis. When decocting three times, add 12 times water for the first time and decoct for 1.5 hours, and add 10 times water each for the second and third times and decoct for 1 hour; the pH of the water is 5, and force a circulation once every 30 minutes after each boiling, and the circulation lasts for 10 minutes; filter the medicinal liquid while it is hot through a 100-mesh sieve, concentrate the filtered liquid separately, control the concentration temperature at 70 °C and concentrate to the specified amount (more than 2 times the amount of the medicinal materials), collect the materials, mix and stir evenly with the concentrated liquid of Salvia miltiorrhiza and other water-extracted concentrated liquids, and then continue to concentrate under reduced pressure at 70 °C to a thick paste with a relative density of 1.30 to 1.35 (70 °C). After adding Indigo Naturalis and mixing, control the filling amount per plate at 1.0 to 1.3 kg, set the reduced-pressure vacuum drying at 70 °C for 8 hours. The extraction transfer rate of berberine hydrochloride in the obtained dry paste (capsule) is 88.2%, which is 1 time higher than the existing extraction transfer rate of berberine hydrochloride of 44.2%.

[0110] In summary, in the preparation of the capsule of the present invention, a circulation is carried out during each decoction process of Cortex Phellodendri Chinensis, and the filtrate of Cortex Phellodendri Chinensis is concentrated separately. At the same time, each parameter is regulated to regulate the decoction water and the acidity and alkalinity of the water to improve the transfer rate of berberine hydrochloride, and the transfer rate can be regulated up to 88.2%; compared with the existing extraction transfer rate of berberine hydrochloride of 44.2%, it is 1 time higher, providing data support for the large-scale production of the Shuangshi Tonglin Capsule, carrying out internal control on the raw material quality, reducing the procurement difficulty, reducing the raw material cost, and having an application prospect.

Claims

1. A method for improving the transfer rate of berberine hydrochloride in Shuangshi Tonglin Capsules, characterized in that, During the preparation of Shuangshi Tonglin Capsules, the Cortex Phellodendri Amurensis is circulated during each decoction process, and the filtrate of Cortex Phellodendri Amurensis is concentrated separately; and by regulating the mass ratio of the amount of water used for decocting Cortex Phellodendri Amurensis to the amount of Cortex Phellodendri Amurensis, and the pH of the water for decocting Cortex Phellodendri Amurensis, the transfer rate of berberine hydrochloride in the capsules is increased; the mass ratio of the amount of water used for decocting Cortex Phellodendri Amurensis to the amount of Cortex Phellodendri Amurensis is 32:1, the pH of the water is 5.0, and the transfer rate of berberine hydrochloride in the capsules is 88.2%. The mass ratios of each raw material in Shuangshi Tonglin Capsules are as follows: the mass ratios of Cortex Phellodendri Amurensis, Salvia miltiorrhiza, Rhizoma Dioscoreae Hypoglaucae, Patrinia scabiosaefolia, Plantago asiatica, Talcum, Poria, Atractylodes lancea, Acorus tatarinowii, and Indigo Naturalis are 16:32:32:32:32:19:16:16:16:5 respectively.

2. The method for increasing the transfer rate of berberine hydrochloride in Shuangshi Tonglin Capsules according to claim 1, wherein The Cortex Phellodendri Amurensis is decocted three times, and after each decoction reaches boiling, circulation is carried out once every 30 minutes, and each circulation lasts for 10 minutes.

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