A preparation method of Xuesaitong dripping pills

Abstract

The present invention provides a preparation method of Xuesaitong dripping pills, comprising the following steps: S1. heating the dripping pill matrix at a temperature of 80 to 95° C. to melt, and maintaining the temperature; S2. adding Panax notoginseng total saponins and ethyl cellulose to ethanol, and stirring until dissolved, to prepare a Panax notoginseng total saponins dispersion solution; S3. adding the molten matrix obtained in step S1 to the liquid storage tank of a dripping pill machine, injecting the Panax notoginseng total saponins dispersion solution from the dropper of the dripping pill machine during the dripping process, and dripping it into the coolant at a speed of 40 to 60 drops per minute, condensing to form dripping pills; S4. collecting the dripping pills after the dripping is completed, vibrating and sieving, air-drying, and packaging. According to the preparation method of the present invention, the molten matrix and the Panax notoginseng total saponins dispersion solution are mixed for a short time and then immediately dripped into the coolant for dripping pills, avoiding the molten matrix and the Panax notoginseng total saponins from contacting and mixing for a long time, and reducing the influence of high temperature on the Panax notoginseng total saponins as much as possible.

Description

Technical Field

[0001] The invention relates to the technical field of medicines, and in particular to a preparation method of Xuesaitong dropping pills. Background Art

[0002] Cardiovascular and cerebrovascular diseases are very common diseases in clinic, and in recent years, the incidence and mortality of cardiovascular and cerebrovascular diseases have shown an upward trend. Effective prevention and treatment of cardiovascular and cerebrovascular diseases has become an important topic for medical workers.

[0003] Panax notoginseng is a perennial herbaceous plant of the Araliaceae family, also known as Tianqi, Shensanqi, etc., and is of the same family and genus as ginseng. The chemical components extracted and studied from Panax notoginseng include saponins, notoginseng, polysaccharides, amino acids, flavonoids, phytosterols, fatty acids, volatile oils, aliphatic acetylene compounds and trace elements. Panax notoginseng total saponin is the main saponin component in Panax notoginseng. Pharmacological studies have shown that Panax notoginseng total saponin has the effects of promoting blood circulation and removing blood stasis, dredge meridians and activate collaterals, inhibit platelet aggregation and increase cardiovascular and cerebral blood flow, and can play an active therapeutic role in cardiovascular and cerebrovascular diseases. At present, pharmaceutical preparations with Panax notoginseng total saponin as the main ingredient include Xuesaitong tablets, Xuesaitong dripping pills, etc. Among them, Xuesaitong dripping pills have the advantages of fast onset, simple preparation process, and convenient oral administration, and have become a current research hotspot.

[0004] During the preparation of Xuesaitong pills, the process of making pills is adopted in which Panax notoginseng total saponins and molten pill matrix are kept in contact and stirred for a long time. If Panax notoginseng total saponins are exposed to high temperature conditions for a long time, it will affect the biological activity and thus affect the efficacy. Summary of the invention

[0005] In view of this, the present invention aims to provide a method for preparing Xuesaitong dropping pills to solve the problem that the biological activity of the active ingredient Panax notoginseng total saponins is affected during the preparation of Xuesaitong dropping pills.

[0006] To achieve the above object, the technical solution of the present invention is achieved as follows:

[0007] A method for preparing Xuesaitong dripping pills comprises the following steps:

[0008] S1. The pellet matrix is ​​heated at 80-95°C until it melts and maintained at this temperature;

[0009] S2. Adding Panax notoginseng total saponins and ethyl cellulose to ethanol and stirring until dissolved to prepare a Panax notoginseng total saponins dispersion solution;

[0010] S3. The molten matrix obtained in step S1 is added to the liquid storage tank of the pill machine, and the Panax notoginseng total saponin dispersion solution is injected from the dropper of the pill machine during the dropping process, and is added dropwise to the coolant at a rate of 40 to 60 drops per minute to condense and form pills;

[0011] S4. After the dripping process is completed, the dripping pills are collected, sieved, air-dried, and packaged.

[0012] Furthermore, the mass ratio of the Panax notoginseng total saponins to the matrix is ​​1:3-8.

[0013] Furthermore, in step S2, the mass ratio of the notoginseng total saponins, ethyl cellulose and ethanol is 1:0.05-0.1:3-5.

[0014] Furthermore, in step S2, notoginseng total saponins and ethyl cellulose are added to ethanol, and then Span 80 is added and stirred until dissolved to prepare a notoginseng total saponins dispersed solution.

[0015] Furthermore, the mass ratio of the Panax notoginseng total saponins to Span 80 is 1:0.2-0.5.

[0016] Furthermore, the matrix is ​​selected from at least one of polyethylene glycol 4000 and polyethylene glycol 6000.

[0017] Furthermore, the cooling liquid is selected from dimethyl silicone oil, and the temperature is 3 to 15°C.

[0018] Furthermore, during the process of dripping into the coolant, the dripper of the pill machine and the liquid level of the coolant are maintained at a height of 3 to 8 cm, and the diameter of the dripper is 2 to 4 mm.

[0019] Compared with the prior art, the preparation method of the Xuesaitong dripping pills described in the present invention has the following advantages:

[0020] (1) The molten matrix is ​​transported to the liquid storage tank, and the Panax notoginseng total saponin dispersion solution is injected from the dropper of the pill dropping machine during the dropping process. After the molten matrix and the Panax notoginseng total saponin dispersion solution are mixed for a short time, they are immediately dropped into the cooling liquid for pill dropping to avoid long-term contact and mixing between the molten matrix and Panax notoginseng total saponins, thereby minimizing the impact of high temperature on Panax notoginseng total saponins.

[0021] (2) The use of ethyl cellulose can accelerate the dispersion effect of Panax notoginseng total saponins, so that the obtained Panax notoginseng total saponins dispersion solution can be quickly dispersed after contacting with the molten matrix to avoid uneven distribution.

[0022] (3) Use Span 80 to reduce the defoaming time after stirring and improve preparation efficiency. DETAILED DESCRIPTION

[0023] The present invention will be further described below in conjunction with specific embodiments. It should be noted that the data in the following experimental examples are obtained by the inventor through a large number of experiments. Due to space limitations, only a part of them is shown in the specification, and those of ordinary skill in the art can understand and implement the present invention under these data. These embodiments are only used to illustrate the present invention and are not intended to limit the scope of the present invention. In addition, it should be understood that after reading the content of the present invention, those skilled in the art can make various changes or modifications to the present invention, and these changes or modifications also fall within the scope protected by the present application.

[0024] Example 1

[0025] 8 parts of polyethylene glycol 6000 were heated to melt at 80°C and maintained at this temperature. 1 part of notoginseng total saponins and 0.1 part of ethyl cellulose were added to 4 parts of ethanol and stirred until dissolved to prepare a notoginseng total saponins dispersion solution.

[0026] The molten matrix is ​​added to the liquid storage tank of the pill machine. During the dripping process, the prepared Panax notoginseng total saponin dispersion solution is injected from the dropper of the pill machine, and dripped into the dimethyl silicone oil coolant at a temperature of 3°C at a rate of 40 to 60 drops per minute to condense and form pills. The dropper of the pill machine and the liquid level of the coolant are maintained at a height of 3 cm, and the diameter of the dropper is 2 to 4 mm. After the dripping is completed, the pills are collected, vibrated, air-dried, and packaged to obtain the Xuesaitong pills.

[0027] Example 2

[0028] 8 parts of polyethylene glycol 6000 were heated to melt at 80°C and maintained at this temperature. 1 part of notoginseng total saponin and 0.1 part of ethyl cellulose were added to 4 parts of ethanol, and then 0.2 parts of Span 80 were added and stirred until dissolved to prepare a notoginseng total saponin dispersion solution.

[0029] The molten matrix is ​​added to the liquid storage tank of the pill machine. During the dripping process, the prepared Panax notoginseng total saponin dispersion solution is injected from the dropper of the pill machine, and dripped into the dimethyl silicone oil coolant at a temperature of 3°C at a rate of 40 to 60 drops per minute to condense and form pills. The dropper of the pill machine and the liquid level of the coolant are maintained at a height of 3 cm, and the diameter of the dropper is 2 to 4 mm. After the dripping is completed, the pills are collected, vibrated, air-dried, and packaged to obtain the Xuesaitong pills.

[0030] Example 3

[0031] 3 parts of polyethylene glycol 4000 were heated to 85°C until melted and maintained at this temperature. 1 part of Panax notoginseng total saponins and 0.08 parts of ethyl cellulose were added to 3 parts of ethanol, and then 0.5 parts of Span 80 were added and stirred until dissolved to prepare a Panax notoginseng total saponins dispersion solution.

[0032] The molten matrix is ​​added to the liquid storage tank of the pill machine. During the dripping process, the prepared Panax notoginseng total saponin dispersion solution is injected from the dropper of the pill machine, and dripped into the dimethyl silicone oil coolant at a temperature of 10°C at a rate of 40 to 60 drops per minute to condense and form pills. The dropper of the pill machine and the liquid level of the coolant are maintained at a height of 5 cm, and the diameter of the dropper is 2 to 4 mm. After the dripping is completed, the pills are collected, vibrated, air-dried, and packaged to obtain the Xuesaitong pills.

[0033] Example 4

[0034] 8 parts of polyethylene glycol 6000 were heated to melt at 80°C, 0.03 parts of sucrose were added, and the temperature was maintained. 1 part of notoginseng total saponin and 0.1 parts of ethyl cellulose were added to 4 parts of ethanol, and then 0.2 parts of Span 80 were added and stirred until dissolved to prepare a notoginseng total saponin dispersion solution.

[0035] The molten matrix is ​​added to the liquid storage tank of the pill machine. During the dripping process, the prepared Panax notoginseng total saponin dispersion solution is injected from the dropper of the pill machine, and dripped into the dimethyl silicone oil coolant at a temperature of 3°C at a rate of 40 to 60 drops per minute to condense and form pills. The dropper of the pill machine and the liquid level of the coolant are maintained at a height of 3 cm, and the diameter of the dropper is 2 to 4 mm. After the dripping is completed, the pills are collected, vibrated, air-dried, and packaged to obtain the Xuesaitong pills.

[0036] Example 5

[0037] 5 parts of polyethylene glycol 4000 were heated to melt at 95°C, 0.02 parts of xylitol were added, and the temperature was maintained. 1 part of notoginseng total saponin and 0.05 parts of ethyl cellulose were added to 5 parts of ethanol, and then 0.3 parts of Span 80 were added and stirred until dissolved to prepare a notoginseng total saponin dispersion solution.

[0038] The molten matrix is ​​added to the liquid storage tank of the pill machine. During the dripping process, the prepared Panax notoginseng total saponin dispersion solution is injected from the dropper of the pill machine, and dripped into the dimethyl silicone oil coolant at a temperature of 15°C at a rate of 40 to 60 drops per minute to condense and form pills. The dropper of the pill machine and the liquid level of the coolant are maintained at a height of 5 cm, and the diameter of the dropper is 2 to 4 mm. After the dripping is completed, the pills are collected, vibrated, air-dried, and packaged to obtain the Xuesaitong pills.

[0039] Example 6

[0040] 3 parts of polyethylene glycol 4000 and 4 parts of polyethylene glycol 6000 were heated to melt at 90°C, 0.05 parts of xylitol were added, and the temperature was maintained. 1 part of notoginseng total saponin and 0.1 parts of ethyl cellulose were added to 4.5 parts of ethanol, and then 0.2 parts of Span 80 were added and stirred until dissolved to prepare a notoginseng total saponin dispersion solution.

[0041] The molten matrix is ​​added to the liquid storage tank of the pill machine. During the dripping process, the prepared Panax notoginseng total saponin dispersion solution is injected from the dropper of the pill machine, and dripped into the dimethyl silicone oil coolant at a temperature of 10°C at a rate of 40 to 60 drops per minute to condense and form pills. The dropper of the pill machine and the liquid level of the coolant are maintained at a height of 8 cm, and the diameter of the dropper is 2 to 4 mm. After the dripping is completed, the pills are collected, vibrated, air-dried, and packaged to obtain the Xuesaitong pills.

[0042] Example 7

[0043] 4 parts of polyethylene glycol 6000 and 4 parts of polyethylene glycol 4000 were heated to melt at 80°C, 0.03 parts of sucrose were added, and the temperature was maintained. 1 part of notoginseng total saponin and 0.1 parts of ethyl cellulose were added to 4 parts of ethanol, and then 0.2 parts of Span 80 were added and stirred until dissolved to prepare a notoginseng total saponin dispersion solution.

[0044] The molten matrix is ​​added to the liquid storage tank of the pill machine. During the dripping process, the prepared Panax notoginseng total saponin dispersion solution is injected from the dropper of the pill machine, and dripped into the dimethyl silicone oil coolant at a temperature of 5°C at a rate of 40 to 60 drops per minute to condense and form pills. The dropper of the pill machine and the liquid level of the coolant are maintained at a height of 3 cm, and the diameter of the dropper is 2 to 4 mm. After the dripping is completed, the pills are collected, vibrated, air-dried, and packaged to obtain the Xuesaitong pills.

[0045] Comparative Example 1

[0046] Put 8 parts of polyethylene glycol 6000 into the liquid storage tank of the pill machine, heat it at 80℃ until it melts, add 1 part of Panax notoginseng total saponins into the liquid storage tank, continue to heat at 80℃ until the Panax notoginseng total saponins are completely dissolved, and then drip it into the dimethyl silicone oil coolant at a temperature of 3℃ at a rate of 40 to 60 drops per minute to condense to form pills. The dripper of the pill machine and the liquid level of the coolant are maintained at a height of 3cm, and the diameter of the dripper is 2 to 4mm. After the dripping is completed, collect the pills, vibrate, air-dry, and package them to obtain Xuesaitong pills.

[0047] Comparative Example 2

[0048] The components, dosages and preparation method of Comparative Example 2 are the same as those of Example 2, except that ethyl cellulose is not added.

[0049] Comparative Example 3

[0050] Xuesaitong dripping pills are prepared by the method in CN1255108C.

[0051] Comparative Example 4

[0052] Commercially available Xuesaitong pills.

[0053] The content of effective ingredients in the Xuesaitong dripping pills prepared in Examples 1-2 and Comparative Examples 1-2 was determined. For specific determination methods, refer to: Lou Guiqin, He Baoling, Jia Zheng. Study on production process and quality standard of Xuesaitong dripping pills [J]. Chinese Medicinal Materials, 2010(8):4. DOI:CNKI:SUN:ZYCA.0.2010-08-045. Notoginsenoside R1, Ginsenoside R g1 and ginsenoside R b1 The content of was determined, and the specific results are shown in Table 1.

[0054] Table 1

[0055]

[0056]

[0057] The results measured in Table 1 are the content detection values ​​of different batches. The content determination results of different batches of comparative example 2 pills are quite different. This shows that without adding dispersant ethyl cellulose, relying solely on the short-time mixing of Panax notoginseng total saponins and the matrix is ​​not conducive to dispersibility.

[0058] It can be seen from Table 1 that the effective ingredients of the Xuesaitong dripping pills of Examples 1 and 2 are higher than those of Comparative Example 1. In Comparative Example 1, which adopts the conventional preparation method of the prior art Xuesaitong dripping pills, the molten matrix and Panax notoginseng saponins will be in contact and mixed for a long time, and the high temperature will affect the biological activity of Panax notoginseng saponins, reduce the content of the effective ingredients, and thus affect the efficacy. In the preparation process of the Xuesaitong dripping pills of Examples 1 and 2, the matrix heated to a molten state is first transported to the liquid storage tank of the dripping pill machine, and then the Panax notoginseng saponins dispersion solution is injected from the dropper of the dripping pill machine during the dropping process. After the molten matrix and the Panax notoginseng saponins dispersion solution are mixed for a short time, they are immediately dripped into the cooling liquid for dripping pills, so as to minimize the influence of high temperature on Panax notoginseng saponins.

[0059] However, since the molten matrix and the Panax notoginseng total saponin dispersion solution are mixed in a short time, it will make it difficult to disperse the Panax notoginseng total saponins evenly. Therefore, the present invention further adds ethyl cellulose. The use of ethyl cellulose can accelerate the dispersion effect of Panax notoginseng total saponins, so that the obtained Panax notoginseng total saponin dispersion solution can be quickly dispersed after contacting the molten matrix to avoid uneven distribution.

[0060] The defoaming time, roundness and dissolution rate of the Xuesaitong dropping pills of Examples 1 to 7 and Comparative Examples 3 to 4 were tested.

[0061] The defoaming time of Examples 1 to 7 refers to the preparation of the Panax notoginseng total saponin dispersion solution, which is measured from the time when stirring is stopped to the time when the foam in the Panax notoginseng total saponin dispersion solution completely disappears. For Comparative Example 3, defoaming is produced after PEG6000 is heated and melted in a 90-100°C water bath, and then the Panax notoginseng total saponin fine powder is added and mixed evenly. The defoaming time of Comparative Example 3 is measured from the time when stirring is stopped to the time when the foam in the mixture completely disappears after the Panax notoginseng total saponin fine powder is added and mixed evenly. Comparative Example 4 is a commercially available Xuesaitong dripping pill, and the defoaming time is not calculated. In Table 2, the stirring speed of each group is kept the same.

[0062] The roundness of the pills was measured by the ratio of the shortest diameter to the longest diameter of the pills. A ratio of 0.95 or above was 5 points, 0.9 to 0.95 was 4 points, 0.85 to 0.9 was 3 points, 0.8 to 0.85 was 2 points, and 0.8 or below was 1 point.

[0063] Dissolution time determination method: Refer to the standard under 0108 Pills in the 2020 edition of the "Chinese Pharmacopoeia" (Part 4) for determination. The dissolution time limit pills should be completely dissolved within 30 minutes.

[0064] Table 2

[0065] Defoaming time (min) Roundness of pills Dissolution time (min) Example 1 58 3 7.3 Example 2 41 3 7.3 Example 3 34 3 8.1 Example 4 43 5 6.8 Example 5 36 5 8.0 Example 6 40 5 6.5 Example 7 40 5 6.3 Comparative Example 3 83 4 9.9 Comparative Example 4 / 3 13.0

[0066] Regarding the preparation of the Panax notoginseng total saponin dispersion solution, it is usually necessary to stir the Panax notoginseng total saponin to quickly dissolve in ethanol. A large amount of foam will be generated during the stirring process, and it is usually necessary to stand and wait for defoaming to avoid the adverse effect of foam on the morphology of the pills. For industrial large-scale production, a long standing time will greatly waste time, which is not conducive to the improvement of pharmaceutical efficiency. When preparing the Xuesaitong pills in Example 1, the defoaming time is 58min, and a long waiting time is required. Therefore, the applicant further studied this and found that the preparation of the Panax notoginseng total saponin dispersion solution can shorten the defoaming time to 34-43min by adding Span 80, saving waiting time and greatly improving the production efficiency of the Xuesaitong pills.

[0067] Good roundness of the pills is conducive to improving the appearance and overall quality of the Xuesaitong pills. In the present invention, in order to improve the dispersibility of Panax notoginseng total saponins in the molten matrix, it is necessary to first dissolve Panax notoginseng total saponins in ethanol. The material will be thinner when the pills are dripped, and it is easy to cause the dripping speed to be difficult to control during dripping, resulting in the shrinkage of the pills not being round and the pills being of different sizes. For example, the roundness score of the Xuesaitong pills of Examples 1 to 3 is only 3 points. The inventors found that adding any one of sucrose, mannitol, and xylitol to the molten matrix, and the mass ratio of Panax notoginseng total saponins to the sugar is 1:0.02 to 0.05, can improve the roundness of the pills, and the prepared pills are more uniform in size, which improves the yield rate. For example, the roundness score of the Xuesaitong pills of Examples 4 to 7 reached 5 points. It is speculated that this may be because both the Panax notoginseng total saponins and the above-mentioned sugars contain a large number of hydroxyl groups. After the Panax notoginseng total saponins dispersion solution comes into contact with the matrix containing sugar, there is a strong attraction between the Panax notoginseng total saponins and the sugar, which increases the surface tension of the Panax notoginseng total saponins dispersion solution and shrinks better when it is dropped into pills.

[0068] In addition, the Xuesaitong pills prepared by the method of the present invention have a shorter dissolution time. The Xuesaitong pills prepared by the method of the present invention have better roundness and dissolution time, and can shorten the waiting time and improve the efficiency during large-scale production, and can protect the effective components of Panax notoginseng total saponins from being affected by high temperature.

[0069] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing Xuesaitong dripping pills, characterized in that: The steps include: S1. The pellet matrix is ​​heated at 80 to 95°C until it is melted, and any one of sucrose, mannitol, and xylitol is added to the molten matrix, and this temperature is maintained; S2. Adding Panax notoginseng total saponins and ethyl cellulose to ethanol and stirring until dissolved to prepare a Panax notoginseng total saponins dispersion solution; S3. The molten matrix obtained in step S1 is added to the liquid storage tank of the pill machine, and the Panax notoginseng total saponin dispersion solution is injected from the dropper of the pill machine during the dropping process, and is added dropwise to the coolant at a rate of 40 to 60 drops per minute to condense and form pills; S4. After the dripping process is completed, the dripping pills are collected, sieved, air-dried, and packaged.

2. The method for preparing the Xuesaitong dripping pills according to claim 1, characterized in that: The mass ratio of the total saponins of Panax notoginseng to the matrix is ​​1:3-8.

3. The method for preparing Xuesaitong dripping pills according to claim 1, characterized in that: In step S2, the mass ratio of the Panax notoginseng total saponins, ethyl cellulose and ethanol is 1:0.05-0.1:3-5.

4. The method for preparing Xuesaitong dripping pills according to claim 1, characterized in that: In step S2, Panax notoginseng total saponins and ethyl cellulose are added to ethanol, and then Span 80 is added and stirred until dissolved to prepare a Panax notoginseng total saponins dispersed solution.

5. The method for preparing Xuesaitong dripping pills according to claim 4, characterized in that: The mass ratio of the total saponins of Panax notoginseng to Span 80 is 1:0.2-0.

5.

6. The method for preparing Xuesaitong dripping pills according to claim 1, characterized in that: The matrix is ​​selected from at least one of polyethylene glycol 4000 and polyethylene glycol 6000.

7. The method for preparing Xuesaitong dripping pills according to claim 1, characterized in that: The cooling liquid is selected from dimethyl silicone oil, and the temperature is 3-15°C.

8. The method for preparing Xuesaitong dripping pills according to claim 1, characterized in that: During the process of dripping into the coolant, the dripping head of the pill machine and the liquid level of the coolant are maintained at a height of 3 to 8 cm, and the diameter of the dripping head is 2 to 4 mm.

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