LU503014B1 - BRAIN-TONIFYING GRANULES AND PREPARATION METHOD THEREOF - Google Patents
BRAIN-TONIFYING GRANULES AND PREPARATION METHOD THEREOF Download PDFInfo
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- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
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Abstract
Disclosed are brain-tonifying granules and a preparation method thereof. The brain-tonifying granules are prepared from processed Rhizoma polygonati, processed Rhizoma polygonati odorati, Semen cassiae, Rhizoma chuanxiong and pharmaceutic auxiliary materials. The preparation process mainly includes: pretreatment of medicinal materials, extraction, filtration, concentration, alcohol precipitation, drying, granulation and the like. The brain-tonifying granules prepared by the preparation method of the present invention have the functions of nourishing the brain and calming the nerves, regulating five internal organs and harmonizing qi and blood, and also have the advantages of convenient use, convenient storage, convenient transportation and the like.Disclosed are brain-tonifying granules and a preparation method thereof. The brain-tonifying granules are prepared from processed Rhizoma polygonati, processed Rhizoma polygonati odorati, Semen cassiae, Rhizoma chuanxiong and pharmaceutical auxiliary materials. The preparation process mainly includes: pretreatment of medicinal materials, extraction, filtration, concentration, alcohol precipitation, drying, granulation and the like. The brain-tonifying granules prepared by the preparation method of the present invention have the functions of nourishing the brain and calming the nerves, regulating five internal organs and harmonizing qi and blood, and also have the advantages of convenient use, convenient storage, convenient transportation and the like.
Description
BL-5573BL-5573
BRAIN-TONIFYING GRANULES AND PREPARATION METHOD THEREOF | L/*0501$BRAIN-TONIFYING GRANULES AND PREPARATION METHOD THEREOF | L/*0501$
[01] The present invention belongs to the technical field of preparation of drugs for external use, and particularly relates to brain-tonifying granules and a preparation method thereof.[01] The present invention belongs to the technical field of preparation of drugs for external use, and particularly relates to brain-tonifying granules and a preparation method thereof.
[02] With the development of China’s aging population, the incidence of insufficient brain power has been rising year by year, and the symptoms include insomnia, memory decline and the like. The disease has affected patients’ physical health and daily life, and has become an increasingly serious social problem.[02] With the development of China's aging population, the incidence of insufficient brain power has been rising year by year, and the symptoms include insomnia, memory decline and the like. The disease has affected patients' physical health and daily life, and has become an increasingly serious social problem.
[03] The experienced prescription of “Brain-tonifying Decoction” originated from[03] The experienced prescription of “Brain-tonifying Decoction” originated from
Wei Changchun, a prestigious doctor of traditional Chinese medicine, is composed of four medicinal materials: processed Rhizoma polygonati, processed Rhizoma polygonati odorati, Semen cassiae and Rhizoma chuanxiong. The prescription has the functions of nourishing the brain and calming the nerves, regulating five internal organs and harmonizing qi and blood, and has been widely applied in clinical practice. Following the idea of Monarch, Minister, Assistant and Guide in traditional Chinese medicine, the prescription takes Rhizoma polygonati and Rhizoma polygonati odorati as monarch, andWei Changchun, a prestigious doctor of traditional Chinese medicine, is composed of four medicinal materials: processed Rhizoma polygonati, processed Rhizoma polygonati odorati, Semen cassiae and Rhizoma chuanxiong. The prescription has the functions of nourishing the brain and calming the nerves, regulating five internal organs and harmonizing qi and blood, and has been widely applied in clinical practice. Following the idea of Monarch, Minister, Assistant and Guide in traditional Chinese medicine, the prescription takes Rhizoma polygonati and Rhizoma polygonati odorati as monarch, and
Semen cassiae and Rhizoma chuanxiong as minister. The main active components ofSemen cassiae and Rhizoma chuanxiong as minister. The main active components of
Rhizoma polygonati are polygahatous polysaccharides, saponins, flavonoids, etc. With extremely extensive pharmacological effects, the Rhizoma polygonati has the anti-aging, memory improvement, immunity enhancement and immunity functions. The Rhizoma polygonati odorati is sweet, mild in nature and slightly cold, has the functions of nourishing yin and moistening dryness, and engendering liquid and allaying thirst, and has the pharmacological effects of blood glucose lowering, immune regulation, anti-tumor, anti-oxidation, skin aging delaying, etc. The Rhizoma polygonati has the effect of regulating blood lipids. Moreover, the polygonatum polysaccharides and steroid saponins of the Rhizoma polygonati odorati are the main active components of playing pharmacological effects. The Rhizoma polygonati and Rhizoma polygonati odorati are used in the prescription, and the health function of such two medicines is similar. The modern pharmacological studies show that both of them have the functions of lowering blood glucose and regulating immunity. The Semen cassiae has the pharmacological effects of clearing liver and improving vision, regulating blood pressure and lowering blood lipids, relaxing bowel, etc. Studies show that the Semen cassiae not only has the main components of anthraquinones, but also has the volatile components and polysaccharide. The Rhizoma chuanxiong has the anti-inflammatory, anti-thrombosis, anti-asthma and other pharmacological effects, with the main components of volatile oil, alkaloid and polysaccharide.Rhizoma polygonati are polygahatous polysaccharides, saponins, flavonoids, etc. With extremely extensive pharmacological effects, the Rhizoma polygonati has the anti-aging, memory improvement, immunity enhancement and immunity functions. The Rhizoma polygonati odorati is sweet, mild in nature and slightly cold, has the functions of nourishing yin and moistening dryness, and engendering liquid and allaying thirst, and has the pharmacological effects of blood glucose lowering, immune regulation, anti-tumor, anti- oxidation, skin aging delay, etc. The Rhizoma polygonati has the effect of regulating blood lipids. Moreover, the polygonatum polysaccharides and steroid saponins of the Rhizoma polygonati odorati are the main active components of playing pharmacological effects. The Rhizoma polygonati and Rhizoma polygonati odorati are used in the prescription, and the health function of such two medicines is similar. The modern pharmacological studies show that both of them have the functions of lowering blood glucose and regulating immunity. The Semen cassiae has the pharmacological effects of clearing liver and improving vision, regulating blood pressure and lowering blood lipids, relaxing bowel, etc. Studies show that the Semen cassiae not only has the main components of anthraquinones, but also has the volatile components and polysaccharide. The Rhizoma chuanxiong has the anti-inflammatory, anti-thrombosis, anti-asthma and other pharmacological effects, with the main components of volatile oil, alkaloid and polysaccharide.
[04] The original prescription is the decoction prepared by the method that the medicinal materials are decocted or immersed in water, and the residue is discarded.[04] The original prescription is the decoction prepared by the method that the medicinal materials are decocted or immersed in water, and the residue is discarded.
The advantage of decoction lies in flexible components, in which the medicines can be increased or decreased according to the patient’s needs. The decoction takes effect 1The advantage of decoction lies in flexible components, in which the medicines can be increased or decreased according to the patient's needs. The decoction takes effect 1
BL-5573 quickly and is easy to absorb after oral administration. However, the disadvantage lies LU503014 in long dectocting time, inconvenient preservation, inconvenient carrying and inflexible drinking. In order to allow traditional Chinese medicine preparations to satisfy more needs, granules are derived. The granules retain the characteristics of quick response and easy absorption of traditional decoction, and have the advantages of short preparation time without decoction, precise dose, easy carrying, uniform specifications, consistent standards and the like.BL-5573 quickly and is easy to absorb after oral administration. However, the disadvantage lies LU503014 in long dectocting time, inconvenient preservation, inconvenient carrying and inflexible drinking. In order to allow traditional Chinese medicine preparations to satisfy more needs, granules are derived. The granules retain the characteristics of quick response and easy absorption of traditional decoction, and have the advantages of short preparation time without decoction, precise dose, easy carrying, uniform specifications, consistent standards and the like.
[05] The prescription is specific to the elderly people with insufficient brain power.[05] The prescription is specific to the elderly people with insufficient brain power.
With the development of China’s aging population, the incidence of insufficient brain power has been rising year by year, and the disease has become a hot social problem.With the development of China's aging population, the incidence of insufficient brain power has been rising year by year, and the disease has become a hot social problem.
The prescription has a wide audience range and a huge market demand as the elderly people with insufficient brain power are increasing. Moreover, the raw materials of the prescription are readily available and the preparation process is simple. The granules of the present invention can meet the needs of patients to the maximum extent while ensuring that the insufficient brain power can be effectively improved; moreover, the granules fill the market vacancy, so that economic benefits are considerable.The prescription has a wide audience range and a huge market demand as the elderly people with insufficient brain power are increasing. Moreover, the raw materials of the prescription are readily available and the preparation process is simple. The granules of the present invention can meet the needs of patients to the maximum extent while ensuring that the insufficient brain power can be effectively improved; moreover, the granules fill the market vacancy, so that economic benefits are considerable.
[06] To solve the problems in the prior art, one objective of the present invention is to provide brain-tonifying granules.[06] To solve the problems in the prior art, one objective of the present invention is to provide brain-tonifying granules.
[07] The present invention is realized by the following technical solutions:[07] The present invention is realized by the following technical solutions:
[08] Brain-tonifying granules include an aqueous extract of plants and pharmaceutic auxiliary materials, wherein the aqueous extract of plants includes the following parts by weight of components: 25-35 parts of processed Rhizoma polygonati, 25-30 parts of processed Rhizoma polygonati odorati, 5-15 parts of Semen cassiae and 1-5 parts of[08] Brain-tonifying granules include an aqueous extract of plants and pharmaceutical auxiliary materials, wherein the aqueous extract of plants includes the following parts by weight of components: 25-35 parts of processed Rhizoma polygonati, 25-30 parts of processed Rhizoma polygonati odorati, 5-15 parts of Semen cassiae and 1-5 parts of
Rhizoma chuanxiong, the pharmaceutic auxiliary materials include a filling agent, a wetting agent and a binding agent, wherein the filling agent is one or more of sucrose, starch, dextrin, lactose, mannitol and sodium alginate; the filling agent is 30 wt%-60 wt%, and the binding agent is 0 wt%-5 wt%.Rhizoma chuanxiong, the pharmaceutical auxiliary materials include a filling agent, a wetting agent and a binding agent, wherein the filling agent is one or more of sucrose, starch, dextrin, lactose, mannitol and sodium alginate; the filling agent is 30 wt%-60 wt%, and the binding agent is 0 wt%-5 wt%.
[09] Preferably, the aqueous extract of plants includes the following parts by weight of components: 30 parts of processed Rhizoma polygonati, 30 parts of processed[09] Furthermore, the aqueous extract of plants includes the following parts by weight of components: 30 parts of processed Rhizoma polygonati, 30 parts of processed
Rhizoma polygonati odorati, 9 parts of Semen cassiae and 3 parts of Rhizoma chuanxiong.Rhizoma polygonati odorati, 9 parts of Semen cassiae and 3 parts of Rhizoma chuanxiong.
[10] Preferably, the wetting agent is 1 wt%-10 wt%; the wetting agent is 80%-95% ethanol (volume content) or water.[10] However, the wetting agent is 1 wt%-10 wt%; the wetting agent is 80%-95% ethanol (volume content) or water.
[11] Preferably, the binding agent is one of povidone, polyethylene glycol and hydroxy propyl cellulose.[11] However, the binding agent is one of povidone, polyethylene glycol and hydroxy propyl cellulose.
[12] Another objective of the present invention is to provide a method for preparing brain-tonifying granules, including the following steps:[12] Another objective of the present invention is to provide a method for preparing brain-tonifying granules, including the following steps:
[13] 1) weighing processed Rhizoma polygonati, processed Rhizoma polygonati odorati, Semen cassiae and Rhizoma chuanxiong respectively according to formula ratios, and mixing and crushing such raw materials to obtain a medicinal material mixture;[13] 1) weighing processed Rhizoma polygonati, processed Rhizoma polygonati odorati, Semen cassiae and Rhizoma chuanxiong respectively according to formula ratios, and mixing and crushing such raw materials to obtain a medicinal material mixture;
[14] 2) immersing the medicinal material mixture prepared in step 1) into a 6-fold to 2[14] 2) immersing the medicinal material mixture prepared in step 1) into a 6-fold to 2
BL-5573 10-fold amount (based on a mass of the medicinal material mixture) of purified water LU503014 for 1h, successively boiling with fast fire and decocting with slow fire the medicinal material mixture for 1h, and filtrating the medicinal material mixture; adding a 6-fold to 10-fold amount of purified water and boiling with fast fire and decocting with slow fire the medicinal material mixture for 1h again, combining the filtrate, and concentrating the combined filtrate to 1/3-2/3 of the original amount to obtain an aqueous extract concentrate;BL-5573 10-fold amount (based on a mass of the medicinal material mixture) of purified water LU503014 for 1h, successively boiling with fast fire and decocting with slow fire the medicinal material mixture for 1h, and filtrating the medicinal material mixture; adding a 6-fold to 10-fold amount of purified water and boiling with fast fire and decocting with slow fire the medicinal material mixture for 1h again, combining the filtrate, and concentrating the combined filtrate to 1/3-2/3 of the original amount to obtain an aqueous extract concentrate;
[15] 3) adding ethanol to the aqueous extract concentrate until the ethanol concentration reaches 60-80%(v/v), and placing the mixed solution in a refrigerator at 4°C for 24 h; mixing evenly and centrifugating the mixed solution, taking the supernatant and concentrating to 1/3-2/3 of the original amount, drying the concentrate under reduced pressure and crushing the dried productto obtain dry paste powder;[15] 3) adding ethanol to the aqueous extract concentrate until the ethanol concentration reaches 60-80%(v/v), and placing the mixed solution in a refrigerator at 4°C for 24 h; mixing evenly and centrifugating the mixed solution, taking the supernatant and concentrating to 1/3-2/3 of the original amount, drying the concentrate under reduced pressure and crushing the dried product to obtain dry paste powder;
[16] 4) turning on a high-speed stirring granulator, setting parameters, adding the dry paste powder and a filling agent to a mixing tank, and turning on an agitator blade for dry mixing; adding a binding agent and a wetting agent evenly in a wet mixing process, and turning on a cutter knife; upon completion of granulation, discharging granules and drying the granules at 60°C for 10-40 min; and[16] 4) turning on a high-speed stirring granulator, setting parameters, adding the dry paste powder and a filling agent to a mixing tank, and turning on an agitator blade for dry mixing; adding a binding agent and a wetting agent evenly in a wet mixing process, and turning on a cutter knife; upon completion of granulation, discharging granules and drying the granules at 60°C for 10-40 min; and
[17] 5) packaging the granules.[17] 5) packaging the granules.
[18] Preferably, the parameters of the high-speed stirring granulator are as follows: a dry mixing time is 3-5 min, a wet mixing time is 1-10 min, a granulation time is 1-4 min, a dry mixing stirring speed is 400-600 rpm, a wet mixing stirring speed is 400-600 rpm, a granulation stirring speed is 1,000-1,500 rpm, and a cutting speed is 2,000-3,000 rpm.[18] However, the parameters of the high-speed stirring granulator are as follows: a dry mixing time is 3-5 min, a wet mixing time is 1-10 min, a granulation time is 1-4 min, a dry mixing stirring speed is 400-600 rpm, a wet mixing stirring speed is 400-600 rpm, a granulation stirring speed is 1,000-1,500 rpm, and a cutting speed is 2,000-3,000 rpm.
[19] The present invention has the following advantages:[19] The present invention has the following advantages:
[20] The brain-tonifying granules of the present invention are prepared from processed Rhizoma polygonati, processed Rhizoma polygonati odorati, Semen cassiae,[20] The brain-tonifying granules of the present invention are prepared from processed Rhizoma polygonati, processed Rhizoma polygonati odorati, Semen cassiae,
Rhizoma chuanxiong and pharmaceutic auxiliary materials, and the preparation process mainly includes: pretreatment of medicinal materials, extraction, filtration, concentration, alcohol precipitation, drying, granulation and the like. The brain-tonifying granules prepared by the preparation method of the present invention have the functions of nourishing the brain and calming the nerves, regulating five internal organs and harmonizing qi and blood, and also have the advantages of convenient use, convenient storage, convenient transportation and the like.Rhizoma chuanxiong and pharmaceutical auxiliary materials, and the preparation process mainly includes: pretreatment of medicinal materials, extraction, filtration, concentration, alcohol precipitation, drying, granulation and the like. The brain-tonifying granules prepared by the preparation method of the present invention have the functions of nourishing the brain and calming the nerves, regulating five internal organs and harmonizing qi and blood, and also have the advantages of convenient use, convenient storage, convenient transportation and the like.
[21] The brain-tonifying granules have been proved safe and effective by quality inspection and pharmacodynamic experiment. On the basis of full consideration of practicality and effectiveness and previous research, the brain-tonifying granules not only retain the functions of the original prescription, such as nourishing the brain and calming the nerves, regulating five internal organs and harmonizing qi and blood, but also improve the disadvantages of inconvenient use and the like of the original decoction. Therefore, the brain-tonifying granules can not only adapt to market demand, but also have considerable economic benefits.[21] The brain-tonifying granules have been proven safe and effective by quality inspection and pharmacodynamic experiment. On the basis of full consideration of practicality and effectiveness and previous research, the brain-tonifying granules not only retain the functions of the original prescription, such as nourishing the brain and calming the nerves, regulating five internal organs and harmonizing qi and blood, but also improve the disadvantages of inconvenient use and the like of the original decoction. Therefore, the brain-tonifying granules can not only adapt to market demand, but also have considerable economic benefits.
[22] FIG 1: Finished brain-tonifying granules.[22] FIG 1: Finished brain-tonifying granules.
[23] FIG 2: Schematic diagram of water maze. 3[23] FIG 2: Schematic diagram of water maze. 3
BL-5573BL-5573
[24] FIG 3: Experimental result diagram of water maze. LU503014[24] FIG 3: Experimental result diagram of water maze. LU503014
[25] As previously mentioned, in view of the deficiencies in the prior art, the inventor put forward the technical solutions of the present invention through long-term research and extensive practice, mainly based on at least of the followings: 1) The brain-tonifying granules of the present invention include processed Rhizoma polygonati, processed Rhizoma polygonati odorati, Semen cassiae, Rhizoma chuanxiong and pharmaceutic auxiliary materials, and the preparation process mainly includes: pretreatment of medicinal materials, extraction, filtration, concentration, alcohol precipitation, drying, granulation and other processes. The brain-tonifying granules not only retain the functions of the original prescription, such as nourishing the brain and calming the nerves, regulating five internal organs and harmonizing qi and blood, but also improve the disadvantages of inconvenient use and the like of the original decoction. Therefore, the brain-tonifying granules can not only adapt to market demand, but also have considerable economic benefits. 2) The method of the present invention combines the two processes of mixing and granulation together by using a high-speed stirring granulator, which not only saves time but also meets the GMP requirements, reduces cross contamination and greatly improves the efficiency.[25] As previously mentioned, in view of the deficiencies in the prior art, the inventor put forward the technical solutions of the present invention through long-term research and extensive practice, mainly based on at least of the followings: 1) The brain -tonifying granules of the present invention include processed Rhizoma polygonati, processed Rhizoma polygonati odorati, Semen cassiae, Rhizoma chuanxiong and pharmaceutical auxiliary materials, and the preparation process mainly includes: pretreatment of medicinal materials, extraction, filtration, concentration, alcohol precipitation, drying, granulation and other processes. The brain-tonifying granules not only retain the functions of the original prescription, such as nourishing the brain and calming the nerves, regulating five internal organs and harmonizing qi and blood, but also improve the disadvantages of inconvenient use and the like of the original decoction . Therefore, the brain-tonifying granules can not only adapt to market demand, but also have considerable economic benefits. 2) The method of the present invention combines the two processes of mixing and granulation together by using a high-speed stirring granulator, which not only saves time but also meets the GMP requirements, reduces cross contamination and greatly improves the efficiency.
[26] To make the objectives, technical solutions, and advantages of the present invention clearer, the present invention will be further described below in detail in combination with the accompanying drawings and embodiments. It should be understood that specific embodiments described herein are only to explain the present invention but not to limit the present invention. In addition, the technical characteristics in the embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.[26] To make the objectives, technical solutions, and advantages of the present invention clearer, the present invention will be further described below in detail in combination with the accompanying drawings and embodiments. It should be understood that specific embodiments described herein are only to explain the present invention but not to limit the present invention. In addition, the technical characteristics in the embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
[27] In the first aspect, a method for preparing brain-tonifying granules includes the following steps:[27] In the first aspect, a method for preparing brain-tonifying granules includes the following steps:
[28] 1) weighing 25-35 parts of processed Rhizoma polygonati, 25-30 parts of processed Rhizoma polygonati odorati, 5-15 parts of Semen cassiae and 1-5 parts of[28] 1) weighing 25-35 parts of processed Rhizoma polygonati, 25-30 parts of processed Rhizoma polygonati odorati, 5-15 parts of Semen cassiae and 1-5 parts of
Rhizoma chuanxiong, and mixing and crushing such raw materials to obtain a medicinal material mixture;Rhizoma chuanxiong, and mixing and crushing such raw materials to obtain a medicinal material mixture;
[29] 2) immersing the medicinal material mixture prepared in step 1) into a 6-fold to 10-fold amount (based on a mass of the medicinal material mixture) of purified water for 1h, successively boiling with fast fire and decocting with slow fire the medicinal material mixture for 1h, and filtrating the medicinal material mixture; adding a 6-fold to 10-fold amount of purified water and boiling with fast fire and decocting with slow fire the medicinal material mixture for 1h again, combining the filtrate, and concentrating the combined filtrate to 1/3-2/3 of the original amount to obtain an aqueous extract concentrate;[29] 2) immersing the medicinal material mixture prepared in step 1) into a 6-fold to 10-fold amount (based on a mass of the medicinal material mixture) of purified water for 1h, successively boiling with fast fire and decocting with slow fire the medicinal material mixture for 1h, and filtrating the medicinal material mixture; adding a 6-fold to 10-fold amount of purified water and boiling with fast fire and decocting with slow fire the medicinal material mixture for 1h again, combining the filtrate, and concentrating the combined filtrate to 1/3-2/3 of the original amount to obtain an aqueous extract concentrate;
[30] 3) adding ethanol to the aqueous extract concentrate until the ethanol concentration reaches 60-80%, and placing the mixed solution in a refrigerator at 4°C for 24 h; mixing evenly and centrifugating the mixed solution, taking the supernatant and concentrating to 1/3-2/3 of the original amount, drying the concentrate under 4[30] 3) adding ethanol to the aqueous extract concentrate until the ethanol concentration reaches 60-80%, and placing the mixed solution in a refrigerator at 4°C for 24 h; mixing evenly and centrifugating the mixed solution, taking the supernatant and concentrating to 1/3-2/3 of the original amount, drying the concentrate under 4
BL-5573 reduced pressure and crushing the dried product to obtain dry paste powder; LU503014BL-5573 reduced pressure and crushing the dried product to obtain dry paste powder; LU503014
[31] 4) turning on a high-speed stirring granulator, setting parameters, adding the dry paste powder and a filling agent to a mixing tank, and turning on an agitator blade for dry mixing; adding a binding agent and a wetting agent evenly in a wet mixing process, and turning on a cutter knife; upon completion of granulation, discharging granules and drying the granules at 60°C for 10-40 min; wherein the filling agent is one or more of sucrose, starch, dextrin, lactose, mannitol and sodium alginate; the filling agent is 30[31] 4) turning on a high-speed stirring granulator, setting parameters, adding the dry paste powder and a filling agent to a mixing tank, and turning on an agitator blade for dry mixing; adding a binding agent and a wetting agent evenly in a wet mixing process, and turning on a cutter knife; upon completion of granulation, discharging granules and drying the granules at 60°C for 10-40 min; wherein the filling agent is one or more of sucrose, starch, dextrin, lactose, mannitol and sodium alginate; the filling agent is 30
Wt%-60 wt%, and the binding agent is 0 wt%-5 wt%; andWt%-60 wt%, and the binding agent is 0 wt%-5 wt%; and
[32] 5) packaging the granules.[32] 5) packaging the granules.
[33] Preferably, the wetting agent is 1 wt%-10 wt%;[33] However, the wetting agent is 1 wt%-10 wt%;
[34] preferably, the wetting agent is 80%-95% ethanol or water.[34] Preferably, the wetting agent is 80%-95% ethanol or water.
[35] Preferably, the binding agent is one of povidone, polyethylene glycol and hydroxy propyl cellulose.[35] However, the binding agent is one of povidone, polyethylene glycol and hydroxy propyl cellulose.
[36] Preferably, the parameters of the high-speed stirring granulator in step 4) are as follows: a dry mixing time is 3-5 min, a wet mixing time is 1-10 min, a granulation time is 1-4 min, a dry mixing stirring speed is 400-600 rpm, a wet mixing stirring speed is 400-600 rpm, a granulation stirring speed is 1,000-1,500 rpm, and a cutting speed is 2,000-3,000 rpm.[36] However, the parameters of the high-speed stirring granulator in step 4) are as follows: a dry mixing time is 3-5 min, a wet mixing time is 1-10 min, a granulation time is 1-4 min , a dry mixing stirring speed is 400-600 rpm, a wet mixing stirring speed is 400-600 rpm, a granulation stirring speed is 1,000-1,500 rpm, and a cutting speed is 2,000-3,000 rpm.
[37] In the second aspect, brain-tonifying granules include an aqueous extract of plants and pharmaceutic auxiliary materials; wherein the aqueous extract of plants includes the following parts by weight of components: 25-35 parts of processed[37] In the second aspect, brain-tonifying granules include an aqueous extract of plants and pharmaceutical auxiliary materials; wherein the aqueous extract of plants includes the following parts by weight of components: 25-35 parts of processed
Rhizoma polygonati, 25-30 parts of processed Rhizoma polygonati odorati, 5-15 parts ofRhizoma polygonati, 25-30 parts of processed Rhizoma polygonati odorati, 5-15 parts of
Semen cassiae and 1-5 parts of Rhizoma chuanxiong, the pharmaceutic auxiliary materials include a filling agent, a wetting agent and a binding agent.Semen cassiae and 1-5 parts of Rhizoma chuanxiong, the pharmaceutical auxiliary materials include a filling agent, a wetting agent and a binding agent.
[38] The technical solutions of the present invention will be further explained below in combination with some preferred embodiments, but the experimental conditions and set parameters therein should not be regarded as a limitation to the basic technical solutions of the present invention. Moreover, the protection scope of the present invention is not limited to the following embodiments.[38] The technical solutions of the present invention will be further explained below in combination with some preferred embodiments, but the experimental conditions and set parameters therein should not be regarded as a limitation to the basic technical solutions of the present invention. Moreover, the protection scope of the present invention is not limited to the following embodiments.
[39] Example 1[39] Example 1
[40] 30g of processed Rhizoma polygonati, 30g of processed Rhizoma polygonati odorati, 9g of Semen cassiae and 3g of Rhizoma chuanxiong were weighed respectively, and mixed and crushed to obtain a medicinal material mixture. A 10-fold amount (based on a mass of the medicinal material mixture) of purified water was added, and the medicinal material mixture was immersed for 1h, boiled with fast fire and decocted with slow fire for 1h, and filtrated. An 8-fold amount of purified water was added, the medicinal material mixture was immersed for 1h, boiled with fast fire and decocted with slow fire for 1h again. The filtrate was combined, and the combined filtrate was concentrated to 2/5 of the original amount to obtain an aqueous extract concentrate.[40] 30g of processed Rhizoma polygonati, 30g of processed Rhizoma polygonati odorati, 9g of Semen cassiae and 3g of Rhizoma chuanxiong were weighed respectively, and mixed and crushed to obtain a medicinal material mixture. A 10-fold amount (based on a mass of the medicinal material mixture) of purified water was added, and the medicinal material mixture was immersed for 1h, boiled with fast fire and decocted with slow fire for 1h, and filtrated. An 8-fold amount of purified water was added, the medicinal material mixture was immersed for 1h, boiled with fast fire and decocted with slow fire for 1h again. The filtrate was combined, and the combined filtrate was concentrated to 2/5 of the original amount to obtain an aqueous extract concentrate.
Ethanol was added to the aqueous extract concentrate until the ethanol concentration reached 75%, and the mixed solution was placed in a refrigerator at 4°C for 24h. The mixed solution was mixed evenly and centrifugated, the supernatant was taken and concentrated to 2/5 of the original amount. The resulting concentrate was dried under reduced pressure, and the dried product was crushed to obtain dry paste powder. A 5Ethanol was added to the aqueous extract concentrate until the ethanol concentration reached 75%, and the mixed solution was placed in a refrigerator at 4°C for 24h. The mixed solution was mixed evenly and centrifuged, the supernatant was taken and concentrated to 2/5 of the original amount. The resulting concentrate was dried under reduced pressure, and the dried product was crushed to obtain dry paste powder. AT 5
BL-5573 high-speed stirring granulator was turned on, and parameters were set (a dry mixing LU503014 time was 5 min, a wet mixing time was 3 min, a granulation time was 4 min, a dry mixing stirring speed was 400 rpm, a wet mixing stirring speed was 500 rpm, a granulation stirring speed was 1,200 rpm, and a cutting speed was 2,500 rpm). 2 kg of dry paste powder and 1 kg of filling agent (sodium alginate:mannitol = 3:1) were added to a mixing tank, and an agitator blade was turned on for dry mixing. 90 g of 95% ethanol was evenly added in a wet mixing process, and a cutter knife was turned on.BL-5573 high-speed stirring granulator was turned on, and parameters were set (a dry mixing LU503014 time was 5 min, a wet mixing time was 3 min, a granulation time was 4 min, a dry mixing stirring speed was 400 rpm, a wet mixing stirring speed was 500 rpm, a granulation stirring speed was 1,200 rpm, and a cutting speed was 2,500 rpm). 2 kg of dry paste powder and 1 kg of filling agent (sodium alginate:mannitol = 3:1) were added to a mixing tank, and an agitator blade was turned on for dry mixing. 90 g of 95% ethanol was evenly added in a wet mixing process, and a cutter knife was turned on.
Upon completion of granulation, granules were discharged and dried at 60°C for 20 min.Upon completion of granulation, granules were discharged and dried at 60°C for 20 min.
[41] According to the appearance and the inspection items of particle size, moisture and solubility of granules in Chinese Pharmacopoeia (2020 Edition), the indicators of the brain-tonifying granules prepared in example 1 were tested. The results are as shown in Table 1, and the finished product picture is as shown in FIG 1.[41] According to the appearance and the inspection items of particle size, moisture and solubility of granules in Chinese Pharmacopoeia (2020 Edition), the indicators of the brain-tonifying granules prepared in example 1 were tested. The results are as shown in Table 1, and the finished product picture is as shown in FIG 1.
[42] Table 1 Test Results[42] Table 1 Test Results
Test Item Test ResultTest Item Test Result
Color Brown -Color Brown -
Particle size (96.18+0.28)% QualifiedParticle size (96.18+0.28)% Qualified
Water content (6.02+0.28)% QualifiedWater content (6.02+0.28)% Qualified
Solubility Dissolved without Qualified precipitationSolubility Dissolved without Qualified precipitation
[43] Example 2[43] Example 2
[44] High-temperature test: The brain-tonifying granules prepared in example 1 and brain-tonifying decoction (an aqueous extract from 30 g of processed Rhizoma polygonati, 30 g of processed Rhizoma polygonati odorati, 9 g of Semen cassiae and 3 g of Rhizoma chuanxiong in example 1) were placed in a drug stability test chamber at (60+2)°C and constant humidity respectively, samples were taken on days 0, 5 and 10 respectively to inspect characters, and the contents of total polysaccharides and ligustrazine were tested on day 10. The results showed that at high temperature, the brain-tonifying granules had uniform color without agglomeration on days 0, 5 and 10, while a part of granular precipitation appeared in the brain-tonifying decoction from day 5, and a large amount of precipitation and corruption appeared on day 10. The contents of total polysaccharides and ligustrazine were tested on day 10 (calculated according to an initial concentration of each component being 100%), and a change amount of each component was calculated. A content of total polysaccharides in the brain-tonifying granules was 98.60% of the initial concentration, and a content of ligustrazine was 98.63% of the initial concentration; after day 10, a content of total polysaccharides in the brain-tonifying decoction was 76.24% of the initial concentration, and a content of ligustrazine was 85.78% of the initial concentration.[44] High-temperature test: The brain-tonifying granules prepared in example 1 and brain-tonifying decoction (an aqueous extract from 30 g of processed Rhizoma polygonati, 30 g of processed Rhizoma polygonati odorati, 9 g of Semen cassiae and 3 g of Rhizoma chuanxiong in example 1) were placed in a drug stability test chamber at (60+2)°C and constant humidity respectively, samples were taken on days 0, 5 and 10 respectively to inspect characters, and the contents of total polysaccharides and ligustrazine were tested on day 10. The results showed that at high temperature, the brain-tonifying granules had uniform color without agglomeration on days 0, 5 and 10, while a part of granular precipitation appeared in the brain-tonifying decoction from day 5, and a large amount of precipitation and corruption appeared on day 10. The contents of total polysaccharides and ligustrazine were tested on day 10 (calculated according to an initial concentration of each component being 100%), and a change amount of each component was calculated. A content of total polysaccharides in the brain-tonifying granules was 98.60% of the initial concentration, and a content of ligustrazine was 98.63% of the initial concentration; after day 10, a content of total polysaccharides in the brain-tonifying decoction was 76.24% of the initial concentration, and a content of ligustrazine was 85.78% of the initial concentration.
[45] Acceleration test: The brain-tonifying granules prepared in example 1 and brain-tonifying decoction were placed in a drug stability test chamber at (40+2)°C and a relative humidity of 75% respectively, samples were taken in months 0, 3 and 6 respectively to inspect characters, and the contents of total polysaccharides and ligustrazine were tested in month 6. The results showed that in the acceleration test, the brain-tonifying granules had uniform color without agglomeration in months 3 and 6, 6[45] Acceleration test: The brain-tonifying granules prepared in example 1 and brain-tonifying decoction were placed in a drug stability test chamber at (40+2)°C and a relative humidity of 75% respectively, samples were taken in months 0, 3 and 6 respectively to inspect characters, and the contents of total polysaccharides and ligustrazine were tested in month 6. The results showed that in the acceleration test, the brain-tonifying granules had uniform color without agglomeration in months 3 and 6, 6
BL-5573 while obvious precipitation appeared in the brain-tonifying decoction in month 3, and a LU503014 large amount of precipitation and corruption appeared in month 6. The contents of total polysaccharides and ligustrazine were tested in month 6 (calculated according to an initial concentration of each component being 100%). À content of total polysaccharides in the brain-tonifying granules was 96.65% of the initial concentration, and a content of ligustrazine was 98.17% of the initial concentration; a content of total polysaccharides in the brain-tonifying decoction was 65.36% of the initial concentration, and a content of ligustrazine was 81.23% of the initial concentration.BL-5573 while obvious precipitation appeared in the brain-tonifying decoction in month 3, and a LU503014 large amount of precipitation and corruption appeared in month 6. The contents of total polysaccharides and ligustrazine were tested in month 6 (calculated according to an initial concentration of each component being 100%). À content of total polysaccharides in the brain-tonifying granules was 96.65% of the initial concentration, and a content of ligustrazine was 98.17% of the initial concentration; a content of total polysaccharides in the brain-tonifying decoction was 65.36% of the initial concentration, and a content of ligustrazine was 81.23% of the initial concentration.
[46] To sum up, the brain-tonifying granules of the present invention have good stability and stable quality, and have obvious advantages over the brain-tonifying decoction.[46] To sum up, the brain-tonifying granules of the present invention have good stability and stable quality, and have obvious advantages over the brain-tonifying decoction.
[47] Example 3[47] Example 3
[48] Water maze experiment method: The schematic diagram of SMG-2 water maze is as shown in FIG 2. The program was opened, the file was left-clicked, and the “Start of Experiment” was selected. At this time, a recording window popped up, and the behaviors (times of entering the blind ends and latency) of the first mouse were recorded. When the mouse swam to the step, the recording automatically stopped and the time was locked. “Finish” was clicked, and the experimental results were listed in detail. When the second mouse was ready, the above procedure was repeated. During the experimental training, the passage between point A and point B was blocked with a partition on the first day of training, and one mouse placed on the step for 10 s so that the mouse was aware of the existence of the safe area; then the mouse was placed at the starting point A and allowed to swim freely, and the times (i.e., error times) that the mouse entered the blind end 1 and the time (i.e., latency) that the mouse climbed the safe step were recorded; the mouse that could not find the step within 2 min would be directed to the safe step, and the latency would be recorded as 2 min. After the first training, the mouse was allowed to have a rest and trained again according to the same method. Other mice were trained successively. On the second day of training, the partition was placed at the point B, and the starting point for swimming was point B; the error times that the mouse entered the blind ends 1, 2 and 3 within 2 min and the latency that the mouse climbed the safe step were recorded respectively, and each mouse was trained twice continuously. The mice that could not find the step within 2 min would be directed to the end point, and the latency would be recorded as 2 min. From the third day to the fifth day of training, the partition was removed, and the starting point for swimming was point C; the error times that the mice entered the blind ends 1, 2, 3 and 4 within 2 min and the latency that the mice found the safe step were recorded, and each mouse was trained twice continuously. Upon completion of training, the mice were allowed to rest for a day, and the test was performed on the seventh day. The starting point was still point C, and the time was 2 min. The times that the mice entered the blind ends 1, 2, 3, and 4 were recorded as the error times, and the time that the mice found the safe step was recorded as the latency.[48] Water maze experiment method: The schematic diagram of SMG-2 water maze is as shown in FIG 2. The program was opened, the file was left-clicked, and the “Start of Experiment” was selected. At this time, a recording window popped up, and the behaviors (times of entering the blind ends and latency) of the first mouse were recorded. When the mouse swam to the step, the recording automatically stopped and the time was locked. “Finish” was clicked, and the experimental results were listed in detail. When the second mouse was ready, the above procedure was repeated. During the experimental training, the passage between point A and point B was blocked with a partition on the first day of training, and one mouse placed on the step for 10 s so that the mouse was aware of the existence of the safe area; then the mouse was placed at the starting point A and allowed to swim freely, and the times (i.e., error times) that the mouse entered the blind end 1 and the time (i.e., latency) that the mouse climbed the safe step were recorded ; the mouse that could not find the step within 2 min would be directed to the safe step, and the latency would be recorded as 2 min. After the first training, the mouse was allowed to have a rest and trained again according to the same method. Other mice were trained successively. On the second day of training, the score was placed at the point B, and the starting point for swimming was point B; the error times that the mouse entered the blind ends 1, 2 and 3 within 2 min and the latency that the mouse climbed the safe step were recorded respectively, and each mouse was trained twice continuously. The mice that could not find the step within 2 min would be directed to the end point, and the latency would be recorded as 2 min. From the third day to the fifth day of training, the partition was removed, and the starting point for swimming was point C; the error times that the mice entered the blind ends 1, 2, 3 and 4 within 2 min and the latency that the mice found the safe step were recorded, and each mouse was trained twice continuously. Upon completion of training, the mice were allowed to rest for a day, and the test was performed on the seventh day. The starting point was still point C, and the time was 2 min. The times that the mice entered the blind ends 1, 2, 3, and 4 were recorded as the error times, and the time that the mice found the safe step was recorded as the latency.
[49] 12 ICR mice were randomly divided into 4 groups for administration dose pre-experiment of scopolamine. A water maze experiment was used, and the experimental data were recorded and analyzed to obtain an optimal dose for modeling. 7[49] 12 ICR mice were randomly divided into 4 groups for administration dose pre-experiment of scopolamine. A water maze experiment was used, and the experimental data were recorded and analyzed to obtain an optimal dose for modeling. 7
BL-5573BL-5573
The determined experimental results of scopolamine dose for modeling are as shown in LU503014The determined experimental results of scopolamine dose for modeling are as shown in LU503014
Table 2. With the increase of scopolamine dose, the latency of the mice in the water maze also increased gradually, demonstrating that the scopolamine could decrease the learning and memory ability of the mice, and the model was successfully built. However, through data analysis, independent-samples T-test was performed on the data of the low-dose group, the middle-dose group and the blank control group, P > 0.05, showing no significant difference; the independent-samples T-test was performed on the data of the high-dose group and the blank control group, and P was 0.02, less than 0.05.Table 2. With the increase of scopolamine dose, the latency of the mice in the water maze also increased gradually, demonstrating that the scopolamine could decrease the learning and memory ability of the mice, and the model was successfully built. However, through data analysis, independent-samples T-test was performed on the data of the low-dose group, the middle-dose group and the blank control group, P > 0.05, showing no significant difference; the independent-samples T-test was performed on the data of the high-dose group and the blank control group, and P was 0.02, less than 0.05.
Therefore, the high-dose group showed a significant difference, so 3 mg/kg scopolamine was selected as the dose for modeling in the following experiment.Therefore, the high-dose group showed a significant difference, so 3 mg/kg scopolamine was selected as the dose for modeling in the following experiment.
[50] Table 2 Modeling Groups of Scopolamine and Administration Doses[50] Table 2 Modeling Groups of Scopolamine and Administration Doses
Group Administration LatencyGroup Administration Latency
Low-dose group Scopolamine (1 mg/kg) 7.24+4.00Low-dose group Scopolamine (1 mg/kg) 7.24+4.00
Middle-dose group Scopolamine (2 mg/kg) 93.56+3.19Middle-dose group Scopolamine (2 mg/kg) 93.56+3.19
High-dose group Scopolamine (3 mg/kg) 100.97+16.54High-dose group Scopolamine (3 mg/kg) 100.97+16.54
Blank control group Normal saline 60.45+7.41Blank control group Normal saline 60.45+7.41
[51] 12 ICR mice were randomly divided into 4 groups for administration dose pre-experiment of brain-tonifying granules. A water maze experiment was used, and the experimental data were recorded and analyzed to obtain an approximate dose range of the brain-tonifying granules. The administration dose used was converted from the administration dose of the brain-tonifying decoction, and the administration dose of mice was calculated by the following pharmacokinetic formula: (ONE[51] 12 ICR mice were randomly divided into 4 groups for administration dose pre-experiment of brain-tonifying granules. A water maze experiment was used, and the experimental data were recorded and analyzed to obtain an approximate dose range of the brain-tonifying granules. The administration dose used was converted from the administration dose of the brain-tonifying decoction, and the administration dose of mice was calculated by the following pharmacokinetic formula: (ONE
[52][52]
[53] where Kmice = 9.1, Khuman = 10.6. The body weight of mice is calculated as 20 g, and the body weight of humans is calculated as 60 kg, so a ratio of the body surface area of adults to the body surface area of mice is 242.47:1.[53] where Kmice = 9.1, Khuman = 10.6. The body weight of mice is calculated as 20 g, and the body weight of humans is calculated as 60 kg, so a ratio of the body surface area of adults to the body surface area of mice is 242.47:1.
[54] As shown in Table 3, the latency in the negative control group was the longest, while the latency in the administration groups was significantly less than that in the negative control group. However, the independent-samples T-test was performed on the data of the low-dose group, the middle-dose group and the negative control group by[54] As shown in Table 3, the latency in the negative control group was the longest, while the latency in the administration groups was significantly less than that in the negative control group. However, the independent-samples T-test was performed on the data of the low-dose group, the middle-dose group and the negative control group by
IBM SPSS Statistics 23, P > 0.05, showing no significant difference; P of the T-test between the high-dose group and the negative control group was less than 0.05, showing a significant difference. Therefore, the administration dose of the brain-tonifying granules should be 8 g/kg in the following experiment.IBM SPSS Statistics 23, P > 0.05, showing no significant difference; P of the T-test between the high-dose group and the negative control group was less than 0.05, showing a significant difference. Therefore, the administration dose of the brain-tonifying granules should be 8 g/kg in the following experiment.
[55] Table 3 Pre-experiment Groups of Brain-tonifying Granules and Administration[55] Table 3 Pre-experiment Groups of Brain-tonifying Granules and Administration
DosesRates
Group Drug Administration Latency (n=3)Group Drug Administration Latency (n=3)
Low-dose group Brain-tonifying granules 67.68+5.42 (2 g/kg)Low-dose group Brain-tonifying granules 67.68+5.42 (2 g/kg)
Middle-dose group Brain-tonifying granules 84.50+10.45 (4 g/kg) 8Middle-dose group Brain-tonifying granules 84.50+10.45 (4 g/kg) 8
BL-5573BL-5573
High-dose group Brain-tonifying granules 53.19+6.44 LUS03014 (8 g/kg)High-dose group Brain-tonifying granules 53.19+6.44 LUS03014 (8 g/kg)
Blank control group Drinking water 99.25+16.25Blank control group Drinking water 99.25+16.25
[56] 60 mice were divided into 6 groups, 10 mice in each group, which were a blank control group, a negative control group, a high-dose group, a middle-dose group and a low-dose group respectively. In the aspect of modeling, the blank control group was injected intraperitoneally with normal saline, while the other groups were injected intraperitoneally with scopolamine at a dose of 3 mg/kg. In the aspect of administration, the blank control group and the negative control group were given drinking water, the high-dose, middle-dose and low-dose groups were given brain-tonifying granules, and the positive control group was given a brain-tonifying oral solution (the brain-tonifying oral solution was prepared according to the method in CN107308323A, wherein a mass ratio of processed Rhizoma polygonati to processed Rhizoma polygonati odorati to[56] 60 mice were divided into 6 groups, 10 mice in each group, which were a blank control group, a negative control group, a high-dose group, a middle-dose group and a low-dose group respectively. In the aspect of modeling, the blank control group was injected intraperitoneally with normal saline, while the other groups were injected intraperitoneally with scopolamine at a dose of 3 mg/kg. In the aspect of administration, the blank control group and the negative control group were given drinking water, the high-dose, middle-dose and low-dose groups were given brain-tonifying granules, and the positive control group was given a brain- tonifying oral solution (the brain-tonifying oral solution was prepared according to the method in CN107308323A, wherein a mass ratio of processed Rhizoma polygonati to processed Rhizoma polygonati odorati to
Semen cassiae to Rhizoma chuanxiong was 30:30:9:3), as shown in Table 4.Semen cassiae to Rhizoma chuanxiong was 30:30:9:3), as shown in Table 4.
[57] Table 4 Functional Experimental Groups of Brain-tonifying Granules (n=10)[57] Table 4 Functional Experimental Groups of Brain-tonifying Granules (n=10)
Group Drug for Modeling AdministrationGroup Drug for Modeling Administration
Blank control group Normal saline Drinking waterBlank control group Normal saline Drinking water
Negative control group Scopolamine (3 mg/kg) Drinking waterNegative control group Scopolamine (3 mg/kg) Drinking water
High-dose group Scopolamine (3 mg/kg) Brain-tonifying granules (16 g/kg/d)High-dose group Scopolamine (3 mg/kg) Brain-tonifying granules (16 g/kg/d)
Middle-dose group Scopolamine (3 mg/kg) Brain-tonifying granules (8 g/kg/d)Middle-dose group Scopolamine (3 mg/kg) Brain-tonifying granules (8 g/kg/d)
Low-dose group Scopolamine (3 mg/kg) Brain-tonifying granules (4 g/kg/d)Low-dose group Scopolamine (3 mg/kg) Brain-tonifying granules (4 g/kg/d)
Brain-tonifying oral Scopolamine (3 mg/kg) Brain-tonifying oral solution (6 solution group ml/kg/d)Brain-tonifying oral Scopolamine (3 mg/kg) Brain-tonifying oral solution (6 solution group ml/kg/d)
[58] The water maze experimental results are as shown in Table 5 and FIG 3. As shown in the figure, the latency of the blank control group in the water maze was the shortest, while the latency of the negative control group was the longest. The independent-samples T-test was performed on the data of the two groups, and P was 0.01, indicating that the model was successfully built. For the latency of mice in the low-dose group, the brain-tonifying granules had a certain improvement effect on the learning and memory ability of the mice, but the independent-samples T-test showed no significant difference with the negative control group. The independent-samples T-test was performed on the data of the middle-dose group, the high-dose group and the negative control group, and P was 0.040 and 0.040 respectively, showing a significant difference. Therefore, the water maze experiment showed that the brain-tonifying granules were positive in improving the learning and memory ability. For the brain-tonifying oral solution group, the latency was shorter than that of the brain-tonifying granules group, but no significant difference was shown.[58] The water maze experimental results are as shown in Table 5 and FIG 3. As shown in the figure, the latency of the blank control group in the water maze was the shortest, while the latency of the negative control group was the longest . The independent-samples T-test was performed on the data of the two groups, and P was 0.01, indicating that the model was successfully built. For the latency of mice in the low-dose group, the brain-tonifying granules had a certain improvement effect on the learning and memory ability of the mice, but the independent-samples T-test showed no significant difference with the negative control group. The independent-samples T-test was performed on the data of the middle-dose group, the high-dose group and the negative control group, and P was 0.040 and 0.040 respectively, showing a significant difference. Therefore, the water maze experiment showed that the brain-tonifying granules were positive in improving the learning and memory ability. For the brain-tonifying oral solution group, the latency was shorter than that of the brain-tonifying granules group, but no significant difference was shown.
[59] Table 5 Water Maze Experiment of Brain-tonifying Granules[59] Table 5 Water Maze Experiment of Brain-tonifying Granules
Mouse Blank Negative Low-dose Middle-dose High-dose NegativeMouse Blank Negative Low-dose Middle-dose High-dose Negative
No. Control Control Group Group Group ControlNo. Control Control Group Group Group Control
Group Group Group 1 46.23 120 86.54 72.91 82.21 42.61 2 59.42 96.48 75.31 58.37 48.46 66.94 9Group Group Group 1 46.23 120 86.54 72.91 82.21 42.61 2 59.42 96.48 75.31 58.37 48.46 66.94 9
BL-5573 3 32.33 38.64 63.21 72.35 120 4937 14509014 4 31.49 93.86 64.52 71.29 49.65 74.29 29.87 104.67 59.82 73.68 55.26 43.61 6 60.54 112.32 120 66.91 120 85.87 7 120 107.29 109.87 110.74 49.13 67.14 8 38.24 92.81 100.45 70.11 38.16 69.87 9 49.51 120 120 68.07 111.27 69.54 61.68 120 62.76 65.81 43.29 40.09BL-5573 3 32.33 38.64 63.21 72.35 120 4937 14509014 4 31.49 93.86 64.52 71.29 49.65 74.29 29.87 104.67 59.82 73.68 55.26 4 3.61 6 60.54 112.32 120 66.91 120 85.87 7 120 107.29 109.87 110.74 49.13 67.14 8 38.24 92.81 100.45 70.11 38.16 69.87 9 49. 51 120 120 68.07 111.27 69.54 61.68 120 62.76 65.81 43.29 40.09
[60] Finally, it should be stated that the foregoing are only the preferred embodiments of the present invention, but are not intended to limit the present invention.[60] Finally, it should be stated that the foregoing are only the preferred embodiments of the present invention, but are not intended to limit the present invention.
Although the present invention is described in detail by reference to the above-mentioned embodiments, modifications to the technical solutions recorded in the 5 above-mentioned embodiments, or equivalent substitutions to a part of technical characteristics thereof may be made by those skilled in the art still. Any modifications, equivalent substitutions or improvements made within the spirit and principles of the present invention should be regarded to fall into the protection scope of the present invention. 10Although the present invention is described in detail by reference to the above-mentioned embodiments, modifications to the technical solutions recorded in the 5 above-mentioned embodiments, or equivalent substitutions to a part of technical characteristics thereof may be made by those skilled in the art still. Any modifications, equivalent substitutions or improvements made within the spirit and principles of the present invention should be regarded to fall into the protection scope of the present invention. 10
Claims (8)
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CN202210431160.6A CN114569671A (en) | 2022-04-22 | 2022-04-22 | Brain-nourishing granule and preparation method thereof |
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CN105194318A (en) * | 2015-10-23 | 2015-12-30 | 韩俊峰 | Compound traditional Chinese medicine brain-strengthening decoction and preparation method thereof |
CN107308323B (en) * | 2017-06-26 | 2020-08-18 | 杭州寿而健健康产品有限公司 | Brain-nourishing oral liquid and its preparation process |
CN110882323B (en) * | 2019-06-17 | 2022-04-29 | 广西中医药大学附属瑞康医院 | Granules for enhancing constitution of sub-healthy people and preparation method thereof |
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