CN108126062B - Oral traditional Chinese medicine composition for treating depression, preparation and preparation method thereof - Google Patents
Oral traditional Chinese medicine composition for treating depression, preparation and preparation method thereof Download PDFInfo
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- CN108126062B CN108126062B CN201810196624.3A CN201810196624A CN108126062B CN 108126062 B CN108126062 B CN 108126062B CN 201810196624 A CN201810196624 A CN 201810196624A CN 108126062 B CN108126062 B CN 108126062B
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Abstract
The invention belongs to the field of traditional Chinese medicines, and particularly relates to an oral traditional Chinese medicine composition for treating depression, a preparation and a preparation method thereof. The oral traditional Chinese medicine composition for treating depression is prepared from pharmaceutically acceptable pharmaceutic adjuvants and radix bupleuri, angelica sinensis, radix paeoniae alba, cassia twig, Crinum asiaticum and pleurotus citrinopileatus, wherein the radix bupleuri, the angelica sinensis, the radix paeoniae alba, the cassia twig and the pleurotus citrinopileatus are extracted by a water extraction and alcohol precipitation method, and the Crinum asiaticum is extracted by a steam distillation method to obtain a volatile oil component with the relative density of less than 1.0. The dosage form of the oral traditional Chinese medicine composition is preferably oral liquid. The oral Chinese medicinal composition has good therapeutic effect and safety on depression.
Description
Technical Field
The invention belongs to the field of traditional Chinese medicines, and particularly relates to an oral traditional Chinese medicine composition for treating depression, a preparation and a preparation method thereof.
Background
Depression is a mood disorder syndrome manifested primarily as marked and persistent depressed mood, pessimistic and disgusted self, diminished energy, altered appetite, more or less sleep, reduced attention; in the absence of social interaction desire and exploration desire, serious patients even have suicidal tendency. The causes and mechanisms of depression are not fully understood at present. It is generally accepted that depression may be the result of the interaction of physiological, psychological and social factors. Increased pace of life and increased work, learning, and social stress may be external environmental factors that contribute to depression. The prevalence rate of Chinese depression is reported to be about 3% -5%, and the regional difference of the prevalence rate is large. The incidence of Chinese depression has increased by 10-20 times in recent 30 years and still shows an increasing trend, and the Chinese depression becomes a neurologic disease which seriously affects the public health of society and even the personal safety of patients.
Modern medicine mainly adopts chemical drugs to regulate certain related neurotransmitters to achieve the purpose of controlling clinical symptoms of depression. Chemical drugs that have been marketed include: tricyclic drugs, monoamine oxidase inhibitors, 5-hydroxytryptamine reuptake inhibitors, norepinephrine reuptake inhibitors, dual 5-hydroxytryptamine and norepinephrine reuptake inhibitors, 5-hydroxytryptamine receptor blockers, and the like, and specific drugs include mirtazapine, duloxetine, imipramine, and the like. The medicines all have obvious side effects of mental systems, such as headache, nausea, insomnia and the like.
Research on traditional Chinese medicine antidepressant medicaments has already made certain progress. At present, Chinese herbal compound medicines such as bupleurum root, dragon bone and oyster soup, pinellia tuber and magnolia officinalis soup, liquorice and Chinese date soup, Jiawei lily and rehmannia soup, Xiaojianzhong soup, jieyu albizia soup, bupleurum root and liver soothing powder, Xiaoyao powder, Yueju pill and the like have certain treatment effect on depression and good safety (research progress of Wanyan Wang, Chenge Xiang and antidepressant Chinese herbal compound medicines, 2009, 11 (4): 6-9.). In the research of single medicinal material, St.John's wort of Hypericum of Guttiferae, Morinda officinalis of Morinda of Rubiaceae, Cimicifuga racemosa of Ranunculaceae, and Panax ginseng of Araliaceae have been found to have antidepressant effect. However, at present, the existing anti-depression Chinese medicines in China have few varieties and lack compound preparation products.
Disclosure of Invention
In view of the above prior art, one of the objectives of the present invention is to provide an oral Chinese medicinal composition for treating depression. In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
an oral traditional Chinese medicine composition for treating depression is prepared from pharmaceutically acceptable pharmaceutical excipients and the following traditional Chinese medicine raw materials: radix bupleuri, angelica, white peony root, cassia twig, crinum asiaticum and pleurotus citrinopileatus; wherein bupleuri radix, radix Angelicae sinensis, radix Paeoniae alba, ramulus Cinnamomi, and Pleurotus Citrinopileatus Sing are extracted by water extraction and ethanol precipitation method, and Crinum flower is extracted by steam distillation method to obtain volatile oil component with relative density of below 1.0.
Preferably, the Chinese medicinal materials comprise the following raw materials in parts by weight: 21-35 parts of radix bupleuri, 16-20 parts of angelica sinensis, 16-20 parts of radix paeoniae alba, 7-13 parts of cassia twig, 2-7 parts of crinum asiaticum and 2-6 parts of pleurotus citrinopileatus.
Preferably, the Chinese medicinal materials comprise the following raw materials in parts by weight: 33 parts of bupleurum, 19 parts of angelica, 19 parts of white peony root, 12 parts of cassia twig, 6 parts of crinum asiaticum and 5 parts of pleurotus citrinopileatus.
Preferably, the Chinese medicinal materials comprise the following raw materials in parts by weight: 30 parts of radix bupleuri, 18 parts of angelica, 18 parts of radix paeoniae alba, 11 parts of cassia twig, 3 parts of crinum asiaticum flower and 4 parts of pleurotus citrinopileatus.
Preferably, the Chinese medicinal materials comprise the following raw materials in parts by weight: 27 parts of radix bupleuri, 18 parts of angelica, 17 parts of radix paeoniae alba, 9 parts of cassia twig, 5 parts of crinum asiaticum flower and 4 parts of pleurotus citrinopileatus.
Preferably, the Chinese medicinal materials comprise the following raw materials in parts by weight: 25 parts of bupleurum, 19 parts of angelica, 17 parts of white peony root, 10 parts of cassia twig, 6 parts of crinum asiaticum and 4 parts of pleurotus citrinopileatus.
Preferably, the Chinese medicinal materials comprise the following raw materials in parts by weight: 22 parts of radix bupleuri, 17 parts of angelica, 18 parts of radix paeoniae alba, 8 parts of cassia twig, 3 parts of crinum asiaticum flower and 3 parts of pleurotus citrinopileatus.
On the other hand, the invention provides a traditional Chinese medicine oral liquid for treating depression, which is prepared from pharmaceutically acceptable pharmaceutical excipients and the following traditional Chinese medicine raw materials: radix bupleuri, angelica, white peony root, cassia twig, crinum asiaticum and pleurotus citrinopileatus; wherein the Chinese medicinal materials comprise the following raw materials in parts by weight: 21-35 parts of radix bupleuri, 16-20 parts of angelica sinensis, 16-20 parts of radix paeoniae alba, 7-13 parts of cassia twig, 2-7 parts of crinum asiaticum and 2-6 parts of pleurotus citrinopileatus; wherein the bupleurum, the angelica, the white paeony root, the cassia twig and the pleurotus citrinopileatus are extracted by a water extraction and alcohol precipitation method, and the crinum asiaticum is extracted by a steam distillation method to obtain a volatile oil component with the relative density of less than 1.0; the pharmaceutically acceptable pharmaceutic adjuvant comprises beta-cyclodextrin and polysorbate-80.
In another aspect of the present invention, a preparation method of the above traditional Chinese medicine oral liquid is provided, which comprises the following steps:
A. respectively crushing bupleurum, angelica, white paeony root, cassia twig and pleurotus citrinopileatus according to the formula amount, sieving with a 50-mesh sieve, mixing to obtain medicinal material coarse powder, adding water for decocting for 2 times, adding water with the weight 7 times of the medicinal material coarse powder for decocting for 4 hours for the 1 st time, adding water with the weight 3 times of the medicinal material coarse powder for decocting for 2 hours for the 2 nd time, filtering and combining water decoction, concentrating to obtain a concentrated solution with the relative density of 1.20, standing and cooling, adding ethanol into the concentrated solution to ensure that the volume percentage of the ethanol is 75 percent, standing overnight at 4 ℃, filtering to remove insoluble substances, collecting filtrate, distilling under reduced pressure to remove the ethanol to obtain a refined solution, concentrating the refined solution under reduced pressure to obtain a fluid extract with the relative density of 1.22-;
B. grinding crinum asiaticum into fine powder, adding into volatile oil extractor, adding into 10 per gram of fine powder～Adding 13 ml of water into the fine powder, soaking for 1 hour, extracting by a steam distillation method at the extraction temperature of 75 ℃ for 8-11 hours, and separating volatile oil with the relative density of less than 1.0 for later use;
C. b, taking beta-cyclodextrin according to the proportion that 7 g of beta-cyclodextrin is used for each milliliter of volatile oil, adding distilled water to prepare a saturated aqueous solution at the temperature of 50 ℃, slowly dripping the volatile oil obtained in the step B into the saturated aqueous solution of the beta-cyclodextrin under the condition of heat preservation, stirring for 1 hour, and freeze-drying to obtain a beta-cyclodextrin inclusion compound;
D. and D, adding the beta-cyclodextrin inclusion compound obtained in the step C into the fluid extract obtained in the step A, adding polysorbate-80 according to the proportion that 0.8 g of polysorbate-80 is added into each 100 ml of the fluid extract, uniformly stirring, and subpackaging to obtain the product.
Preferably, the relative density of the fluid extract in the step A is 1.24; in step B, 12 ml of water is added into each gram of fine powder, and the extraction time is 10 hours.
The invention also provides a traditional Chinese medicine oral tablet for treating depression, which is prepared from pharmaceutically acceptable pharmaceutical excipients and the following traditional Chinese medicine raw materials: radix bupleuri, angelica, white peony root, cassia twig, crinum asiaticum and pleurotus citrinopileatus; wherein the Chinese medicinal materials comprise the following raw materials in parts by weight: 21-35 parts of radix bupleuri, 16-20 parts of angelica sinensis, 16-20 parts of radix paeoniae alba, 7-13 parts of cassia twig, 2-7 parts of crinum asiaticum and 2-6 parts of pleurotus citrinopileatus; wherein the bupleurum, the angelica, the white paeony root, the cassia twig and the pleurotus citrinopileatus are extracted by a water extraction and alcohol precipitation method, and the crinum asiaticum is extracted by a steam distillation method to obtain a volatile oil component with the relative density of less than 1.0; the auxiliary materials of the tablet comprise beta-cyclodextrin, starch, microcrystalline cellulose and magnesium stearate, and the preparation method of the granule comprises the following steps:
A. respectively crushing bupleurum, angelica, white paeony root, cassia twig and pleurotus citrinopileatus according to the prescription amount, sieving with a 50-mesh sieve, mixing to obtain crude medicinal powder, adding water for decocting for 2 times, adding water 7 times the weight of the crude medicinal powder for decocting for 4 hours for the 1 st time, adding water 3 times the weight of the crude medicinal powder for decocting for 2 hours for the 2 nd time, filtering and combining water decoction, concentrating to obtain concentrated solution with the relative density of 1.20, standing and cooling, adding ethanol into the concentrated solution to ensure that the volume percentage of the ethanol is 75 percent, standing overnight at 4 ℃, filtering to remove insoluble substances, collecting filtrate, distilling under reduced pressure to remove the ethanol to obtain refined solution, concentrating the refined solution under reduced pressure to obtain fluid extract with the relative density of 1.24 for later use when the;
B. grinding crinum asiaticum into fine powder according to the prescription amount, adding the fine powder into a volatile oil extractor, adding water into the fine powder according to the proportion that 12 milliliters of water is added into each gram of the fine powder, soaking for 1 hour, extracting by a steam distillation method at the extraction temperature of 75 ℃ for 10 hours, and separating the volatile oil with the relative density of less than 1.0 for later use;
C. b, taking beta-cyclodextrin according to the proportion that 7 g of beta-cyclodextrin is used for each milliliter of volatile oil, adding distilled water to prepare a saturated aqueous solution at the temperature of 50 ℃, slowly dripping the volatile oil obtained in the step B into the saturated aqueous solution of the beta-cyclodextrin under the condition of heat preservation, stirring for 1 hour, and freeze-drying to obtain a beta-cyclodextrin inclusion compound;
D. and D, adding the beta-cyclodextrin inclusion compound obtained in the step C into the fluid extract obtained in the step A, adding starch and microcrystalline cellulose into the fluid extract, mixing, performing wet granulation, sieving with a 20-mesh sieve, performing granulation, drying at 60 ℃, sieving with a 18-mesh sieve, granulating, adding magnesium stearate, and performing tabletting. Wherein the dosage of starch and microcrystalline cellulose is 0.4 times and 0.3 times of the weight of the fluid extract respectively, and the dosage of magnesium stearate is 0.01 times of the total weight of the dry granules.
The Bupleurum root in the technical scheme of the invention is the dried root of Bupleurum chinense DC or Bupleurum scorzonerifolium Willd which belongs to the family of Umbelliferae. Is described in the pharmacopoeia of the people's republic of China 2015 edition.
The Angelica sinensis in the technical scheme of the invention is the dried root of Angelica sinensis (Oliv.) Diels of Umbelliferae. Is described in the pharmacopoeia of the people's republic of China 2015 edition.
The white peony root is the dry root of Paeonia lactiflora pall of Ranunculaceae. Is described in the pharmacopoeia of the people's republic of China 2015 edition.
The cassia twig in the technical scheme of the invention is a dry twig of Cinnamomum cassia Cassia Presl of Lauraceae. Is described in the pharmacopoeia of the people's republic of China 2015 edition.
The Crinum asiaticum flower in the technical scheme of the invention is a dried flower of Crinum asiaticum L. Is recorded in the book of Chinese herbal medicine Association and the book of Chinese materia medica (Dai medicated roll). The medicine is mostly taken as leaf and bulb, and is fresh to be taken as flower.
The pleurotus citrinopileatus is a dried fruiting body of pleurotus citrinopileatus Sing in pleurotus of the pleurotus family of the invention.
The beta-cyclodextrin is cyclic oligosaccharide formed by combining 7 glucoses generated by acting cyclodextrin glucosyltransferase on starch by alpha-1, 4-glycosidic bonds; the polysorbate-80 in the technical scheme of the invention is polyoxyethylene 20 sorbitan oleate polymerized by sorbitan oleate and ethylene oxide. Beta-cyclodextrin and polysorbate-80 are common pharmaceutical excipients and are recorded in the pharmacopoeia of the people's republic of China 2015.
The inventor discovers in experimental research that the compound prescription consisting of the bupleurum, the angelica, the white paeony root and the cassia twig has a certain depression resistance; the Crinum asiaticum does not have the antidepressant effect, but has the synergistic effect on the compound of bupleurum, angelica, white paeony root and cassia twig, and the pleurotus citrinopileatus can inhibit the toxic and side effect of the Crinum asiaticum. The compound prescription consisting of six medicinal materials of bupleurum, angelica, white paeony root, cassia twig, Crinum asiaticum and pleurotus citrinopileatus has good anti-depression effect and good safety.
Detailed Description
The invention is further illustrated by the following examples. It should be understood that the following examples are only for illustrating the present invention, and are not intended to limit the scope of the present invention.
EXAMPLE 1 Chinese medicinal oral liquid for treating Depression and preparation thereof
The preparation method comprises the following steps:
A. respectively crushing bupleurum, angelica, white paeony root, cassia twig and pleurotus citrinopileatus according to the prescription amount, sieving with a 50-mesh sieve, mixing to obtain crude medicinal powder, adding water for decocting for 2 times, adding water 7 times the weight of the crude medicinal powder for decocting for 4 hours for the 1 st time, adding water 3 times the weight of the crude medicinal powder for decocting for 2 hours for the 2 nd time, filtering and combining water decoction, concentrating to obtain concentrated solution with the relative density of 1.20, standing and cooling, adding ethanol into the concentrated solution to ensure that the volume percentage of the ethanol is 75 percent, standing overnight at 4 ℃, filtering to remove insoluble substances, collecting filtrate, distilling under reduced pressure to remove the ethanol to obtain refined solution, concentrating the refined solution under reduced pressure to obtain fluid extract with the relative density of 1.24 for later use when the;
B. grinding crinum asiaticum into fine powder according to the prescription amount, adding the fine powder into a volatile oil extractor, adding water into the fine powder according to the proportion that 12 milliliters of water is added into each gram of the fine powder, soaking for 1 hour, extracting by a steam distillation method at the extraction temperature of 75 ℃ for 10 hours, and separating the volatile oil with the relative density of less than 1.0 for later use;
C. b, taking beta-cyclodextrin according to the proportion that 7 g of beta-cyclodextrin is used for each milliliter of volatile oil, adding distilled water to prepare a saturated aqueous solution at the temperature of 50 ℃, slowly dripping the volatile oil obtained in the step B into the saturated aqueous solution of the beta-cyclodextrin under the condition of heat preservation, stirring for 1 hour, and freeze-drying to obtain a beta-cyclodextrin inclusion compound;
D. and D, adding the beta-cyclodextrin inclusion compound obtained in the step C into the fluid extract obtained in the step A, adding polysorbate-80 according to the proportion that 0.8 g of polysorbate-80 is added into each 100 ml of the fluid extract, uniformly stirring, and subpackaging to obtain the product.
EXAMPLE 2 Chinese medicinal oral liquid for treating Depression and preparation thereof
The preparation method comprises the following steps:
A. respectively crushing bupleurum, angelica, white paeony root, cassia twig and pleurotus citrinopileatus according to the prescription amount, sieving with a 50-mesh sieve, mixing to obtain crude medicinal powder, adding water for decocting for 2 times, adding water 7 times the weight of the crude medicinal powder for decocting for 4 hours for the 1 st time, adding water 3 times the weight of the crude medicinal powder for decocting for 2 hours for the 2 nd time, filtering and combining water decoction, concentrating to obtain concentrated solution with the relative density of 1.20, standing and cooling, adding ethanol into the concentrated solution to ensure that the volume percentage of the ethanol is 75 percent, standing overnight at 4 ℃, filtering to remove insoluble substances, collecting filtrate, distilling under reduced pressure to remove the ethanol to obtain refined solution, concentrating the refined solution under reduced pressure to obtain fluid extract with the relative density of 1.24 for later use when the;
B. grinding crinum asiaticum into fine powder according to the prescription amount, adding the fine powder into a volatile oil extractor, adding water into the fine powder according to the proportion that 12 milliliters of water is added into each gram of the fine powder, soaking for 1 hour, extracting by a steam distillation method at the extraction temperature of 75 ℃ for 10 hours, and separating the volatile oil with the relative density of less than 1.0 for later use;
C. b, taking beta-cyclodextrin according to the proportion that 7 g of beta-cyclodextrin is used for each milliliter of volatile oil, adding distilled water to prepare a saturated aqueous solution at the temperature of 50 ℃, slowly dripping the volatile oil obtained in the step B into the saturated aqueous solution of the beta-cyclodextrin under the condition of heat preservation, stirring for 1 hour, and freeze-drying to obtain a beta-cyclodextrin inclusion compound;
D. and D, adding the beta-cyclodextrin inclusion compound obtained in the step C into the fluid extract obtained in the step A, adding polysorbate-80 according to the proportion that 0.8 g of polysorbate-80 is added into each 100 ml of the fluid extract, uniformly stirring, and subpackaging to obtain the product.
EXAMPLE 3 Chinese medicinal oral liquid for treating Depression and preparation thereof
The preparation method comprises the following steps:
A. respectively crushing bupleurum, angelica, white paeony root, cassia twig and pleurotus citrinopileatus according to the prescription amount, sieving with a 50-mesh sieve, mixing to obtain crude medicinal powder, adding water for decocting for 2 times, adding water 7 times the weight of the crude medicinal powder for decocting for 4 hours for the 1 st time, adding water 3 times the weight of the crude medicinal powder for decocting for 2 hours for the 2 nd time, filtering and combining water decoction, concentrating to obtain concentrated solution with the relative density of 1.20, standing and cooling, adding ethanol into the concentrated solution to ensure that the volume percentage of the ethanol is 75 percent, standing overnight at 4 ℃, filtering to remove insoluble substances, collecting filtrate, distilling under reduced pressure to remove the ethanol to obtain refined solution, concentrating the refined solution under reduced pressure to obtain fluid extract with the relative density of 1.24 for later use when the;
B. grinding crinum asiaticum into fine powder according to the prescription amount, adding the fine powder into a volatile oil extractor, adding water into the fine powder according to the proportion that 12 milliliters of water is added into each gram of the fine powder, soaking for 1 hour, extracting by a steam distillation method at the extraction temperature of 75 ℃ for 10 hours, and separating the volatile oil with the relative density of less than 1.0 for later use;
C. b, taking beta-cyclodextrin according to the proportion that 7 g of beta-cyclodextrin is used for each milliliter of volatile oil, adding distilled water to prepare a saturated aqueous solution at the temperature of 50 ℃, slowly dripping the volatile oil obtained in the step B into the saturated aqueous solution of the beta-cyclodextrin under the condition of heat preservation, stirring for 1 hour, and freeze-drying to obtain a beta-cyclodextrin inclusion compound;
D. and D, adding the beta-cyclodextrin inclusion compound obtained in the step C into the fluid extract obtained in the step A, adding polysorbate-80 according to the proportion that 0.8 g of polysorbate-80 is added into each 100 ml of the fluid extract, uniformly stirring, and subpackaging to obtain the product.
EXAMPLE 4 Chinese medicinal oral liquid for treating Depression and preparation thereof
The preparation method comprises the following steps:
A. respectively crushing bupleurum, angelica, white paeony root, cassia twig and pleurotus citrinopileatus according to the prescription amount, sieving with a 50-mesh sieve, mixing to obtain crude medicinal powder, adding water for decocting for 2 times, adding water 7 times the weight of the crude medicinal powder for decocting for 4 hours for the 1 st time, adding water 3 times the weight of the crude medicinal powder for decocting for 2 hours for the 2 nd time, filtering and combining water decoction, concentrating to obtain concentrated solution with the relative density of 1.20, standing and cooling, adding ethanol into the concentrated solution to ensure that the volume percentage of the ethanol is 75 percent, standing overnight at 4 ℃, filtering to remove insoluble substances, collecting filtrate, distilling under reduced pressure to remove the ethanol to obtain refined solution, concentrating the refined solution under reduced pressure to obtain fluid extract with the relative density of 1.24 for later use when the;
B. grinding crinum asiaticum into fine powder according to the prescription amount, adding the fine powder into a volatile oil extractor, adding water into the fine powder according to the proportion that 12 milliliters of water is added into each gram of the fine powder, soaking for 1 hour, extracting by a steam distillation method at the extraction temperature of 75 ℃ for 10 hours, and separating the volatile oil with the relative density of less than 1.0 for later use;
C. b, taking beta-cyclodextrin according to the proportion that 7 g of beta-cyclodextrin is used for each milliliter of volatile oil, adding distilled water to prepare a saturated aqueous solution at the temperature of 50 ℃, slowly dripping the volatile oil obtained in the step B into the saturated aqueous solution of the beta-cyclodextrin under the condition of heat preservation, stirring for 1 hour, and freeze-drying to obtain a beta-cyclodextrin inclusion compound;
D. and D, adding the beta-cyclodextrin inclusion compound obtained in the step C into the fluid extract obtained in the step A, adding polysorbate-80 according to the proportion that 0.8 g of polysorbate-80 is added into each 100 ml of the fluid extract, uniformly stirring, and subpackaging to obtain the product.
EXAMPLE 5 Chinese medicinal oral liquid for treating Depression and preparation thereof
The preparation method comprises the following steps:
A. respectively crushing bupleurum, angelica, white paeony root, cassia twig and pleurotus citrinopileatus according to the prescription amount, sieving with a 50-mesh sieve, mixing to obtain crude medicinal powder, adding water for decocting for 2 times, adding water 7 times the weight of the crude medicinal powder for decocting for 4 hours for the 1 st time, adding water 3 times the weight of the crude medicinal powder for decocting for 2 hours for the 2 nd time, filtering and combining water decoction, concentrating to obtain concentrated solution with the relative density of 1.20, standing and cooling, adding ethanol into the concentrated solution to ensure that the volume percentage of the ethanol is 75 percent, standing overnight at 4 ℃, filtering to remove insoluble substances, collecting filtrate, distilling under reduced pressure to remove the ethanol to obtain refined solution, concentrating the refined solution under reduced pressure to obtain fluid extract with the relative density of 1.24 for later use when the;
B. grinding crinum asiaticum into fine powder according to the prescription amount, adding the fine powder into a volatile oil extractor, adding water into the fine powder according to the proportion that 12 milliliters of water is added into each gram of the fine powder, soaking for 1 hour, extracting by a steam distillation method at the extraction temperature of 75 ℃ for 10 hours, and separating the volatile oil with the relative density of less than 1.0 for later use;
C. b, taking beta-cyclodextrin according to the proportion that 7 g of beta-cyclodextrin is used for each milliliter of volatile oil, adding distilled water to prepare a saturated aqueous solution at the temperature of 50 ℃, slowly dripping the volatile oil obtained in the step B into the saturated aqueous solution of the beta-cyclodextrin under the condition of heat preservation, stirring for 1 hour, and freeze-drying to obtain a beta-cyclodextrin inclusion compound;
D. and D, adding the beta-cyclodextrin inclusion compound obtained in the step C into the fluid extract obtained in the step A, adding polysorbate-80 according to the proportion that 0.8 g of polysorbate-80 is added into each 100 ml of the fluid extract, uniformly stirring, and subpackaging to obtain the product.
Example 6 anti-Depression pharmacodynamics and safety test
First, establishment of animal model
The SPF-grade healthy male SD rats with the weight of 180-220 g are provided by Beijing Wittingle animal experiment center, and are bred in the experiment animal center of Heilongjiang Chinese medicine university, free drinking and eating are kept during the experiment, the breeding environment temperature is 23-25 ℃, the humidity is 50-60%, and the male SD rats are adaptively bred for 1 week before the experiment.
72 rats were taken and received 35 days of chronic mild unpredictable stress stimuli including ice water swimming, day-to-day reversal, binding restraint, tail-pinching, shaking, fasting, and water deprivation. Each group of animals was randomly given one stimulation per day, and the same stimulation was used up to 5 times. The specific procedure for each stress was as follows:
(1) swimming with ice water: the rat is put into a 20 liter bucket filled with cold water at 4 ℃ for 5 minutes;
(2) the day and night are reversed: placing the rat in a dark space surrounded by black cloth for 12 hours in the daytime, and placing the rat in a bright space irradiated by an incandescent lamp for 12 hours at night;
(3) binding and restraining, namely placing the rat in a 550 ml mineral water bottle to enable the rat not to move freely for 3 hours;
(4) tail clamping: clamping the part 1 cm away from the root of the tail by using a bamboo clamp, and making the rat send out grief for 2 minutes;
(5) oscillating: the rats were placed in a horizontal shaker and shaking was stopped after 2 minutes;
(6) fasting: stopping feeding the feed for 24 hours;
(7) water forbidding: the water supply was stopped for 24 hours.
Grouping and administration of model animals
After the molding was completed, the rats were randomly divided into 9 groups of 8 rats each. And (3) after the first group of the models is molded, the normal saline is infused into the stomach, and the model group is obtained. The second to sixth groups were experimental groups, and the oral liquids prepared in examples 1, 2, 3, 4, and 5 were administered by gavage, respectively. The seventh to ninth groups are positive control groups, and respectively administered with compound preparation of bupleuri radix, radix Angelicae sinensis, radix Paeoniae alba, and ramulus Cinnamomi by intragastric administration; bupleurum, angelica, white peony root, cassia twig, crinum asiaticum compound or bupleurum, angelica, white peony root, cassia twig, pleurotus citrinopileatus compound oral liquid. The single administration dosage is 0.3g/kg calculated by radix bupleuri crude drugs, and the administration is performed for 28 days by intragastric administration for 1 time per day.
The compound formula of the radix bupleuri, the angelica, the white paeony root and the cassia twig and the preparation method are as follows: 66g of bupleurum, 38g of angelica, 38g of white peony root and 24g of cassia twig.
Pulverizing bupleuri radix, radix Angelicae sinensis, radix Paeoniae alba, and ramulus Cinnamomi respectively, sieving with 50 mesh sieve, mixing to obtain crude medicinal materials, decocting with water for 2 times, adding water 7 times the weight of crude medicinal materials for 1 time, decocting for 4 hr, adding water 3 times the weight of crude medicinal materials for 2 times, filtering, mixing water decoctions, concentrating to obtain concentrated solution with relative density of 1.20, standing, cooling, adding ethanol into the concentrated solution to make ethanol volume percentage of 75%, standing overnight at 4 deg.C, filtering to remove insoluble substances, collecting filtrate, distilling under reduced pressure to remove ethanol to obtain refined solution, and concentrating under reduced pressure to obtain fluid extract with relative density of 1.24 at 60 deg.C; adding 12g of beta-cyclodextrin into the fluid extract, adding 0.8 g of polysorbate-80 into each 100 ml of the fluid extract, and stirring uniformly to prepare the oral liquid preparation.
The compound formula of the Chinese thorowax root, the Chinese angelica, the white paeony root, the cassia twig and the Crinum asiaticum and the preparation method thereof are as follows: 66g of bupleurum, 38g of angelica, 38g of white peony root, 24g of cassia twig and 12g of crinum asiaticum.
A. Pulverizing bupleuri radix, radix Angelicae sinensis, radix Paeoniae alba, and ramulus Cinnamomi respectively, sieving with 50 mesh sieve, mixing to obtain crude medicinal materials, decocting with water for 2 times, adding water 7 times the weight of crude medicinal materials for 1 time, decocting for 4 hr, adding water 3 times the weight of crude medicinal materials for 2 times, filtering, mixing water decoctions, concentrating to obtain concentrated solution with relative density of 1.20, standing, cooling, adding ethanol into the concentrated solution to make ethanol volume percentage of 75%, standing overnight at 4 deg.C, filtering to remove insoluble substances, collecting filtrate, distilling under reduced pressure to remove ethanol to obtain refined solution, concentrating under reduced pressure to obtain fluid extract with relative density of 1.24 at 60 deg.C;
B. grinding crinum asiaticum into fine powder according to the prescription amount, adding the fine powder into a volatile oil extractor, adding water into the fine powder according to the proportion that 12 milliliters of water is added into each gram of the fine powder, soaking for 1 hour, extracting by a steam distillation method at the extraction temperature of 75 ℃ for 10 hours, and separating the volatile oil with the relative density of less than 1.0 for later use;
C. b, taking beta-cyclodextrin according to the proportion that 7 g of beta-cyclodextrin is used for each milliliter of volatile oil, adding distilled water to prepare a saturated aqueous solution at the temperature of 50 ℃, slowly dripping the volatile oil obtained in the step B into the saturated aqueous solution of the beta-cyclodextrin under the condition of heat preservation, stirring for 1 hour, and freeze-drying to obtain a beta-cyclodextrin inclusion compound;
D. and D, adding the beta-cyclodextrin inclusion compound obtained in the step C into the fluid extract obtained in the step A, adding 0.8 g of polysorbate-80 into each 100 ml of the fluid extract, and uniformly stirring to prepare the oral liquid preparation.
The compound formula of the bupleurum, the angelica, the white paeony root, the cassia twig and the pleurotus citrinopileatus comprises the following components: 66g of bupleurum, 38g of angelica, 38g of white peony root, 24g of cassia twig and 10g of pleurotus citrinopileatus.
Respectively crushing bupleurum, angelica, white paeony root, cassia twig and pleurotus citrinopileatus according to the prescription amount, sieving with a 50-mesh sieve, mixing to obtain crude medicinal powder, adding water for decocting for 2 times, adding water 7 times the weight of the crude medicinal powder for decocting for 4 hours for the 1 st time, adding water 3 times the weight of the crude medicinal powder for decocting for 2 hours for the 2 nd time, filtering and combining water decoction, concentrating to obtain concentrated solution with the relative density of 1.20, standing and cooling, adding ethanol into the concentrated solution to ensure that the volume percentage of the ethanol is 75 percent, standing overnight at 4 ℃, filtering to remove insoluble substances, collecting filtrate, distilling under reduced pressure to remove the ethanol to obtain refined solution, concentrating the refined solution under reduced pressure to obtain fluid extract with the relative density of 1.24 at 60 ℃; adding 12g of beta-cyclodextrin into the fluid extract, adding 0.8 g of polysorbate-80 into each 100 ml of the fluid extract, and stirring uniformly to prepare the oral liquid preparation.
Third, observe the index
1. The safety index is as follows: during the administration process, the defecation and diet drinking states of animals are observed every day, the heart rate of each group of rats in a quiet state is measured by a rat heart rate measuring instrument (Shanghai Yuyan scientific instruments Co., Ltd.) every 4 days, 3 times are measured in 5 minutes for each rat, and the average value represents the heart rate value of the day.
2. The curative effect index is as follows:
the behavioural characteristics of the rats were determined 24 hours after the last dose using an open field experiment. The bottom surface of the open box is 100 cm multiplied by 100 cm, the height of the square lattices is equally divided into 25, the height of the square lattices is 40 cm, and a camera is arranged on the top cover of the open box and used for observing the movement of a rat. During the experiment, rats were placed in the central grid and observed for the number of times the rats crossed the transverse grid (at least 3 paw-strides) and upright (two forelimbs at least 1 cm from the floor). The time for each rat was measured for 5 min and the number of crossing the bars and erections within 4 min after the measurement was recorded. The number of crossing horizontal grids is used as the score of horizontal movement, and the number of vertical movements is used as the score of vertical movement. Each rat was measured 1 time, after the measurement was completed, the next rat was measured by cleaning the open chamber with alcohol and scrubbing to avoid odor interference.
Data were statistically processed using SPSS 17.0 software. Comparisons between groups were performed using one-way anova and Post hoc test.P<0.05 was considered statistically significant for the differences. The results of the open field experiments in each group of rats are shown in the following table:
compared with the first group and the model group, A: p < 0.01; compared with the seventh group: c: p <0.05, D: p < 0.01.
As can be seen from the results of the horizontal and vertical motor scores of the model rats, the horizontal and vertical motor scores of the second to ninth groups of rats are significantly higher than those of the first group (P < 0.01), which indicates that the compound oral preparation containing radix bupleuri, angelica, radix paeoniae alba and cassia twig has significant improvement effect on the behavioral characteristics of depression rats.
Compared with the seventh group of administration group of compound oral liquid preparation of radix bupleuri, angelica, radix paeoniae alba and cassia twig, the ninth group of administration group of compound oral liquid preparation of radix bupleuri, angelica, radix paeoniae alba, cassia twig and pleurotus citrinopileatus has no obvious improvement on the horizontal exercise score and the vertical exercise score, which indicates that the pleurotus citrinopileatus has no synergistic effect on the compound oral liquid preparation of radix bupleuri, angelica, radix paeoniae alba and cassia twig. The eighth group, namely the administration group of the compound oral liquid preparation of the bupleurum, the angelica, the white paeony root, the cassia twig and the crinum asiaticum has obviously improved horizontal movement score and vertical movement score (P <0.05 or P < 0.01), which indicates that the crinum asiaticum has synergistic effect on the compound oral liquid preparation of the bupleurum, the angelica, the white paeony root and the cassia twig. The horizontal movement score and the vertical movement score of the rats in the second group to the sixth group are both obviously higher than those in the seventh group (P <0.05 or P < 0.01), but the horizontal movement score and the vertical movement score are not obviously different from those in the eighth group, which indicates that the synergistic effect of the crinum asiaticum on the bupleurum, the angelica, the white paeony root and the cassia twig compound is not influenced by the addition of the pleurotus citrinopileatus.
The eighth group of rats, namely 7 rats with loose stool and unformed symptoms and 8 rats with accelerated heart rate, begin from the 16 th day after the first administration, the heart rates of the eighth group of rats are 347-362 times/minute and the heart rates of other groups of rats are 324-341 times/minute, and the symptoms are not improved until the end of the experiment. No other group of rats had the above symptoms. The toxic effect of the bupleurum, the angelica, the white paeony root and the cassia twig is avoided, the addition of the crinum asiaticum probably causes loose stool and accelerated heart rate of rats, and the addition of the pleurotus citrinopileatus inhibits the toxic effect of the crinum asiaticum.
Claims (9)
1. An oral traditional Chinese medicine composition for treating depression is prepared from pharmaceutically acceptable pharmaceutical excipients and the following traditional Chinese medicine raw materials: radix bupleuri, angelica, white peony root, cassia twig, crinum asiaticum and pleurotus citrinopileatus; the traditional Chinese medicine comprises the following raw materials in parts by weight: 21-35 parts of radix bupleuri, 16-20 parts of angelica sinensis, 16-20 parts of radix paeoniae alba, 7-13 parts of cassia twig, 2-7 parts of crinum asiaticum and 2-6 parts of pleurotus citrinopileatus; wherein the bupleuri radix, radix Angelicae sinensis, radix Paeoniae alba, ramulus Cinnamomi, and Pleurotus Citrinopileatus Sing adopt water extraction and ethanol precipitation method to extract ethanol soluble part, and Crinum flower adopts steam distillation method to extract volatile oil component with relative density below 1.0.
2. The oral traditional Chinese medicine composition for treating depression according to claim 1, wherein the traditional Chinese medicine raw materials comprise the following components in parts by weight: 33 parts of bupleurum, 19 parts of angelica, 19 parts of white peony root, 12 parts of cassia twig, 6 parts of crinum asiaticum and 5 parts of pleurotus citrinopileatus.
3. The oral traditional Chinese medicine composition for treating depression according to claim 1, wherein the traditional Chinese medicine raw materials comprise the following components in parts by weight: 30 parts of radix bupleuri, 18 parts of angelica, 18 parts of radix paeoniae alba, 11 parts of cassia twig, 3 parts of crinum asiaticum flower and 4 parts of pleurotus citrinopileatus.
4. The oral traditional Chinese medicine composition for treating depression according to claim 1, wherein the traditional Chinese medicine raw materials comprise the following components in parts by weight: 27 parts of radix bupleuri, 18 parts of angelica, 17 parts of radix paeoniae alba, 9 parts of cassia twig, 5 parts of crinum asiaticum flower and 4 parts of pleurotus citrinopileatus.
5. The oral traditional Chinese medicine composition for treating depression according to claim 1, wherein the traditional Chinese medicine raw materials comprise the following components in parts by weight: 25 parts of bupleurum, 19 parts of angelica, 17 parts of white peony root, 10 parts of cassia twig, 6 parts of crinum asiaticum and 4 parts of pleurotus citrinopileatus.
6. The oral traditional Chinese medicine composition for treating depression according to claim 1, wherein the traditional Chinese medicine raw materials comprise the following components in parts by weight: 22 parts of radix bupleuri, 17 parts of angelica, 18 parts of radix paeoniae alba, 8 parts of cassia twig, 3 parts of crinum asiaticum flower and 3 parts of pleurotus citrinopileatus.
7. A traditional Chinese medicine oral liquid for treating depression is prepared from pharmaceutically acceptable pharmaceutical excipients and the following traditional Chinese medicine raw materials: radix bupleuri, angelica, white peony root, cassia twig, crinum asiaticum and pleurotus citrinopileatus; wherein the Chinese medicinal materials comprise the following raw materials in parts by weight: 21-35 parts of radix bupleuri, 16-20 parts of angelica sinensis, 16-20 parts of radix paeoniae alba, 7-13 parts of cassia twig, 2-7 parts of crinum asiaticum and 2-6 parts of pleurotus citrinopileatus; wherein the bupleurum, the angelica, the white paeony root, the cassia twig and the pleurotus citrinopileatus are extracted by a water extraction and alcohol precipitation method, and the crinum asiaticum is extracted by a steam distillation method to obtain a volatile oil component with the relative density of less than 1.0; the pharmaceutically acceptable pharmaceutic adjuvant comprises beta-cyclodextrin and polysorbate-80.
8. The method for preparing a Chinese medicinal oral liquid for treating depression as claimed in claim 7, comprising the steps of:
A. respectively crushing bupleurum, angelica, white paeony root, cassia twig and pleurotus citrinopileatus according to the formula amount, sieving with a 50-mesh sieve, mixing to obtain medicinal material coarse powder, adding water for decocting for 2 times, adding water with the weight 7 times of the medicinal material coarse powder for decocting for 4 hours for the 1 st time, adding water with the weight 3 times of the medicinal material coarse powder for decocting for 2 hours for the 2 nd time, filtering and combining water decoction, concentrating to obtain a concentrated solution with the relative density of 1.20, standing and cooling, adding ethanol into the concentrated solution to ensure that the volume percentage of the ethanol is 75 percent, standing overnight at 4 ℃, filtering to remove insoluble substances, collecting filtrate, distilling under reduced pressure to remove the ethanol to obtain a refined solution, concentrating the refined solution under reduced pressure to obtain a fluid extract with the relative density of 1.22-;
B. grinding crinum asiaticum into fine powder according to the prescription amount, adding the fine powder into a volatile oil extractor, adding water into the fine powder according to the proportion that 10-13 milliliters of water is added into each gram of the fine powder, soaking for 1 hour, extracting by a steam distillation method at the extraction temperature of 75 ℃ for 8-11 hours, and separating the volatile oil with the relative density of less than 1.0 for later use;
C. b, taking beta-cyclodextrin according to the proportion that 7 g of beta-cyclodextrin is used for each milliliter of volatile oil, adding distilled water to prepare a saturated aqueous solution at the temperature of 50 ℃, slowly dripping the volatile oil obtained in the step B into the saturated aqueous solution of the beta-cyclodextrin under the condition of heat preservation, stirring for 1 hour, and freeze-drying to obtain a beta-cyclodextrin inclusion compound;
D. and D, adding the beta-cyclodextrin inclusion compound obtained in the step C into the fluid extract obtained in the step A, adding polysorbate-80 according to the proportion that 0.8 g of polysorbate-80 is added into each 100 ml of the fluid extract, uniformly stirring, and subpackaging to obtain the product.
9. The method for preparing a Chinese medicinal oral liquid for treating depression according to claim 8, wherein the relative density of the fluid extract in the step A is 1.24; in the step B, 12 ml of water is added into each gram of fine powder, and the extraction time is 10 hours.
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| CN104069171A (en) * | 2014-07-03 | 2014-10-01 | 成都中医药大学 | Antidepressant medicine composition as well as preparation method and application thereof |
| CN105477126A (en) * | 2015-12-30 | 2016-04-13 | 广东药学院 | Traditional Chinese medicine extract composition used for treating depression and preparation method and application thereof |
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| CN104069171A (en) * | 2014-07-03 | 2014-10-01 | 成都中医药大学 | Antidepressant medicine composition as well as preparation method and application thereof |
| CN105477126A (en) * | 2015-12-30 | 2016-04-13 | 广东药学院 | Traditional Chinese medicine extract composition used for treating depression and preparation method and application thereof |
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