CN113713047A - Rhizoma gastrodiae refreshing liquid traditional Chinese medicine composition and preparation method and application thereof - Google Patents
Rhizoma gastrodiae refreshing liquid traditional Chinese medicine composition and preparation method and application thereof Download PDFInfo
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- CN113713047A CN113713047A CN202111059820.4A CN202111059820A CN113713047A CN 113713047 A CN113713047 A CN 113713047A CN 202111059820 A CN202111059820 A CN 202111059820A CN 113713047 A CN113713047 A CN 113713047A
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- A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization
Abstract
The invention relates to a rhizoma gastrodiae refreshing liquid traditional Chinese medicine composition and a preparation method and application thereof. Specifically, the invention relates to a rhizoma gastrodiae refreshing traditional Chinese medicine composition in a liquid form, which is prepared from the following raw material medicines in parts by weight: 200-400 parts of gastrodia elata, 150-250 parts of earthworm, 200-400 parts of rhizoma acori graminei, 150-250 parts of polygala tenuifolia, 50-150 parts of prepared rehmannia root and 50-150 parts of cistanche deserticola. The Chinese medicinal composition also comprises solvent such as water; for example, the liquid Chinese medicinal composition prepared from each 300 parts of rhizoma acori graminei comprises 2000-10000 parts by weight of water. Typically, the Chinese medicinal composition is in the form of an oral liquid preparation. The Chinese medicinal composition can be used for treating or preventing hypomnesis and unresponsiveness, treating or preventing encephalatrophy and treating or preventing cerebral dementia caused by stroke or brain trauma.
Description
Technical Field
The invention belongs to the field of traditional Chinese medicines, relates to a traditional Chinese medicine composition containing gastrodia elata, earthworm, rhizoma acori graminei, polygala tenuifolia, prepared rehmannia root and cistanche, and particularly relates to a liquid gastrodia elata consciousness-restoring traditional Chinese medicine composition containing gastrodia elata, earthworm, rhizoma acori graminei, polygala tenuifolia, prepared rehmannia root and cistanche, a preparation method of the composition and application of the composition.
Background
Brain atrophy, senile dementia and other diseases are one of the diseases of senile brain dysfunction, intelligence deterioration, social activity deterioration and change of personality behavior, and are chronic, progressive and mental deterioration diseases, and one of the worldwide medical problems. The pathology is atrophy of cerebral cortex, is also related to genetic factors, and is characterized by slow onset of disease, overall impairment of cerebral function, intelligent degeneration, and accompanying disorders in memory, its tropism, emotion, thinking and personality, and some may enter severe dementia after four or five years if not actively controlled. The clinical manifestations are slow onset, the earliest manifestations are hypomnesis, forgetting before and after saying, frequent loss of things, dull expression of patients, slow response, dizziness, unstable standing and walking, and slow loss of self-care ability of life. In addition, the above symptoms are also caused by brain parenchymal damage caused by cerebrovascular accidents and traffic accidents. It is worth emphasizing that the number of the patient groups is increasing in real life, and a heavy burden is brought to the society and families.
In the existing medicines, some effects are not obvious; some imported western medicines are high in selling price, and the economic capacity of a patient is hard to bear. Particularly, the existing medicines for treating the central system have large side effects, but the degenerative diseases of the nervous system usually need to be taken for a long time, gastrointestinal tract reaction, postural hypotension, sleep quality reduction, nasal obstruction, dry mouth and other discomfort caused by long-time taking of the medicines further increase the pain of patients.
CN1583031A (CN1257743C, chinese patent application No. CN200410022700.7) discloses a compound gastrodia tuber medicine, its preparation method and application, wherein the medicine is prepared from gastrodia tuber, earthworm, grassleaved sweetflag rhizome, polygala root, prepared rehmannia root and broomrape in a certain weight ratio. It can be prepared into any common oral administration dosage form. The medicine of the present invention has determined curative effect on hypomnesis, reaction retardation, brain atrophy, etc. and may be used in treating cerebral dementia caused by apoplexy and brain trauma. The rhizoma gastrodiae consciousness restoring capsule (Chinese medicine standard Z20027062) developed by the patent is used clinically for many years and is collected and carried by multiple versions of Chinese pharmacopoeia, so that huge social benefits are generated. The content of the rhizoma gastrodiae consciousness restoring capsule is light yellow to brown yellow granules and powder, each granule is filled with 0.4g, and the rhizoma gastrodiae consciousness restoring capsule is fishy in smell, pungent and salty in taste. Has effects in nourishing liver and kidney, dredging meridians, and relieving pain; can be clinically used for treating headache, dizziness, hypomnesis, insomnia, reaction retardation, tinnitus and waist soreness caused by liver and kidney deficiency by 2 granules at a time and 3 times a day.
CN1981852A (Chinese patent application No. CN200610138595.2) discloses a rhizoma Gastrodiae refreshment preparation for treating diseases caused by liver and kidney deficiency and liver wind, its preparation method and quality control method, wherein the rhizoma Gastrodiae refreshment preparation is prepared from rhizoma Gastrodiae, Lumbricus, rhizoma Acori Graminei, cortex et radix Polygalae, radix rehmanniae Preparata, Cistanchis herba or their extracts by weight parts into oral preparations such as pellet, tablet, dispersible tablet, dripping pill, granule, etc.; the product is believed to be mainly used for treating headache, dizziness, hypomnesis, insomnia, reaction retardation, tinnitus, waist soreness and other diseases caused by liver and kidney deficiency and liver wind ascending disturbance, and has reasonable and feasible process, stable and controllable quality and high bioavailability. However, the invention does not substantially improve the inherent quality, such as biological effect, of the gastrodia elata consciousness restoring capsule (Chinese medicine standard Z20027062).
CN1973887A (chinese patent application No. CN200610168076.0) discloses a pharmaceutical composition, which is prepared from rhizoma gastrodiae, earthworm, grassleaf sweelflag rhizome, polygala root, prepared rehmannia root, desertliving cistanche and the like as raw material medicines in a certain proportion, and also discloses a preparation method of the pharmaceutical composition. The invention application which is not granted by a patent also records that the rhizoma gastrodiae consciousness restoring capsule (Chinese medicine standard Z20027062) has obvious treatment effect on headache, dizziness, hypomnesis, insomnia, reaction retardation, tinnitus, waist soreness and other symptoms caused by liver and kidney deficiency and liver wind ascending disturbance. However, the invention does not substantially improve the intrinsic quality, such as biological effect, of the gastrodia elata consciousness restoring capsule (national drug standard Z20027062).
There remains a need in the art for substantial improvements in the intrinsic qualities of gastrodia elata mind-refreshing capsules, such as the biological effects. In addition, the existing solid preparation is disadvantageous in terms of convenience in use thereof from elderly patients who have better compliance in taking liquid preparations such as oral solutions, and thus, there is still a need in the art to develop the gastrodia elata mind-refreshing capsule into a liquid preparation such as an oral liquid preparation.
Disclosure of Invention
The invention aims to further improve the internal quality of the rhizoma gastrodiae consciousness restoring capsule, such as improving the biological effect of the rhizoma gastrodiae consciousness restoring capsule, thereby providing a rhizoma gastrodiae compound medicine with definite curative effect, safe taking and low cost. The invention also aims to provide a preparation method of the medicine. Meanwhile, the invention also aims to provide the application of the medicine in the field of pharmacy. In particular, the invention aims to provide a solid gastrodia elata refreshment traditional Chinese medicine composition and a preparation method and application thereof. Further, the invention aims to provide a new gastrodia elata refreshing preparation for improving the medicine taking compliance of patients, for example, a gastrodia elata refreshing liquid preparation, and a preparation method and application of the new gastrodia elata refreshing preparation. It has been surprisingly found that the rhizoma gastrodiae refreshing traditional Chinese medicine composition prepared by the method of the invention has the beneficial effects of one or more aspects of the invention. The present invention has been completed based on such findings.
Therefore, the invention provides a rhizoma gastrodiae refreshing traditional Chinese medicine composition in a solid form, which is prepared from the following raw material medicines in parts by weight: 200-400 parts of gastrodia elata, 150-250 parts of earthworm, 200-400 parts of rhizoma acori graminei, 150-250 parts of polygala tenuifolia, 50-150 parts of prepared rehmannia root and 50-150 parts of cistanche deserticola.
The traditional Chinese medicine composition according to the first aspect of the invention is prepared from the following raw material medicines in parts by weight: 300 parts of gastrodia elata, 200 parts of earthworm, 300 parts of rhizoma acori graminei, 200 parts of polygala tenuifolia, 100 parts of prepared rehmannia root and 100 parts of cistanche deserticola.
The traditional Chinese medicine composition according to the first aspect of the invention is prepared by a method comprising the following steps:
(1) pulverizing rhizoma Gastrodiae into fine powder, and sieving (for example, 100 mesh sieve);
(2) soaking Lumbricus with ethanol (such as 50-70% ethanol, such as 60% ethanol) for 60-80 hr (such as 72 hr), and filtering to obtain filtrate A;
(3) decocting rhizoma acori graminei, polygala tenuifolia, radix rehmanniae preparata and cistanche in water twice, decocting in water for 1-2 hours (for example, 1.5 hours) for the first time (for example, adding 7-9 times of water, for example, 8 times of water), decocting in water for 0.5-1.5 hours (for example, 1 hour) for the second time (for example, adding 4-7 times of water, for example, 4 times of water), filtering in portions, combining filtrates, concentrating to obtain clear paste with the relative density of 1.10-1.15 (90 ℃), cooling, adding ethanol to ensure that the alcohol content reaches 60%, standing for 24-72 hours (for example, 48 hours), and filtering to obtain filtrate B for later use;
(4) mixing the filtrate A and B, recovering ethanol, adding rhizoma Gastrodiae fine powder, mixing, and drying (e.g. below 80 deg.C) to obtain fine granule.
The traditional Chinese medicine composition according to the first aspect of the invention is used for treating or preventing hypomnesis and unresponsiveness.
The traditional Chinese medicine composition according to the first aspect of the invention is used for treating or preventing brain atrophy and treating or preventing brain dementia caused by stroke or brain trauma.
Further, the second aspect of the present invention provides a method for preparing a Chinese medicinal composition comprising gastrodia elata, earthworm, acorus gramineus soland, polygala tenuifolia, prepared rehmannia root and cistanche salsa, for example, the method for preparing the Chinese medicinal composition of any one of the first aspect of the present invention comprises the following steps:
(1) pulverizing rhizoma Gastrodiae into fine powder, and sieving (for example, 100 mesh sieve);
(2) soaking Lumbricus with ethanol (such as 50-70% ethanol, such as 60% ethanol) for 60-80 hr (such as 72 hr), and filtering to obtain filtrate A;
(3) decocting rhizoma acori graminei, polygala tenuifolia, radix rehmanniae preparata and cistanche in water twice, decocting in water for 1-2 hours (for example, 1.5 hours) for the first time (for example, adding 7-9 times of water, for example, 8 times of water), decocting in water for 0.5-1.5 hours (for example, 1 hour) for the second time (for example, adding 4-7 times of water, for example, 4 times of water), filtering in portions, combining filtrates, concentrating to obtain clear paste with the relative density of 1.10-1.15 (90 ℃), cooling, adding ethanol to ensure that the alcohol content reaches 60%, standing for 24-72 hours (for example, 48 hours), and filtering to obtain filtrate B for later use;
(4) mixing the filtrate A and B, recovering ethanol, adding rhizoma Gastrodiae fine powder, mixing, and drying (e.g. below 80 deg.C) to obtain fine granule.
According to the method of the second aspect of the invention, the traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 200-400 parts of gastrodia elata, 150-250 parts of earthworm, 200-400 parts of rhizoma acori graminei, 150-250 parts of polygala tenuifolia, 50-150 parts of prepared rehmannia root and 50-150 parts of cistanche deserticola.
According to the method of the second aspect of the invention, the traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 300 parts of gastrodia elata, 200 parts of earthworm, 300 parts of rhizoma acori graminei, 200 parts of polygala tenuifolia, 100 parts of prepared rehmannia root and 100 parts of cistanche deserticola.
Furthermore, the third aspect of the present invention provides an application of the traditional Chinese medicine composition of the first aspect of the present invention in preparing a medicine for treating or preventing memory impairment and reaction retardation.
Furthermore, the third aspect of the present invention provides an application of the traditional Chinese medicine composition of the first aspect of the present invention in preparing a medicine for treating or preventing brain atrophy.
Furthermore, the third aspect of the present invention provides an application of the traditional Chinese medicine composition of the first aspect of the present invention in preparing a medicine for treating or preventing dementia caused by stroke or brain trauma.
Furthermore, the invention provides a rhizoma gastrodiae refreshing traditional Chinese medicine composition in a liquid form, which is prepared from the following raw material medicines in parts by weight: 200-400 parts of gastrodia elata, 150-250 parts of earthworm, 200-400 parts of rhizoma acori graminei, 150-250 parts of polygala tenuifolia, 50-150 parts of prepared rehmannia root and 50-150 parts of cistanche deserticola.
The traditional Chinese medicine composition according to the fourth aspect of the invention is prepared from the following raw material medicines in parts by weight: 300 parts of gastrodia elata, 200 parts of earthworm, 300 parts of rhizoma acori graminei, 200 parts of polygala tenuifolia, 100 parts of prepared rehmannia root and 100 parts of cistanche deserticola.
The Chinese medicinal composition according to the fourth aspect of the invention, further comprises a solvent such as water. In one embodiment, the liquid Chinese medicinal composition prepared from each 300 parts of rhizoma acori graminei comprises 2000-10000 parts by weight of water.
The Chinese medicinal composition according to the fourth aspect of the invention, further comprises a bacteriostatic agent (such as sodium benzoate). For example, the concentration of the inhibitor in the liquid form of the Chinese medicinal composition is 0.1-0.3%, such as 0.15-0.25%, such as 0.2%. The traditional Chinese medicine composition according to the fourth aspect of the invention is in the form of an oral liquid preparation.
The traditional Chinese medicine composition according to the fourth aspect of the invention is prepared by the method comprising the following steps:
(1) extracting rhizoma Gastrodiae with 80% ethanol under reflux twice (usually, the amount of ethanol is 0.8-1.2 times of the weight of rhizoma Gastrodiae each time), each time for 1 hr, mixing extractive solutions, and filtering to obtain filtrate T and residue;
(2) soaking Lumbricus with ethanol (such as 50-70% ethanol, such as 60% ethanol) for 60-80 hr (such as 72 hr), and filtering to obtain filtrate A;
(3) decocting rhizoma acori graminei, polygala tenuifolia, radix rehmanniae preparata, cistanche salsa and rhizoma gastrodiae dregs in the step (1) twice by adding water, decocting for 1-2 hours (for example, 1.5 hours) by adding water (for example, adding 7-9 times of water, for example, 8 times of water) for the first time, decocting for 0.5-1.5 hours (for example, 1 hour) by adding water (for example, adding 4-7 times of water, for example, 4 times of water) for the second time, filtering by times, combining filtrates, concentrating to obtain a clear paste with the relative density of 1.10-1.15 (90 ℃), cooling, adding ethanol to ensure that the alcohol content reaches 60%, standing for 24-72 hours (for example, 48 hours), and filtering to obtain a filtrate B for later use;
(4) mixing the filtrate T, the filtrate A and the filtrate B, recovering ethanol until no ethanol smell exists, adding 7.5-12.5 parts by weight of sodium benzoate, mixing uniformly, adding water to 5000 parts by weight, stirring uniformly, filtering, and adding water to 5000 parts by weight to obtain the rhizoma gastrodiae refreshing liquid traditional Chinese medicine composition; optionally subpackaging into oral liquid bottles to obtain 10ml oral liquid per bottle.
The traditional Chinese medicine composition according to the fourth aspect of the invention is used for treating or preventing hypomnesis and unresponsiveness.
The traditional Chinese medicine composition according to the fourth aspect of the invention is used for treating or preventing encephalatrophy, treating or preventing cerebral dementia caused by stroke or cerebral trauma.
Further, the fifth aspect of the present invention provides a method for preparing a Chinese medicinal composition comprising gastrodia elata, earthworm, acorus gramineus soland, polygala tenuifolia, prepared rehmannia root and cistanche salsa, for example, the method for preparing the Chinese medicinal composition of any one of the fourth aspects of the present invention comprises the following steps:
(1) extracting rhizoma Gastrodiae with 80% ethanol under reflux twice (usually, the amount of ethanol is 0.8-1.2 times of the weight of rhizoma Gastrodiae each time), each time for 1 hr, mixing extractive solutions, and filtering to obtain filtrate T and residue;
(2) soaking Lumbricus with ethanol (such as 50-70% ethanol, such as 60% ethanol) for 60-80 hr (such as 72 hr), and filtering to obtain filtrate A;
(3) decocting rhizoma acori graminei, polygala tenuifolia, radix rehmanniae preparata, cistanche salsa and rhizoma gastrodiae dregs in the step (1) twice by adding water, decocting for 1-2 hours (for example, 1.5 hours) by adding water (for example, adding 7-9 times of water, for example, 8 times of water) for the first time, decocting for 0.5-1.5 hours (for example, 1 hour) by adding water (for example, adding 4-7 times of water, for example, 4 times of water) for the second time, filtering by times, combining filtrates, concentrating to obtain a clear paste with the relative density of 1.10-1.15 (90 ℃), cooling, adding ethanol to ensure that the alcohol content reaches 60%, standing for 24-72 hours (for example, 48 hours), and filtering to obtain a filtrate B for later use;
(4) mixing the filtrate T, the filtrate A and the filtrate B, recovering ethanol until no ethanol smell exists, adding 7.5-12.5 parts by weight of sodium benzoate, mixing uniformly, adding water to 5000 parts by weight, stirring uniformly, filtering, and adding water to 5000 parts by weight to obtain the rhizoma gastrodiae refreshing liquid traditional Chinese medicine composition; optionally subpackaging into oral liquid bottles to obtain 10ml oral liquid per bottle.
According to the method of the fifth aspect of the invention, the traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 200-400 parts of gastrodia elata, 150-250 parts of earthworm, 200-400 parts of rhizoma acori graminei, 150-250 parts of polygala tenuifolia, 50-150 parts of prepared rehmannia root and 50-150 parts of cistanche deserticola.
According to the method of the fifth aspect of the invention, the traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 300 parts of gastrodia elata, 200 parts of earthworm, 300 parts of rhizoma acori graminei, 200 parts of polygala tenuifolia, 100 parts of prepared rehmannia root and 100 parts of cistanche deserticola.
Furthermore, the sixth aspect of the present invention provides an application of the traditional Chinese medicine composition according to any one of the fourth aspect of the present invention in preparing a medicine for treating or preventing memory impairment and unresponsiveness.
Furthermore, the sixth aspect of the present invention provides an application of the traditional Chinese medicine composition of any one of the fourth aspects of the present invention in preparing a medicine for treating or preventing brain atrophy.
Furthermore, the sixth aspect of the present invention provides an application of the traditional Chinese medicine composition of any one of the fourth aspect of the present invention in preparing a medicine for treating or preventing dementia caused by stroke or brain trauma.
In the present invention, it has been unexpectedly found that when a Chinese medicinal composition is prepared by extracting Acorus tatarinowii Schott alone, the resulting composition exhibits significantly more excellent biological activity, which has not been taught at all in the prior art. That is, according to any one of the embodiments of any one of the aspects of the present invention, wherein the step (3) of extracting the four components of grassleaf sweelflag rhizome, thinleaf milkwort root-bark, prepared rehmannia root and desertliving cistanche is changed to operate as follows (31) to (33):
(31) decocting polygala tenuifolia, prepared rehmannia root and cistanche salsa twice with water, decocting for 1-2 hours (for example, 1.5 hours) with water (for example, adding 7-9 times of water, for example, 8 times of water) for the first time, decocting for 0.5-1.5 hours (for example, 1 hour) with water (for example, adding 4-7 times of water, for example, 4 times of water) for the second time, filtering for several times, combining filtrates, concentrating to obtain a clear paste with a relative density of 1.10-1.15 (90 ℃), and cooling to obtain a clear paste 1 for later use;
(32) decocting rhizoma acori graminei with water twice, decocting the rhizoma acori graminei with water containing glycine and sodium chloride for 1-2 hours (for example, 1.5 hours) for the first time (for example, adding 7-9 times of water, for example, 8 times of water), decocting the rhizoma acori graminei with water containing glycine and sodium chloride for 0.5-1.5 hours (for example, 1 hour) for the second time (for example, adding 4-7 times of water, for example, 4 times of water), filtering the mixture in multiple times, combining the filtrates, concentrating the combined filtrates to obtain clear paste with the relative density of 1.10-1.15 (90 ℃), and cooling the clear paste to obtain clear paste 2 for later use;
(33) mixing the fluid extract 1 and the fluid extract 2, adding ethanol to make the alcohol content reach 60%, standing for 24-72 hours (for example, 48 hours), and filtering to obtain filtrate B for later use.
Alternatively, according to any one of the embodiments of the present invention, wherein the step (3) of extracting the five herb residues of acorus gramineus, polygala tenuifolia, rehmanniae radix preparata, cistanche deserticola and gastrodia elata is changed to the following steps (31) to (33) for the preparation of the liquid pharmaceutical composition:
(31) decocting polygala tenuifolia, prepared rehmannia root and cistanche salsa twice, adding water into the gastrodia elata dregs in the step (1), decocting for 1-2 hours (for example, 1.5 hours) with water (for example, adding 7-9 times of water, for example, 8 times of water), decocting for 0.5-1.5 hours (for example, 1 hour) with water (for example, adding 4-7 times of water, for example, 4 times of water), filtering for several times, combining filtrates, concentrating to obtain a clear paste with the relative density of 1.10-1.15 (90 ℃), and cooling to obtain a clear paste 1 for later use;
(32) decocting rhizoma acori graminei with water twice, decocting the rhizoma acori graminei with water containing glycine and sodium chloride for 1-2 hours (for example, 1.5 hours) for the first time (for example, adding 7-9 times of water, for example, 8 times of water), decocting the rhizoma acori graminei with water containing glycine and sodium chloride for 0.5-1.5 hours (for example, 1 hour) for the second time (for example, adding 4-7 times of water, for example, 4 times of water), filtering the mixture in multiple times, combining the filtrates, concentrating the combined filtrates to obtain clear paste with the relative density of 1.10-1.15 (90 ℃), and cooling the clear paste to obtain clear paste 2 for later use;
(33) mixing the fluid extract 1 and the fluid extract 2, adding ethanol to make the alcohol content reach 60%, standing for 24-72 hours (for example, 48 hours), and filtering to obtain filtrate B for later use.
In the step (32), the weight ratio of the grassleaf sweelflag rhizome, the glycine and the sodium chloride in the first extraction is 300: 30: 10, the weight ratio of the rhizoma acori graminei, the glycine and the sodium chloride in the second extraction is 300: 15: 5.
the above-mentioned extraction of Acorus gramineus soland alone and the simultaneous addition of both glycine and sodium chloride to the extraction solvent have found that the composition of the chemical substances contributed by Acorus gramineus soland in the resulting extract and composition is changed and the composition exhibits significantly more excellent biological activity.
In the present invention, all percentages used are by weight unless otherwise indicated.
The medicine of the invention is prepared by combining gastrodia elata, earthworm, rhizoma acori graminei, polygala tenuifolia, prepared rehmannia root and cistanche, and the medicine is combined to ensure that the efficacies of the medicines generate synergistic action. Modern pharmacological research shows that the gastrodia elata has the functions of calming the liver, calming the wind, relieving spasm, enriching the blood, strengthening the brain, easing pain, resisting convulsion, inflammation and ischemia and anoxia, reducing vascular resistance, resisting aging, improving learning, memory, enhancing immunity and the like. The earthworm can clear heat, calm fright, dredge collaterals, relieve asthma and promote urination, has the functions of reducing or repairing tissue injury caused by cerebral ischemia, increasing cerebral blood flow, reducing vascular resistance, reducing platelet viscosity and preventing thrombosis, and has good anticoagulation and thrombolysis effects and blood rheology improvement effects. Polygala tenuifolia has effects of tranquilizing mind, improving intelligence, eliminating phlegm, relieving swelling, resisting dementia, protecting brain, and promoting physical strength and intelligence. Rhizoma Acori Graminei has effects of eliminating dampness, promoting appetite, inducing resuscitation, eliminating phlegm, refreshing mind, improving intelligence, tranquilizing mind, resisting convulsion, inducing resuscitation, improving intelligence and nourishing brain. Prepared rehmannia root can nourish yin, enrich blood, replenish essence and fill marrow, and cistanche deserticola can tonify kidney yang and replenish essence and blood. The invention organically combines a plurality of raw materials into a whole, and the components are mutually supported and supplemented in function, thereby generating unexpected treatment effect.
The traditional Chinese medicine composition has the following outstanding advantages: has definite curative effect on hypomnesis, reaction retardation, brain atrophy, and dementia caused by apoplexy or brain trauma. The product is a pure Chinese medicinal preparation, does not contain any component stimulating central nerves, has no toxic or side effect on human bodies, does not damage intestines and stomach, and can be taken for a long time without worry. The raw materials have rich sources, the preparation method is simple, the cost is low, less money can be spent for treating diseases, good news is brought to a plurality of patients, particularly patients with difficult family economy, and the method has good social and economic benefits.
In addition, for the solid compositions and the liquid compositions of examples 5 to 7 of the invention, the acute toxicity of animals is examined by referring to the method carried in CN200410022700.7, and the test process is as follows: each reagent is prepared from 20 ICR mice (Witonglihua), each half of the mice is subjected to intragastric administration three times per day with the maximum volume of 40ml/kg at the maximum concentration of 25% (W/V) of each reagent, and the administration is continuously observed for seven days. None of the 20 animals in each test group died within seven days after administration. The appearance, behavior and activity, mental state, appetite, stool and urine, color, fur, skin color and breathing of the animals are all normal, and abnormal secretion is not generated in the nose, eyes and oral cavity. In example 5, the weight of the animals in the two reagent groups is increased from 18.6 +/-0.4 g to 21.2 +/-0.6 g, and the weight of the animals in any two reagent groups is also increased within a normal range; the drug toxicity was very low, and no LD50 could be detected. The result shows that the medicine of the invention has extremely low toxicity and is safe to take orally.
The active component of the invention can be added with various conventional auxiliary materials required by preparing different dosage forms, such as disintegrating agent, lubricant, adhesive and the like, and prepared into any one of common oral dosage forms, such as pills, powder, tablets, capsules or granules, and the like by a conventional Chinese medicinal preparation method.
Detailed Description
The present invention will be further understood from the specific examples given below. They are not intended to limit the invention. In the following examples, the materials are added or fed in the proportions shown, and the addition or feed amount of the materials can be scaled up or down as required.
Example 1: preparing rhizoma Gastrodiae capsule for refreshing brain
(1) Taking 300 g of gastrodia elata, drying and crushing into 100-mesh fine powder for later use.
(2) Cleaning 200 g of earthworm, drying in the air, grinding, adding 60% ethanol for soaking for 72 hours, filtering, and obtaining filtrate A for later use.
(3) Washing 300 g of rhizoma acori graminei, 200 g of polygala tenuifolia, 100g of prepared rehmannia root and 100g of cistanche deserticola, soaking in 8 times of water for 30 minutes, decocting for 1.5 hours, and filtering; adding 4 times of water, decocting for 1 hr, and filtering; mixing the two filtrates, concentrating to a relative density of 1.10-1.05 (90 ℃), cooling to room temperature, adding ethanol until the ethanol content reaches 60%, standing for 45-50 hours, and filtering to obtain a filtrate B for later use;
(4) combining the filtrate A in the step (2) and the filtrate B in the step (3), and recovering ethanol to obtain liquid medicine for later use; adding the fine powder of the gastrodia elata in the step (1) into the liquid medicine in the step (4), stirring and mixing uniformly, drying at the temperature of below 80 ℃ to obtain dry extract, crushing the dry extract into powder, sieving the powder with a 100-mesh sieve, sterilizing, and encapsulating to obtain 1000 capsules. The recipe preparation method of the present embodiment is essentially the same as the recipe preparation method of the gastrodia elata consciousness restoring capsule carried by the pharmacopoeia, and the content of each capsule weighs 400mg, which is equivalent to that each capsule is prepared from the medicinal materials including 300mg of the acorus gramineus soland.
Example 2: preparing rhizoma Gastrodiae capsule for refreshing brain
The proportion of the raw material medicines is as follows: 300 g of tall gastrodia tuber, 200 g of earthworm, 300 g of grassleaf sweelflag rhizome, 200 g of thinleaf milkwort root-bark, 100g of prepared rehmannia root and 100g of desertliving cistanche.
The preparation method comprises the following steps:
(1) pulverizing rhizoma Gastrodiae into fine powder, and sieving (100 mesh sieve);
(2) soaking Lumbricus with 60% ethanol for 60-80 hr (72 hr), and filtering to obtain filtrate A;
(3) decocting the grass-leaved sweetflag rhizome, the polygala root, the prepared rehmannia root and the cistanche salsa in water twice, adding water (8 times of water) for the first time for 1.5 hours, adding water (4 times of water) for the second time for 1 hour, filtering for times, combining the filtrates, concentrating to obtain clear paste with the relative density of 1.10-1.15 (90 ℃), cooling, adding ethanol to ensure that the alcohol content reaches 60%, standing for 48 hours, and filtering to obtain filtrate B for later use;
(4) mixing the filtrate A and B, recovering ethanol, adding rhizoma Gastrodiae fine powder, mixing, drying at below 80 deg.C to obtain fine granular Chinese medicinal composition, and making into capsule of 1000 granules.
The preparation method of the formula of the embodiment is the same as the preparation method of the gastrodia elata consciousness restoring capsule carried by pharmacopoeia and the commercially available gastrodia elata consciousness restoring capsule (Z20027062), wherein the content of each capsule is 400mg, which is equivalent to that each capsule is prepared from 300mg of medicinal materials including rhizoma acori graminei.
Example 3: preparing rhizoma Gastrodiae capsule for refreshing brain
The proportion of the raw material medicines is as follows: 200 g of gastrodia tuber, 250g of earthworm, 200 g of grassleaf sweelflag rhizome, 250g of thinleaf milkwort root-bark, 50g of prepared rehmannia root and 150 g of desertliving cistanche.
The preparation method comprises the following steps:
(1) pulverizing rhizoma Gastrodiae into fine powder, and sieving (100 mesh sieve);
(2) soaking Lumbricus with ethanol (50% ethanol) for 80 hr, and filtering to obtain filtrate A;
(3) decocting the grass-leaved sweetflag rhizome, the polygala root, the prepared rehmannia root and the cistanche salsa in water twice, adding water (7 times of water) for 2 hours for the first time, adding water (5 times of water) for 1.5 hours for the second time, filtering for several times, combining the filtrates, concentrating to obtain clear paste with the relative density of 1.10-1.15 (90 ℃), cooling, adding ethanol to ensure that the alcohol content reaches 60%, standing for 24 hours, and filtering to obtain filtrate B for later use;
(4) mixing the filtrate A and B, recovering ethanol, adding rhizoma Gastrodiae fine powder, mixing, drying at below 80 deg.C to obtain fine granular Chinese medicinal composition, and making into capsule of 1000 granules.
Example 4: preparing rhizoma Gastrodiae capsule for refreshing brain
The proportion of the raw material medicines is as follows: rhizoma gastrodiae 400 g, earthworm 150 g, grassleaved sweetflag 400 g, polygala root 150 g, prepared rehmannia root 150 g and broomrape 50 g.
The preparation method comprises the following steps:
(1) pulverizing rhizoma Gastrodiae into fine powder, and sieving (100 mesh sieve);
(2) soaking Lumbricus with 70% ethanol for 60 hr, and filtering to obtain filtrate A;
(3) decocting the grass-leaved sweetflag rhizome, the polygala root, the prepared rehmannia root and the cistanche salsa with water twice, adding water (9 times of water) for the first time for 1 hour, adding water (7 times of water) for the second time for 0.5 hour, filtering for several times, combining the filtrates, concentrating to obtain clear paste with the relative density of 1.10-1.15 (90 ℃), cooling, adding ethanol to ensure that the alcohol content reaches 60%, standing for 72 hours, and filtering to obtain filtrate B for later use;
(4) mixing the filtrate A and B, recovering ethanol, adding rhizoma Gastrodiae fine powder, mixing, drying at below 80 deg.C to obtain fine granular Chinese medicinal composition, and making into capsule of 1000 granules.
Example 5: preparing rhizoma Gastrodiae capsule for refreshing brain
The proportion of the raw material medicines is as follows: 300 g of tall gastrodia tuber, 200 g of earthworm, 300 g of grassleaf sweelflag rhizome, 200 g of thinleaf milkwort root-bark, 100g of prepared rehmannia root and 100g of desertliving cistanche.
The preparation method comprises the following steps:
(1) pulverizing rhizoma Gastrodiae into fine powder, and sieving (100 mesh sieve);
(2) soaking Lumbricus with 60% ethanol for 60-80 hr (72 hr), and filtering to obtain filtrate A;
(31) decocting polygala root, prepared rehmannia root and cistanche in water twice, decocting the polygala root, the prepared rehmannia root and the cistanche twice in water for 1.5 hours in the first time, decocting the polygala root, the prepared rehmannia root and the cistanche for 1 hour in the second time in water (8 times of water), filtering the mixture for times, combining the filtrates, concentrating the mixed filtrates to obtain clear paste with the relative density of 1.10-1.15 (90 ℃), and cooling the clear paste to obtain clear paste 1 for later use;
(32) decocting rhizoma acori graminei with water twice, decocting the rhizoma acori graminei with water (8 times of water) containing glycine and sodium chloride for 1.5 hours for the first time, decocting the rhizoma acori graminei with water (4 times of water) containing glycine and sodium chloride for 1 hour for the second time, filtering the mixture by times, combining filtrates, concentrating the filtrate to obtain clear paste with the relative density of 1.10-1.15 (90 ℃), and cooling the clear paste to obtain clear paste 2 for later use; the weight ratio of the grassleaf sweelflag rhizome, the glycine and the sodium chloride in the first extraction is 300: 30: 10, during the second extraction, the weight ratio of the rhizoma acori graminei, the glycine and the sodium chloride is 300: 15: 5;
(33) mixing fluid extract 1 and fluid extract 2, adding ethanol to make ethanol content reach 60%, standing for 48 hr, and filtering to obtain filtrate B;
(4) mixing the filtrate A and B, recovering ethanol, adding rhizoma Gastrodiae fine powder, mixing, drying at below 80 deg.C to obtain fine granular Chinese medicinal composition, and making into capsule of 1000 granules.
The formulation of the herbs in this example is the same as that in example 2, but the preparation method is different, and the content of each capsule is equivalent to that of the herbs containing Acorus gramineus soland 300mg, therefore, even though the weight of the content of each capsule in this example 5 is different from that in example 2, the amounts of the herbs are equivalent, i.e., the two can be characterized by the content of the capsule similar to that of the herbs containing Acorus gramineus soland xxxmg or the Chinese medicinal composition in the form of fine particles when comparing the dosages. The remaining embodiments may be similarly described.
Example 6: preparing rhizoma Gastrodiae capsule for refreshing brain
The proportion of the raw material medicines is as follows: 200 g of gastrodia tuber, 250g of earthworm, 200 g of grassleaf sweelflag rhizome, 250g of thinleaf milkwort root-bark, 50g of prepared rehmannia root and 150 g of desertliving cistanche.
The preparation method comprises the following steps:
(1) pulverizing rhizoma Gastrodiae into fine powder, and sieving (100 mesh sieve);
(2) soaking Lumbricus with ethanol (50% ethanol) for 80 hr, and filtering to obtain filtrate A;
(31) decocting polygala root, prepared rehmannia root and cistanche in water twice, decocting for 2 hours in water (7 times of water) for the first time, decocting for 1.5 hours in water (5 times of water) for the second time, filtering in times, combining filtrates, concentrating to obtain clear paste with relative density of 1.10-1.15 (90 ℃), and cooling to obtain clear paste 1 for later use;
(32) decocting rhizoma acori graminei with water twice, decocting the rhizoma acori graminei with water (7 times of water) containing glycine and sodium chloride for 2 hours for the first time, decocting the rhizoma acori graminei with water (5 times of water) containing glycine and sodium chloride for 1.5 hours for the second time, filtering the rhizoma acori graminei with water in parts by times, combining filtrates, concentrating the combined filtrates to obtain clear paste with the relative density of 1.10-1.15 (90 ℃), and cooling the clear paste to obtain clear paste 2 for later use; the weight ratio of the grassleaf sweelflag rhizome, the glycine and the sodium chloride in the first extraction is 300: 30: 10, during the second extraction, the weight ratio of the rhizoma acori graminei, the glycine and the sodium chloride is 300: 15: 5;
(33) mixing fluid extract 1 and fluid extract 2, adding ethanol to make ethanol content reach 60%, standing for 24 hr, and filtering to obtain filtrate B;
(4) mixing the filtrate A and B, recovering ethanol, adding rhizoma Gastrodiae fine powder, mixing, drying at below 80 deg.C to obtain fine granular Chinese medicinal composition, and making into capsule of 1000 granules.
Example 7: preparing rhizoma Gastrodiae capsule for refreshing brain
The proportion of the raw material medicines is as follows: rhizoma gastrodiae 400 g, earthworm 150 g, grassleaved sweetflag 400 g, polygala root 150 g, prepared rehmannia root 150 g and broomrape 50 g.
The preparation method comprises the following steps:
(1) pulverizing rhizoma Gastrodiae into fine powder, and sieving (100 mesh sieve);
(2) soaking Lumbricus with 70% ethanol for 60 hr, and filtering to obtain filtrate A;
(31) decocting polygala root, prepared rehmannia root and cistanche in water twice, decocting the first time in water (9 times of water) for 1 hour, decocting the second time in water (7 times of water) for 0.5 hour, filtering the decoction by times, combining the filtrates, concentrating the mixed filtrate to obtain clear paste with the relative density of 1.10-1.15 (90 ℃), and cooling the clear paste to obtain clear paste 1 for later use;
(32) decocting rhizoma acori graminei with water twice, decocting the rhizoma acori graminei with water (9 times of water) containing glycine and sodium chloride for 1 hour for the first time, decocting the rhizoma acori graminei with water (7 times of water) containing glycine and sodium chloride for 0.5 hour for the second time, filtering the mixture by times, combining filtrates, concentrating the filtrate to obtain clear paste with the relative density of 1.10-1.15 (90 ℃), and cooling the clear paste to obtain clear paste 2 for later use; the weight ratio of the grassleaf sweelflag rhizome, the glycine and the sodium chloride in the first extraction is 300: 30: 10, during the second extraction, the weight ratio of the rhizoma acori graminei, the glycine and the sodium chloride is 300: 15: 5;
(33) mixing the fluid extract 1 and the fluid extract 2, adding ethanol to make the alcohol content reach 60%, standing for 24-72 hours (for example, 48 hours), and filtering to obtain filtrate B for later use;
(4) mixing the filtrate A and B, recovering ethanol, adding rhizoma Gastrodiae fine powder, mixing, drying at below 80 deg.C to obtain fine granular Chinese medicinal composition, and making into capsule of 1000 granules.
Example 8: preparing rhizoma Gastrodiae capsule for refreshing brain
Referring to the formulation and preparation method of examples 5-7, respectively, except that glycine is not added in step (32), three fine granular Chinese medicinal compositions named as Ex81, Ex82 and Ex83 are prepared, and are encapsulated respectively.
Example 9: preparing rhizoma Gastrodiae capsule for refreshing brain
Referring to the formulation and preparation method of examples 5-7, respectively, except that no sodium chloride is added in step (32), three fine granular Chinese medicinal compositions named as Ex91, Ex92 and Ex93 are prepared, and are encapsulated respectively.
Example 10: preparing rhizoma Gastrodiae capsule for refreshing brain
Referring to the formulation and preparation method of examples 5-7, respectively, except that neither glycine nor sodium chloride was added in step (32), three fine granular Chinese medicinal compositions designated as Ex101, Ex102 and Ex103 were prepared and encapsulated.
Example 11: preparing rhizoma Gastrodiae capsule for refreshing brain
Referring to the formulation and preparation method of examples 2-4, respectively, except that glycine and sodium chloride (weight ratio of rhizoma Acori Tatarinowii, glycine and sodium chloride is 300: 30: 10 in the first extraction and 300: 15: 5 in the second extraction) are added into the water extracted twice by water decoction in step (3), to obtain three fine granular Chinese medicinal compositions named as Ex111, Ex112 and Ex113, which are respectively encapsulated.
Example 12: preparing rhizoma Gastrodiae oral liquid for refreshing brain
The proportion of the raw material medicines is as follows: 300 g of tall gastrodia tuber, 200 g of earthworm, 300 g of grassleaf sweelflag rhizome, 200 g of thinleaf milkwort root-bark, 100g of prepared rehmannia root and 100g of desertliving cistanche.
The preparation method comprises the following steps:
(1) extracting rhizoma Gastrodiae with 80% ethanol under reflux twice, each for 1 hr, mixing extractive solutions, and filtering to obtain filtrate T and residue;
(2) soaking Lumbricus with 60% ethanol for 60-80 hr (72 hr), and filtering to obtain filtrate A;
(3) decocting rhizoma acori graminei, polygala tenuifolia, radix rehmanniae preparata, cistanche deserticola and rhizoma gastrodiae dregs in the step (1) twice by adding water, decocting for 1.5 hours by adding water (8 times of water) for the first time, decocting for 1 hour by adding water (4 times of water) for the second time, filtering for several times, combining the filtrates, concentrating to obtain clear paste with the relative density of 1.10-1.15 (90 ℃), cooling, adding ethanol to ensure that the alcohol content reaches 60%, standing for 48 hours, and filtering to obtain filtrate B for later use;
(4) mixing the filtrate T, the filtrate A and the filtrate B, recovering ethanol until no ethanol smell exists, adding 10g of sodium benzoate, mixing, adding water to 5000ml, stirring, filtering, adding water to 5000ml, to obtain rhizoma Gastrodiae refreshing liquid Chinese medicinal composition, and packaging into oral liquid bottles to obtain 10ml oral liquid per bottle.
Every 5ml of the oral liquid is equivalent to 1 granule of the rhizoma gastrodiae consciousness restoring capsule carried in the pharmacopoeia (namely the commercial rhizoma gastrodiae consciousness restoring capsule (Z20027062)), and every 2 granules of the rhizoma gastrodiae consciousness restoring capsule carried in the pharmacopoeia are equivalent to 10ml of the oral liquid in the embodiment.
Example 13: preparing rhizoma Gastrodiae oral liquid for refreshing brain
The proportion of the raw material medicines is as follows: 200 g of gastrodia tuber, 250g of earthworm, 200 g of grassleaf sweelflag rhizome, 250g of thinleaf milkwort root-bark, 50g of prepared rehmannia root and 150 g of desertliving cistanche.
The preparation method comprises the following steps:
(1) extracting rhizoma Gastrodiae with 80% ethanol under reflux twice, each for 1 hr, mixing extractive solutions, and filtering to obtain filtrate T and residue;
(2) soaking Lumbricus with ethanol (50% ethanol) for 80 hr, and filtering to obtain filtrate A;
(3) decocting rhizoma acori graminei, polygala tenuifolia, radix rehmanniae preparata, cistanche deserticola and rhizoma gastrodiae dregs in the step (1) twice by adding water, decocting for 2 hours by adding water (7 times of water) for the first time, decocting for 1.5 hours by adding water (5 times of water) for the second time, filtering for several times, combining filtrates, concentrating to obtain clear paste with the relative density of 1.10-1.15 (90 ℃), cooling, adding ethanol to ensure that the alcohol content reaches 60%, standing for 24 hours, and filtering to obtain filtrate B for later use;
(4) mixing the filtrate T, the filtrate A and the filtrate B, recovering ethanol until no ethanol smell exists, adding 7.5 g of sodium benzoate, mixing, adding water to 5000ml, stirring, filtering, adding water to 5000ml, to obtain rhizoma Gastrodiae refreshing liquid Chinese medicinal composition, and packaging into oral liquid bottles to obtain 10ml oral liquid per bottle.
Example 14: preparing rhizoma Gastrodiae oral liquid for refreshing brain
The proportion of the raw material medicines is as follows: rhizoma gastrodiae 400 g, earthworm 150 g, grassleaved sweetflag 400 g, polygala root 150 g, prepared rehmannia root 150 g and broomrape 50 g.
The preparation method comprises the following steps:
(1) extracting rhizoma gastrodiae twice by using 80% ethanol under reflux (in each example of the invention, the dosage of the ethanol is usually 0.8-1.2 times of the weight of the rhizoma gastrodiae each time), and each time lasts for 1 hour, combining the extracting solutions, and filtering to obtain filtrate T and dregs for later use;
(2) soaking Lumbricus with 70% ethanol for 60 hr, and filtering to obtain filtrate A;
(3) decocting rhizoma acori graminei, polygala tenuifolia, radix rehmanniae preparata, cistanche deserticola and rhizoma gastrodiae dregs in the step (1) twice by adding water, decocting for 1 hour by adding water (9 times of water) for the first time, decocting for 0.5 hour by adding water (7 times of water) for the second time, filtering for times, combining filtrates, concentrating to obtain clear paste with the relative density of 1.10-1.15 (90 ℃), cooling, adding ethanol to ensure that the alcohol content reaches 60%, standing for 72 hours, and filtering to obtain filtrate B for later use;
(4) mixing the filtrate T, the filtrate A and the filtrate B, recovering ethanol until no ethanol smell exists, adding 12.5 g of sodium benzoate, mixing, adding water to 5000ml (the density of 5000ml liquid medicine in each embodiment is about 1), stirring, filtering, adding water to 5000ml (the density of 5000ml liquid medicine in each embodiment is about 1) to obtain rhizoma Gastrodiae refreshing liquid Chinese medicinal composition, and subpackaging into oral liquid bottles to obtain 10ml oral liquid per bottle.
Example 15: preparing rhizoma Gastrodiae oral liquid for refreshing brain
The proportion of the raw material medicines is as follows: 300 g of tall gastrodia tuber, 200 g of earthworm, 300 g of grassleaf sweelflag rhizome, 200 g of thinleaf milkwort root-bark, 100g of prepared rehmannia root and 100g of desertliving cistanche.
The preparation method comprises the following steps:
(1) extracting rhizoma Gastrodiae with 80% ethanol under reflux twice, each for 1 hr, mixing extractive solutions, and filtering to obtain filtrate T and residue;
(2) soaking Lumbricus with 60% ethanol for 60-80 hr (72 hr), and filtering to obtain filtrate A;
(31) decocting polygala root, prepared rehmannia root, cistanche and gastrodia elata dregs in the step (1) twice by adding water, decocting for 1.5 hours by adding water (8 times of water) for the first time, decocting for 1 hour by adding water (4 times of water) for the second time, filtering for several times, combining filtrates, concentrating to obtain clear paste with the relative density of 1.10-1.15 (90 ℃), and cooling to obtain clear paste 1 for later use;
(32) decocting rhizoma acori graminei with water twice, decocting the rhizoma acori graminei with water (8 times of water) containing glycine and sodium chloride for 1.5 hours for the first time, decocting the rhizoma acori graminei with water (4 times of water) containing glycine and sodium chloride for 1 hour for the second time, filtering the mixture by times, combining filtrates, concentrating the filtrate to obtain clear paste with the relative density of 1.10-1.15 (90 ℃), and cooling the clear paste to obtain clear paste 2 for later use; the weight ratio of the grassleaf sweelflag rhizome, the glycine and the sodium chloride in the first extraction is 300: 30: 10, during the second extraction, the weight ratio of the rhizoma acori graminei, the glycine and the sodium chloride is 300: 15: 5;
(33) mixing fluid extract 1 and fluid extract 2, adding ethanol to make ethanol content reach 60%, standing for 48 hr, and filtering to obtain filtrate B;
(4) mixing the filtrate T, the filtrate A and the filtrate B, recovering ethanol until no ethanol smell exists, adding 10g of sodium benzoate, mixing uniformly (the weight of the material is about 220g, and the weight of the material in other examples is within the range of 200-250 g), adding water to 5000ml, stirring uniformly, filtering, adding water to 5000ml to obtain the rhizoma gastrodiae refreshing liquid traditional Chinese medicine composition, and subpackaging the rhizoma gastrodiae refreshing liquid traditional Chinese medicine composition into oral liquid bottles to obtain 10ml of oral liquid per bottle.
The formula of the medicinal materials in the embodiment is the same as that in the embodiment 12, but the preparation method is different, and finally, every 5ml of oral liquid is prepared from the medicinal materials containing 300mg of rhizoma acori graminei. The various liquid compositions, when compared to each other in dosage, can be characterized as liquid compositions or oral liquids similar to "equivalent to" made from a medicinal material comprising Acorus gramineus xxxmg ". The remaining embodiments may be similarly described.
Example 16: preparing rhizoma Gastrodiae oral liquid for refreshing brain
The proportion of the raw material medicines is as follows: 200 g of gastrodia tuber, 250g of earthworm, 200 g of grassleaf sweelflag rhizome, 250g of thinleaf milkwort root-bark, 50g of prepared rehmannia root and 150 g of desertliving cistanche.
The preparation method comprises the following steps:
(1) extracting rhizoma Gastrodiae with 80% ethanol under reflux twice, each for 1 hr, mixing extractive solutions, and filtering to obtain filtrate T and residue;
(2) soaking Lumbricus with ethanol (50% ethanol) for 80 hr, and filtering to obtain filtrate A;
(31) decocting polygala root, prepared rehmannia root, cistanche and gastrodia elata dregs in the step (1) twice by adding water, decocting for 2 hours by adding water (7 times of water) for the first time, decocting for 1.5 hours by adding water (5 times of water) for the second time, filtering for several times, combining filtrates, concentrating to obtain clear paste with the relative density of 1.10-1.15 (90 ℃), and cooling to obtain clear paste 1 for later use;
(32) decocting rhizoma acori graminei with water twice, decocting the rhizoma acori graminei with water (7 times of water) containing glycine and sodium chloride for 2 hours for the first time, decocting the rhizoma acori graminei with water (5 times of water) containing glycine and sodium chloride for 1.5 hours for the second time, filtering the rhizoma acori graminei with water in parts by times, combining filtrates, concentrating the combined filtrates to obtain clear paste with the relative density of 1.10-1.15 (90 ℃), and cooling the clear paste to obtain clear paste 2 for later use; the weight ratio of the grassleaf sweelflag rhizome, the glycine and the sodium chloride in the first extraction is 300: 30: 10, during the second extraction, the weight ratio of the rhizoma acori graminei, the glycine and the sodium chloride is 300: 15: 5;
(33) mixing fluid extract 1 and fluid extract 2, adding ethanol to make ethanol content reach 60%, standing for 24 hr, and filtering to obtain filtrate B;
(4) mixing the filtrate T, the filtrate A and the filtrate B, recovering ethanol until no ethanol smell exists, adding 7.5 g of sodium benzoate, mixing, adding water to 5000ml, stirring, filtering, adding water to 5000ml, to obtain rhizoma Gastrodiae refreshing liquid Chinese medicinal composition, and packaging into oral liquid bottles to obtain 10ml oral liquid per bottle.
Example 17: preparing rhizoma Gastrodiae oral liquid for refreshing brain
The proportion of the raw material medicines is as follows: rhizoma gastrodiae 400 g, earthworm 150 g, grassleaved sweetflag 400 g, polygala root 150 g, prepared rehmannia root 150 g and broomrape 50 g.
The preparation method comprises the following steps:
(1) extracting rhizoma Gastrodiae with 80% ethanol under reflux twice, each for 1 hr, mixing extractive solutions, and filtering to obtain filtrate T and residue;
(2) soaking Lumbricus with 70% ethanol for 60 hr, and filtering to obtain filtrate A;
(31) decocting polygala root, prepared rehmannia root, cistanche and gastrodia elata dregs in the step (1) twice by adding water, decocting for 1 hour by adding water (9 times of water) for the first time, decocting for 0.5 hour by adding water (7 times of water) for the second time, filtering for several times, combining filtrates, concentrating to obtain clear paste with the relative density of 1.10-1.15 (90 ℃), and cooling to obtain clear paste 1 for later use;
(32) decocting rhizoma acori graminei with water twice, decocting the rhizoma acori graminei with water (9 times of water) containing glycine and sodium chloride for 1 hour for the first time, decocting the rhizoma acori graminei with water (7 times of water) containing glycine and sodium chloride for 0.5 hour for the second time, filtering the mixture by times, combining filtrates, concentrating the filtrate to obtain clear paste with the relative density of 1.10-1.15 (90 ℃), and cooling the clear paste to obtain clear paste 2 for later use; the weight ratio of the grassleaf sweelflag rhizome, the glycine and the sodium chloride in the first extraction is 300: 30: 10, during the second extraction, the weight ratio of the rhizoma acori graminei, the glycine and the sodium chloride is 300: 15: 5;
(33) mixing the fluid extract 1 and the fluid extract 2, adding ethanol to make the alcohol content reach 60%, standing for 24-72 hours (for example, 48 hours), and filtering to obtain filtrate B for later use;
(4) mixing the filtrate T, the filtrate A and the filtrate B, recovering ethanol until no ethanol smell exists, adding 12.5 g of sodium benzoate, mixing, adding water to 5000ml, stirring, filtering, adding water to 5000ml, to obtain rhizoma Gastrodiae refreshing liquid Chinese medicinal composition, and packaging into oral liquid bottles to obtain 10ml oral liquid per bottle.
Example 18: preparing rhizoma Gastrodiae oral liquid for refreshing brain
Referring to the formulation and preparation method of examples 15-17, respectively, except that glycine was not added in step (32), three oral liquids, which can be called Ex181, Ex182, Ex183, were prepared.
Example 19: preparing rhizoma Gastrodiae oral liquid for refreshing brain
Referring to the formulation and preparation method of examples 15-17, respectively, except that no sodium chloride was added in step (32), three oral liquids, which can be called Ex191, Ex192, and Ex193, respectively, were prepared.
Example 20: preparing rhizoma Gastrodiae oral liquid for refreshing brain
Referring to the formulation and preparation method of examples 15-17, respectively, except that neither glycine nor sodium chloride was added in step (32), three oral liquids, which may be called Ex201, Ex202, and Ex203, were prepared.
Example 21: preparing rhizoma Gastrodiae oral liquid for refreshing brain
Referring to the formulation and preparation method of examples 12-14, respectively, except that glycine and sodium chloride (weight ratio of rhizoma Acori Tatarinowii, glycine and sodium chloride is 300: 30: 10 in the first extraction and 300: 15: 5 in the second extraction) are added into the water extracted by twice water decoction in step (3), and three oral liquids named as Ex211, Ex212 and Ex213 are prepared respectively.
Formulation example 1: preparation of gastrodia tuber refreshment tablet
The fine granular traditional Chinese medicine composition obtained by the method of the embodiment 2, 50g of starch, 25g of microcrystalline cellulose and 3 g of magnesium stearate are uniformly mixed and pressed into tablets on a tablet press, and the weight of each tablet is equivalent to that of the tablet containing 150mg of gastrodia elata medicinal material.
The fine granular traditional Chinese medicine composition obtained by the method of the embodiment 2, 30 g of dextrin, 25g of cane sugar, 2g of talcum powder and 2g of magnesium stearate are uniformly mixed and pressed into tablets on a tablet press, and the weight of each tablet is equivalent to that of the tablet containing 150mg of gastrodia elata medicinal material.
The fine granular traditional Chinese medicine composition obtained by the method of example 5, 50g of starch, 25g of microcrystalline cellulose and 3 g of magnesium stearate are uniformly mixed and pressed into tablets on a tablet press, and the weight of each tablet is equivalent to that of the tablet containing 150mg of gastrodia elata medicinal material.
The fine granular traditional Chinese medicine composition obtained by the method of example 5, 30 g of dextrin, 25g of sucrose, 2g of talcum powder and 2g of magnesium stearate are uniformly mixed and pressed into tablets on a tablet press, and the weight of each tablet is equivalent to that of the tablet containing 150mg of gastrodia elata medicinal material.
Preparation example 2: preparation of gastrodia tuber refreshment pill
The fine granular traditional Chinese medicine composition obtained by the method of the embodiment 2 is crushed into fine powder, and pills are prepared by a pill making method, wherein the weight of each pill is equivalent to that of the pill containing 150mg of gastrodia elata medicinal material.
The fine granular traditional Chinese medicine composition obtained by the method of example 5 is crushed into fine powder, and pills are prepared by a pill making method, wherein the weight of each pill is equivalent to that of the pill containing 150mg of gastrodia elata medicinal material.
Preparation example 3: preparation of rhizoma gastrodiae refreshing granules
The fine granular traditional Chinese medicine composition obtained by the method of the embodiment 2 and 2500 g of cane sugar are crushed into fine powder, the fine powder is granulated by water, dried and subpackaged into aluminum-plastic composite film bags, and the weight of each bag is equivalent to that of a gastrodia elata medicinal material containing 300 mg.
The fine granular traditional Chinese medicine composition obtained by the method of the embodiment 2, 2000 g of cane sugar and 2.5 g of sucralose are crushed into fine powder, the fine powder is granulated by water, dried and subpackaged into aluminum-plastic composite film bags, and the weight of each bag is equivalent to that of the gastrodia elata containing 300 mg.
The fine granular traditional Chinese medicine composition obtained by the method of example 5 and 2500 g of cane sugar are crushed into fine powder, the fine powder is granulated by water, dried and subpackaged into aluminum-plastic composite film bags, and the weight of each bag is equivalent to that of a gastrodia elata medicinal material containing 300 mg.
The fine granular traditional Chinese medicine composition obtained by the method of the embodiment 5, 2000 g of cane sugar and 2.5 g of sucralose are crushed into fine powder, the fine powder is granulated by water, dried and subpackaged into aluminum-plastic composite film bags, and the weight of each bag is equivalent to that of the gastrodia elata containing 300 mg.
Preparation example 4: preparation of gastrodia tuber refreshment powder
Mixing the fine granular traditional Chinese medicine composition obtained by the method of the embodiment 2, 1500 g of cane sugar and 5g of micro silica gel powder, crushing the mixture into superfine powder, and subpackaging the superfine powder into aluminum-plastic composite film bags, wherein the weight of each bag is equivalent to that of a gastrodia elata medicinal material of 300 mg.
Mixing the fine granular traditional Chinese medicine composition obtained by the method of the embodiment 2, 1000 g of cane sugar, 2.5 g of sucralose and 5g of superfine silica gel powder, crushing into superfine powder, and subpackaging into aluminum-plastic composite film bags, wherein the weight of each bag is equivalent to that of a gastrodia elata medicinal material of 300 mg.
Mixing the fine granular traditional Chinese medicine composition obtained by the method of the embodiment 5, 1500 g of cane sugar and 5g of micro silica gel powder, crushing the mixture into superfine powder, and subpackaging the superfine powder into aluminum-plastic composite film bags, wherein the weight of each bag is equivalent to that of a gastrodia elata medicinal material of 300 mg.
Mixing the fine granular traditional Chinese medicine composition obtained by the method of the embodiment 5, 1000 g of cane sugar, 2.5 g of sucralose and 5g of superfine silica gel powder, crushing into superfine powder, and subpackaging into aluminum-plastic composite film bags, wherein the weight of each bag is equivalent to that of a gastrodia elata medicinal material of 300 mg.
Test example 1 a: determining the chemical composition of Acorus tatarinowii Schott extract
The extraction rate of typical chemical substances in the extract related to the acorus gramineus is determined by using HPLC by referring to a method of a small dew literature (small dew, and the like, HPLC fingerprint chromatogram research of an oil-water-removed decoction of the acorus gramineus, new traditional Chinese medicine and clinical pharmacology, 2014, 25 (3): 323-:
chromatographic conditions are as follows: octadecylsilane chemically bonded silica is used as a filler (Agilent C18 chromatographic column, 250mm multiplied by 4.6mm, 5 μm); mobile phase: methanol-water, linear gradient elution, elution procedure: methanol is 4% → 10% during 0 → 20min, 10% → 80% during 20 → 45min, 80% → 4% during 50 → 60min, and 4% during 60 → 63 min; the sample volume is 20 mu L; the flow rate is 1.0 mL/min; the detection wavelength is 270 nm; the column temperature is 30 ℃;
preparation of a test solution: taking a proper amount of fine particles obtained by drying below 80 ℃ in examples 1-11 respectively, grinding into superfine powder, precisely weighing, adding water to dilute until each 1ml of the fine particles contains liquid equivalent to 20mg of the rhizoma acori graminei medicinal material, placing the fine particles in a microwave instrument for ultrasonic treatment for 10min, filtering with a 0.22 mu m microporous membrane, and taking the subsequent filtrate as a sample solution;
example 5 the chromatographic results of the sample show that a considerable peak is presented at 17.042min, which corresponds to the No. 8 peak of the Chenopodium album, and the No. 8 peak is taken as a reference peak (the relative retention time is recorded as 1), and three larger chromatographic peaks appear at 0.1432, 0.4841 and 2.3687 which respectively correspond to the No. 1, 5 and 14 peaks of the Chenopodium album; the samples of the other examples also exhibited typical peak number 8 at 17.04, and typical peak numbers 1, 5, 14 at RRTs of 0.143, 0.484, 2.369;
for each sample, the quotient obtained by dividing the sum of the four peak areas of peaks 1, 5, 8 and 14 by the weight (μ g) of the rhizoma acori graminei drug converted in the sample volume of 20 μ L (which can be referred to as a four-peak quotient in the present invention and reflects the extraction efficiency of the chemical components of the rhizoma acori graminei after the preparation process treatment) is calculated, and the result is:
the quotient of the four peaks of the sample in example 5 is 1574.1 (the sum of the four peak areas is 651046, the amount of the sample of 20. mu.L is equivalent to the weight of the rhizoma acori graminei medicinal material of 413.6. mu.g), the quotient of the four peaks of the sample in example 6 is 1589.3, the quotient of the four peaks of the sample in example 7 is 1536.8,
the four-peak quotient of the four samples of examples 1-4, the three samples of example 8 and the three samples of example 10 are all in the range of 306-341, for example, the four-peak quotient of the sample of example 2 is 316.4,
the four-peak quotient of the three samples in example 9 and the three samples in example 11 is in the range of 393-436, for example, the four-peak quotient of the Ex111 sample is 403.7. Therefore, the compositions prepared by the methods of examples 5 to 7 have a great difference of 3 to 4 times in the content of chemical substances contributed by Acorus gramineus soland from the compositions obtained by the other methods, and the difference may cause the difference in biological activity.
In addition, using the HPLC method described above, each of the fluid extracts 2 obtained in step (32) of examples 5 to 10 was measured, and the quotient obtained by dividing the sum of the four peak areas of peaks No. 1, 5, 8, and 14 of each fluid extract by the weight (μ g) of the tatarinow sweetflag rhizome drug converted in the amount of 20 μ L of the sample (which may be referred to as a four-peak quotient in the present invention, which reflects the extraction efficiency of the chemical components of tatarinow sweetflag rhizome after undergoing the preparation process treatment) was calculated, as a result:
the quotient of the four peaks of the sample in example 5 is 1813.2, the quotient of the four peaks of the sample in example 6 is 1861.4, the quotient of the four peaks of the sample in example 7 is 1786.3,
the quadripeak quotient of the three samples in example 8 and the three samples in example 10 is in the range of 442-487, for example, the quadripeak quotient of the sample in example 81 is 457.2,
the example 9 three samples all have the four-peak quotient in the range of 515-532, for example, the four-peak quotient of the Ex91 sample is 524.1. Therefore, the typical chemical substance content of the rhizoma acori graminei in the fluid extract 2 prepared by the methods in the examples 5 to 7 is greatly different from that of the fluid extract obtained by the other methods by 3 to 4 times, and the result is in accordance with the measurement result of the composition.
Test example 1 b: determining the chemical composition of Acorus tatarinowii Schott extract
As shown in test example 1a, the extraction rate of typical chemical substances in the extract related to Acorus gramineus soland was measured using HPLC by referring to the method of the Chenopodium album reference.
Preparation of a test solution: precisely measuring appropriate amount of the oral liquid obtained in examples 12-21, diluting with water to obtain a solution containing 20mg of rhizoma Acori Graminei per 1ml, filtering with 0.22 μm microporous membrane, and collecting the filtrate as sample solution;
example 15 the chromatographic results of the samples show that a considerable peak is presented at 17.073min, which corresponds to the No. 8 peak of the Chenopodium album, and the No. 8 peak is taken as a reference peak (the relative retention time is recorded as 1), and three larger chromatographic peaks appear at 0.1424, 0.4847 and 2.3675 which correspond to the No. 1, 5 and 14 peaks of the Chenopodium album; the samples of the other examples also all present typical peak No. 8 at 17.07, and typical peak nos. 1, 5, 14 at RRT of 0.143, 0.485, 2.368;
for each sample, the quotient obtained by dividing the sum of the four peak areas of peaks 1, 5, 8 and 14 by the weight (μ g) of the rhizoma acori graminei drug converted in the sample volume of 20 μ L (which can be referred to as a four-peak quotient in the present invention and reflects the extraction efficiency of the chemical components of the rhizoma acori graminei after the preparation process treatment) is calculated, and the result is:
the quotient of the four peaks of the sample in example 15 is 1642.2 (the sum of the four peak areas is 665584, the amount of the sample of 20. mu.L is equivalent to the weight of the Acorus tatarinowii Schott medicinal material of 405.3. mu.g), the quotient of the four peaks of the sample in example 16 is 1628.7, the quotient of the four peaks of the sample in example 17 is 1683.4,
the four-peak quotient of the four samples of examples 12 to 14, the three samples of example 18 and the three samples of example 20 are all in the range of 357 to 384, for example, the four-peak quotient of the sample of example 12 is 374.2,
the example 19 three samples have the four-peak quotient within the range of 417-442, for example, the four-peak quotient of the Ex191 sample is 431.2. It can be seen that the compositions prepared by the methods of examples 15 to 17 have a great difference of 3 to 4 times in the content of the chemical substances contributed by Acorus gramineus soland from the compositions obtained by the other methods, and the difference may result in a difference in biological activity.
In addition, using the HPLC method described above, each of the fluid extracts 2 obtained in step (32) of examples 15 to 20 was measured, and the quotient obtained by dividing the sum of the four peak areas of peaks No. 1, 5, 8, and 14 of each fluid extract by the weight (μ g) of the tatarinow sweetflag rhizome drug converted in the amount of 20 μ L of the sample (which may be referred to as a four-peak quotient in the present invention, which reflects the extraction efficiency of the chemical components of tatarinow sweetflag rhizome after undergoing the preparation process treatment) was calculated, as a result:
the quotient of the four peaks of the sample in example 15 is 1937.3, the quotient of the four peaks of the sample in example 16 is 1953.6, the quotient of the four peaks of the sample in example 17 is 1913.6,
the quotient of the four peaks of the three samples in example 18 and the three samples in example 20 are both in the range of 462-493, for example, the quotient of the four peaks of the sample in example 181 is 481.2,
the example 19 three samples all have the four-peak quotient in the range of 537 to 556, for example, the Ex191 sample has the four-peak quotient of 546.7. Therefore, the typical chemical substance content of the grass-leaved sweetflag rhizome in the clear paste 2 prepared by the methods in examples 15 to 17 is greatly different from that of the clear paste obtained by the other methods by 3 to 4 times, and the result is in accordance with the measurement result of the composition.
Test example 2: hypnotic effect of composition
The hypnotic effect of the composition is investigated by referring to a Chenpeng literature (Chenpeng, et al, research on sedative-hypnotic effect of a gastrodia elata refreshing capsule, and a Yunnan traditional Chinese medicine journal 2007, 28(1): 40-41).
Animals: ICR mice, male with a weight of 18-22 g, the laboratory animal center of Yunnan university (Wittingle). The medicine and the used reagent reference documents are purchased from the market (the pill for tranquilization and heart tonifying is produced in the same benevolence hall, and the compound salvia miltiorrhiza dripping pill is produced in Tianjin Tianshi power). Four gastrodia elata consciousness-restoring capsules of example 2, example 5, example Ex101 and example Ex111 were dissolved/suspended in physiological saline before the experiment. Four rhizoma Gastrodiae refreshing oral liquids of example 12, example 15, example Ex201, and example Ex211 (using them to test the mixture obtained after adding sodium benzoate in step (4), and diluting according to the designed dose) were also tested.
1. Effect on pentobarbital sodium induced sleep in mice
The mice are randomly divided into 10 groups, each group comprises 10, each group comprises four rhizoma gastrodiae refreshing capsules (each kg of animal weight is given with 1.5g of capsule content prepared from rhizoma acori graminei, for example, each kg of animal weight is given with 5 or 2g of example 2 capsules), each group comprises four rhizoma gastrodiae refreshing oral liquids (each kg of animal weight is given with 1.5g of oral liquid prepared from rhizoma acori graminei), each group comprises 2g/kg of mind tranquilizing and heart tonifying pills and normal saline.
The animals of each group were continuously gavaged for 5 days at a dose concentration of 0.2ml/10g body weight, 30min after the last dose, pentobarbital sodium 32mg/kg was intraperitoneally injected to each group, the number of mice with the disappearance of positive reflex for more than 1min was recorded, and the data was statistically processed by X2 test line.
As shown in the table below, the gastrodia elata consciousness-restoring capsules and the mind-tranquilizing and heart-nourishing pills can change the disappearance of the righting reflex of the mice, the capsules in example 5 are obviously better than the capsules in example 2, and the oral liquid in example 15 is obviously better than the oral liquid in example 12.
Table: influence of rhizoma Gastrodiae capsule/oral liquid on sleep induction of pentobarbital sodium in mice (x + -s, n ═ 10)
P <0.01 compared to saline group; compared to the capsule group of example 5, # p < 0.05; in comparison to the oral liquid group of example 15,% p < 0.05.
2. Effect of sodium pentobarbital on sleep time
The mice are randomly divided into 10 groups, 10 in each group, four rhizoma gastrodiae consciousness-restoring capsules in each group (the weight of each kg of animal is given with 1.5g of capsule content made of rhizoma acori graminei, for example, 5 or 2g of example 2 capsule in each kg of animal), four rhizoma gastrodiae consciousness-restoring oral liquids in each group (the weight of each kg of animal is given with 1.5g of oral liquid made of rhizoma acori graminei in each day), 2g/kg of mind-tranquilizing and heart-tonifying pills and normal saline. And (3) continuously performing intragastric administration for 5d at the administration concentration of 0.2ml/10g of body weight for each group of animals, injecting 50mg/kg of sodium pentobarbital into the abdominal cavity 30min after the last administration, taking the disappearance of righting reflex as sleep-in time, and taking the disappearance of righting reflex to recovery time as sleep duration.
As shown in the table below, the tall gastrodia tuber consciousness-restoring capsules and the mind-tranquilizing and heart-nourishing pills can prolong the sleep time of mice caused by the sodium pentobarbital, and the capsules in the example 5 are obviously better than the capsules in the example 2, and the oral liquid in the example 15 is obviously better than the oral liquid in the example 12.
Table: influence of rhizoma Gastrodiae capsule/oral liquid on sleep time of pentobarbital sodium (x + -s, n ═ 10)
| Group of | Sleep time(s) |
| Physiological saline | 233±52 |
| EXAMPLE 2 capsules | 363±71**## |
| EXAMPLE Ex101 Capsule | 348±59**## |
| EXAMPLE Ex111 Capsule | 411±103**## |
| EXAMPLE 5 capsules | 638±87** |
| EXAMPLE 12 oral liquid | 377±92**％％ |
| Example Ex201 oral liquid | 361±85**％％ |
| Example Ex211 oral liquid | 424±78**％％ |
| Example 15 oral liquid | 656±96** |
| Sedative and heart-tonifying pill | 614±96** |
P <0.01 compared to saline group; compared to the capsule group of example 5, # # p < 0.01; in comparison to the oral liquid group of example 15,%% p < 0.01.
The results show that the gastrodia elata consciousness restoring capsule and the gastrodia elata consciousness restoring oral liquid can prolong the sleep time and have excellent hypnotic effect.
Test example 3: the composition has effects in improving learning and memory
The effect of the composition for enhancing the learning and memory functions is examined by referring to a Chenpeng literature (Chenpeng, etc., the influence and mechanism research of the rhizoma gastrodiae consciousness-restoring capsule on the learning and memory functions, the Kunming medical college, 2006 (5): 36-42).
Animals: SD rats, male with a weight of 180-210 g, the university of Yunnan laboratory animal center (Wittinglewa). The drug and the reference of the reagent are purchased from the market (nimodipine tablets are produced by Bayer company, and scopolamine hydrobromide injection is produced by Shanghai Poa). The full-automatic enzyme labeling instrument is Multiskan Skyhigh brand. Other test equipment or reagent agents are all conventionally commercially available.
Four rhizoma gastrodiae consciousness restoring capsules of example 2, example 5, example Ex101 and example Ex111 are dissolved/suspended by normal saline before experiment; four rhizoma gastrodiae refreshing oral liquids of example 12, example 15, example Ex201 and example Ex211 (tested using the mixture obtained after adding sodium benzoate in step (4) and diluted according to the designed dose). When various reagents are dispensed, rats are subjected to intragastric administration with the volume of liquid medicine of 1ml/100g, normal control groups and model control groups are subjected to intragastric administration with equal-volume normal saline, and animals in each group are subjected to intragastric administration for 2 times every day for 15 days continuously. The animals in each group are trained and tested for learning and memory function after the last administration for 1 h.
SD rats were randomly divided into 10 groups of 10 animals each, i.e.: normal control group, model group, rhizoma gastrodiae consciousness restoring capsule group (rhizoma acori graminei 0.45g/kg) in example 2, rhizoma gastrodiae consciousness restoring capsule group (rhizoma acori graminei 0.45g/kg) in example 5, rhizoma gastrodiae consciousness restoring capsule group (rhizoma acori graminei 0.45g/kg) in example Ex101, rhizoma gastrodiae consciousness restoring capsule group (rhizoma acori graminei 0.45g/kg) in example Ex111, rhizoma gastrodiae consciousness restoring capsule group (rhizoma acori graminei 0.45g/kg) in example 12, rhizoma gastrodiae consciousness restoring oral liquid group (rhizoma acori graminei 0.45g/kg) in example 15, rhizoma gastrodiae consciousness restoring oral liquid group (rhizoma acori graminei 0.45g/kg) in example Ex201, rhizoma gastrodiae consciousness restoring oral liquid group (rhizoma acori graminei 0.45g/kg) in example Ex211, rhizoma gastrodiae consciousness restoring oral liquid group (rhizoma acori graminei 0.45g/kg) in example 211 and nimodipine tablet positive control group (rat dose is 0.025 g/kg). The four rhizoma gastrodiae consciousness restoring capsules and the four rhizoma gastrodiae consciousness restoring oral liquids are respectively taken as a group, wherein the content of the capsule or the oral liquid prepared from the rhizoma acori graminei 0.45g is taken every day per kg of animal weight, for example, the capsule in the example 2 is taken as 1.5 grains or 0.6g per kg of animal weight.
Animal obscuration was performed according to Chenpeng literature. Statistical treatment is carried out by adopting an SPSS19.0 statistical software package, experimental data are expressed by mean +/-standard deviation (x +/-s), single-factor variance analysis and q test are adopted for pairwise comparison among mean groups of each sample, and the statistical significance is achieved when the p value is smaller than 0.05. The specific test methods and results are as follows.
1. Influence on rat memory acquisition disorder caused by scopolamine
Rats are trained after the last administration for 1h, a model group and an administration group 20min before the training are injected with scopolamine hydrobromide 3mg/kg in an intraperitoneal mode at the weight of 1mL/100g and normal control groups are injected with physiological saline with the same volume in an intraperitoneal mode at the weight of 1mL/100g respectively, and the testing is carried out again after 24h, and the results are shown in the following table, which shows that the composition provided by the invention has an excellent memory improvement effect.
Table: influence of rhizoma Gastrodiae capsule/oral liquid on rat memory acquisition disorder caused by scopolamine (x + -s, n ═ 10)
P <0.01 compared to model group; compared to the capsules of example 5, # P < 0.05; in comparison to the oral liquid of example 15,% P < 0.05.
2. Influence on rat memory reproduction disorder caused by 40% ethanol
Rats in each group were trained 1h after the last dose and retested 24h later. The model group and the administration group are respectively perfused with 40% ethanol 1mL/100g weight 30min before the test, and normal control group is perfused with normal saline with equal volume. The results are shown in the following table, which shows that the composition of the present invention exhibits excellent memory improving effect.
Table: influence of rhizoma Gastrodiae capsule/oral liquid on rat memory reproduction disorder caused by 40% ethanol (x + -s, n ═ 10)
| Group of | Number of mistakes (times) | Incubation period(s) |
| Normal control group | 1.44±2.02** | 226.73±104.37** |
| Model set | 13.57±3.73 | 10.75±3.63 |
| EXAMPLE 2 capsules | 5.73±1.52**# | 140.21±71.03**# |
| EXAMPLE Ex101 Capsule | 5.65±1.14**# | 134.47±53.27**# |
| EXAMPLE Ex111 Capsule | 5.02±1.86**# | 154.37±75.22**# |
| EXAMPLE 5 capsules | 3.24±1.47** | 196.24±82.26** |
| EXAMPLE 12 oral liquid | 5.54±1.31**# | 148.47±63.62**％ |
| Example Ex201 oral liquid | 5.42±1.27**# | 141.34±74.37**％ |
| Example Ex211 oral liquid | 5.11±1.53**# | 162.54±36.46**％ |
| Example 15 oral liquid | 3.15±1.66** | 203.76±65.16** |
| Nimodipine tablet group | 3.13±1.64** | 202.37±93.16** |
P <0.05 compared to model group; compared to the capsules of example 5, # P < 0.05; in comparison to the oral liquid of example 15,% P < 0.05.
3. Influence of rhizoma Gastrodiae capsule/oral liquid on rat brain tissue MDA, lipofuscin content and AChE activity
After the behavioral experiment of rat memory acquisition disorder caused by scopolamine is completed, the injection of scopolamine is continued for 5 days and the intragastric administration is continued for 5 days. The animals were sacrificed by decapitation, their whole brains (with cerebellum removed) were quickly taken from the ice box, weighed, homogenized with sterilized normal saline to make 10% brain homogenate, and the activities were measured according to the Malondialdehyde (MDA), acetylcholinesterase (AChE), and lipofuscin kit instructions, respectively. The results are shown in the following table, which shows that the composition of the present invention exhibits excellent effects of improving memory-related chemicals in vivo.
Table: influence of rhizoma Gastrodiae capsule/oral liquid on rat brain tissue MDA, lipofuscin content and AChE activity (x + -s, n ═ 10)
| Group of | MDA(nmoL/mgprot) | AChE(U/mgprot) | Lipofuscin (mu g/g brain tissue) |
| Normal control group | 12.89±2.02## | 1.07±0.18## | 1.13±0.36# |
| Model set | 19.24±1.84** | 1.62±0.24** | 1.74±0.44* |
| EXAMPLE 2 capsules | 17.34±1.38**#％ | 1.44±0.10**#％ | 1.48±0.16**#％ |
| EXAMPLE Ex101 Capsule | 17.13±1.13**#％ | 1.48±0.12**#％ | 1.52±0.23**#％ |
| EXAMPLE Ex111 Capsule | 16.47±1.32**#％ | 1.38±0.15**#％ | 1.40±0.22**#％ |
| EXAMPLE 5 capsules | 13.83±1.94## | 1.25±0.11*## | 1.26±0.30## |
| EXAMPLE 12 oral liquid | 17.18±1.44**#& | 1.41±0.13*#& | 1.42±0.18**#& |
| Example Ex201 oral liquid | 17.02±1.71**#& | 1.43±0.09**#& | 1.53±0.17**#& |
| Example Ex211 oral liquid | 16.31±1.57**#& | 1.40±0.14**#& | 1.38±0.20**#& |
| Example 15 oral liquid | 13.54±1.74## | 1.22±0.16*## | 1.23±0.23## |
| Nimodipine tablet group | 13.68±2.06## | 1.23±0.16*## | 1.19±0.27## |
P <0.05, P <0.01, compared to normal controls; compared with the model group, # P <0.05, # P < 0.01; in comparison to example 5 capsules,% P < 0.05; compared to the oral liquid of example 15, & P < 0.05.
The embodiments are only for illustrating the composition and efficacy of the invention, and not for limiting the scope of the invention, therefore, it will be apparent to those skilled in the art that similar modifications can be made without departing from the structure of the invention, and all such modifications are within the scope of the invention. These should also be construed as the scope of the present invention, and they should not be construed as affecting the effectiveness of the practice of the present invention or the applicability of the patent.
Claims (10)
1. The rhizoma gastrodiae brain-refreshing traditional Chinese medicine composition in the form of liquid is prepared from the following raw material medicines in parts by weight: 200-400 parts of gastrodia elata, 150-250 parts of earthworm, 200-400 parts of rhizoma acori graminei, 150-250 parts of polygala tenuifolia, 50-150 parts of prepared rehmannia root and 50-150 parts of cistanche deserticola.
2. The traditional Chinese medicine composition according to claim 1, which is prepared from the following raw material medicines in parts by weight: 300 parts of gastrodia elata, 200 parts of earthworm, 300 parts of rhizoma acori graminei, 200 parts of polygala tenuifolia, 100 parts of prepared rehmannia root and 100 parts of cistanche deserticola.
3. The Chinese medicinal composition according to claim 1, which further comprises a solvent such as water; for example, the liquid Chinese medicinal composition prepared from each 300 parts of rhizoma acori graminei comprises 2000-10000 parts by weight of water.
4. The Chinese medicinal composition according to claim 1, further comprising a bacteriostatic agent; for example, the concentration of the inhibitor in the liquid form of the Chinese medicinal composition is 0.1-0.3%, such as 0.15-0.25%, such as 0.2%.
5. The Chinese medicinal composition according to claim 1, which is in the form of a preparation of an oral liquid.
6. A Chinese medicinal composition according to any one of claims 1 to 5, which is prepared by a method comprising the steps of:
(1) extracting rhizoma Gastrodiae with 80% ethanol under reflux twice, each for 1 hr, mixing extractive solutions, and filtering to obtain filtrate T and residue;
(2) soaking Lumbricus with ethanol (such as 50-70% ethanol, such as 60% ethanol) for 60-80 hr (such as 72 hr), and filtering to obtain filtrate A;
(3) decocting rhizoma acori graminei, polygala tenuifolia, radix rehmanniae preparata, cistanche salsa and rhizoma gastrodiae dregs in the step (1) twice by adding water, decocting for 1-2 hours (for example, 1.5 hours) by adding water (for example, adding 7-9 times of water, for example, 8 times of water) for the first time, decocting for 0.5-1.5 hours (for example, 1 hour) by adding water (for example, adding 4-7 times of water, for example, 4 times of water) for the second time, filtering by times, combining filtrates, concentrating to obtain a clear paste with the relative density of 1.10-1.15 (90 ℃), cooling, adding ethanol to ensure that the alcohol content reaches 60%, standing for 24-72 hours (for example, 48 hours), and filtering to obtain a filtrate B for later use;
(4) mixing the filtrate T, the filtrate A and the filtrate B, recovering ethanol until no ethanol smell exists, adding 7.5-12.5 parts by weight of sodium benzoate, mixing uniformly, adding water to 5000 parts by weight, stirring uniformly, filtering, and adding water to 5000 parts by weight to obtain the rhizoma gastrodiae refreshing liquid traditional Chinese medicine composition; optionally subpackaging into oral liquid bottles to obtain 10ml oral liquid per bottle, or extracting rhizoma Acori Graminei, cortex et radix Polygalae, radix rehmanniae Preparata, Cistanchis herba, and rhizoma Gastrodiae residue in step (3) by the following steps (31) - (33): (31) decocting polygala tenuifolia, prepared rehmannia root and cistanche salsa twice, adding water into the gastrodia elata dregs in the step (1), decocting for 1-2 hours (for example, 1.5 hours) with water (for example, adding 7-9 times of water, for example, 8 times of water), decocting for 0.5-1.5 hours (for example, 1 hour) with water (for example, adding 4-7 times of water, for example, 4 times of water), filtering for several times, combining filtrates, concentrating to obtain a clear paste with the relative density of 1.10-1.15 (90 ℃), and cooling to obtain a clear paste 1 for later use; (32) decocting rhizoma acori graminei with water twice, decocting the rhizoma acori graminei with water containing glycine and sodium chloride for 1-2 hours (for example, 1.5 hours) for the first time (for example, adding 7-9 times of water, for example, 8 times of water), decocting the rhizoma acori graminei with water containing glycine and sodium chloride for 0.5-1.5 hours (for example, 1 hour) for the second time (for example, adding 4-7 times of water, for example, 4 times of water), filtering the mixture in multiple times, combining the filtrates, concentrating the combined filtrates to obtain clear paste with the relative density of 1.10-1.15 (90 ℃), and cooling the clear paste to obtain clear paste 2 for later use; (33) mixing the fluid extract 1 and the fluid extract 2, adding ethanol to make the alcohol content reach 60%, standing for 24-72 hours (for example, 48 hours), and filtering to obtain filtrate B for later use.
7. A method for preparing a Chinese medicinal composition comprising rhizoma Gastrodiae, Pheretima, rhizoma Acori Tatarinowii, radix Polygalae, radix rehmanniae Preparata, and herba cistanches, for example, the Chinese medicinal composition of any one of claims 1-6, comprising the steps of:
(1) extracting rhizoma Gastrodiae with 80% ethanol under reflux twice, each for 1 hr, mixing extractive solutions, and filtering to obtain filtrate T and residue;
(2) soaking Lumbricus with ethanol (such as 50-70% ethanol, such as 60% ethanol) for 60-80 hr (such as 72 hr), and filtering to obtain filtrate A;
(3) decocting rhizoma acori graminei, polygala tenuifolia, radix rehmanniae preparata, cistanche salsa and rhizoma gastrodiae dregs in the step (1) twice by adding water, decocting for 1-2 hours (for example, 1.5 hours) by adding water (for example, adding 7-9 times of water, for example, 8 times of water) for the first time, decocting for 0.5-1.5 hours (for example, 1 hour) by adding water (for example, adding 4-7 times of water, for example, 4 times of water) for the second time, filtering by times, combining filtrates, concentrating to obtain a clear paste with the relative density of 1.10-1.15 (90 ℃), cooling, adding ethanol to ensure that the alcohol content reaches 60%, standing for 24-72 hours (for example, 48 hours), and filtering to obtain a filtrate B for later use;
(4) mixing the filtrate T, the filtrate A and the filtrate B, recovering ethanol until no ethanol smell exists, adding 7.5-12.5 parts by weight of sodium benzoate, mixing uniformly, adding water to 5000 parts by weight, stirring uniformly, filtering, and adding water to 5000 parts by weight to obtain the rhizoma gastrodiae refreshing liquid traditional Chinese medicine composition; optionally subpackaging into oral liquid bottles to obtain 10ml oral liquid per bottle, or extracting rhizoma Acori Graminei, cortex et radix Polygalae, radix rehmanniae Preparata, Cistanchis herba, and rhizoma Gastrodiae residue in step (3) by the following steps (31) - (33): (31) decocting polygala tenuifolia, prepared rehmannia root and cistanche salsa twice, adding water into the gastrodia elata dregs in the step (1), decocting for 1-2 hours (for example, 1.5 hours) with water (for example, adding 7-9 times of water, for example, 8 times of water), decocting for 0.5-1.5 hours (for example, 1 hour) with water (for example, adding 4-7 times of water, for example, 4 times of water), filtering for several times, combining filtrates, concentrating to obtain a clear paste with the relative density of 1.10-1.15 (90 ℃), and cooling to obtain a clear paste 1 for later use; (32) decocting rhizoma acori graminei with water twice, decocting the rhizoma acori graminei with water containing glycine and sodium chloride for 1-2 hours (for example, 1.5 hours) for the first time (for example, adding 7-9 times of water, for example, 8 times of water), decocting the rhizoma acori graminei with water containing glycine and sodium chloride for 0.5-1.5 hours (for example, 1 hour) for the second time (for example, adding 4-7 times of water, for example, 4 times of water), filtering the mixture in multiple times, combining the filtrates, concentrating the combined filtrates to obtain clear paste with the relative density of 1.10-1.15 (90 ℃), and cooling the clear paste to obtain clear paste 2 for later use; (33) mixing the fluid extract 1 and the fluid extract 2, adding ethanol to make the alcohol content reach 60%, standing for 24-72 hours (for example, 48 hours), and filtering to obtain filtrate B for later use.
8. The use of the Chinese medicinal composition according to any one of claims 1 to 6 for the preparation of a medicament for the treatment or prevention of memory impairment and unresponsiveness.
9. Use of a Chinese medicinal composition according to any one of claims 1 to 6 in the preparation of a medicament for the treatment or prevention of brain atrophy.
10. The use of the Chinese medicinal composition according to any one of claims 1 to 6 for the preparation of a medicament for the treatment or prevention of brain dementia caused by stroke or brain trauma.
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Citations (3)
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|---|---|---|---|---|
| CN1583031A (en) * | 2004-06-01 | 2005-02-23 | 云南省昭通制药有限公司 | Composite gastrodia luber medicine and its preparation and use |
| CN1981852A (en) * | 2005-11-09 | 2007-06-20 | 北京奇源益德药物研究所 | Tall gastrodia tuber preparation with resuscitation-inducing function, its making and quality controlling method |
| CN104306745A (en) * | 2014-10-31 | 2015-01-28 | 云南永孜堂制药有限公司 | Quality control method for rhizoma gastrodiae capsule |
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2021
- 2021-09-10 CN CN202111059820.4A patent/CN113713047A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1583031A (en) * | 2004-06-01 | 2005-02-23 | 云南省昭通制药有限公司 | Composite gastrodia luber medicine and its preparation and use |
| CN1981852A (en) * | 2005-11-09 | 2007-06-20 | 北京奇源益德药物研究所 | Tall gastrodia tuber preparation with resuscitation-inducing function, its making and quality controlling method |
| CN104306745A (en) * | 2014-10-31 | 2015-01-28 | 云南永孜堂制药有限公司 | Quality control method for rhizoma gastrodiae capsule |
Non-Patent Citations (1)
| Title |
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| 詹合琴等: "天麻醒脑胶囊对沙土鼠脑缺血再灌注损伤的影响", 《中成药》 * |
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