CN116832066A - Application of cuttlefish ink extract in preparing medicine for treating hyperkinetic syndrome and depression - Google Patents
Application of cuttlefish ink extract in preparing medicine for treating hyperkinetic syndrome and depression Download PDFInfo
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- CN116832066A CN116832066A CN202310989071.8A CN202310989071A CN116832066A CN 116832066 A CN116832066 A CN 116832066A CN 202310989071 A CN202310989071 A CN 202310989071A CN 116832066 A CN116832066 A CN 116832066A
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- depression
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- 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
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY 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
- A61K2236/30—Extraction of the material
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY 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
- A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The application discloses application of a cuttlefish ink extract in preparing medicines for resisting hyperactivity and depression, wherein the cuttlefish extract and a compound composition thereof adopted by the application are natural components, have no side effect, have good activity for resisting hyperactivity and have good activity for treating depression.
Description
Technical Field
The application belongs to the technical field of biological medicines, and particularly relates to application of a sepia ink extract in preparation of anti-hyperkinetic syndrome and anti-depression medicines.
Background
Monoamine neurotransmitters are involved in the occurrence of a variety of mental diseases, such as attention deficit hyperactivity disorder (Attention Deficit Hyperactivity Disorder, ADHD), and clinical symptoms manifest as attention deficit and or hyperactivity. ADHD has complex etiology and individual variability, and the biological mechanisms of ADHD pathogenesis have not been elucidated to date. ADHD is currently considered to be a syndrome of multiple disorders caused by multiple causes, and is associated with multiple factors, such as genetics, psychosocial, neurobiology, and the like. Genetic factors are one of the main causes of ADHD onset, with heritability as high as 80%, and obvious family aggregation. Neurobiological and neuroimaging studies have found that ADHD infants suffer from frontal lobe function and cortical junction defects, with delayed cortical development leading to dysfunctions of execution, and thus problems with response inhibition, attention control and working memory. Dopamine, norepinephrine, 5-hydroxytryptamine disorders cause the core symptoms of ADHD.
Thus, current clinical treatments for ADHD are primarily western medicines that increase the inhibition of prefrontal lobe activity by modulating neurotransmitter levels, including the central stimulants methylphenidate, amphetamine, pimolin, the central norepinephrine-modulating drug tomoxetine, clonidine. NICE evidence-based suggests that methylphenidate and tomoxetine may be used as first-line treatments for ADHD. Tomoxetine with higher safety is recommended as a first-line therapeutic drug in the guidelines for prevention and treatment of Chinese attention deficit hyperactivity disorder. However, related chemicals may cause related adverse reactions while improving ADHD symptoms, including: can cause severe liver injury, and cause gastrointestinal reactions such as dizziness, headache, insomnia, somnolence, nausea, anorexia, dyspepsia, abdominal pain, etc. Therefore, a novel anti-hyperkinetic symptom drug which is safe, efficient and free of toxic and side effects is clinically needed.
In addition, depression (Depression) belongs to affective Mood Disorder (Mood dispenser), takes remarkable and durable low-lying Mood as basic clinical manifestation, has become a serious disease seriously affecting physical and mental health and life of patients, the incidence rate increases year by year, about 3.5 hundred million people in the world suffer from Depression, the incidence rate of swedish is 6.16%, the U.S. is 4.45%, and China is 3.02%, but the understanding of the etiology and pathogenesis is still unclear, so the disease is regarded as serious difficult disease.
Depression is a disease of complex etiology involving multiple systems, seriously jeopardizing the physical and mental health of humans, and world health organization predicts that depression will be one of the important diseases next to cardiovascular disease. Currently, there are three main modes of treatment for depression: drug therapy, psychotherapy and physical therapy, but chemical drug therapy is still the main treatment. The anti-depression chemical medicines on the market have the problems of poor curative effect, long medicine taking time, slow effect, relapse after stopping medicine taking, obvious adverse reaction and the like, and also threaten the health of patients while playing the treatment role. The incidence rate of patients suffering from light and moderate depression is increased year by year, but compared with the serious diseases such as tumors, diabetes, cardiovascular and cerebrovascular diseases and the like, the research and development of medicaments for treating depression are relatively lagged, and the contradiction between market supply and demand is serious, so that the research and development of modern antidepressant medicaments from traditional Chinese medicines and natural products is particularly urgent. Currently, antidepressants mainly include monoamine oxidase inhibitors, 5-HT reuptake inhibitors, NE reuptake inhibitors, and the like.
The cuttlefish ink melanin is a water insoluble biological macromolecule polymer, and consists of small oligomer molecules, and the chemical components are melanin and proteoglycan complex, mainly melanin protein combined by eumelanin and protein, polymer of tyrosine, water, fat and the like. Eumelanin is a precursor of two indole-structured molecules, DHI (5, 6-dihydroxyindole) and DHICA (5, 6-dihydroxyindole acid) oxidized from tyrosine, and sepia melanin is considered to be typical of natural eumelanin. The melanin (SIM) in the ink has hemostatic and adsorbing effects. However, no report on the improvement of monoamine neurotransmitters and depression by using the cuttlefish ink extract and the composition thereof for treating hyperactivity is found.
Aiming at the problems that the traditional anti-hyperkinetic symptoms and anti-depression western medicines are accompanied with various adverse reactions, the adaptive population is narrow, and the like, the application discovers that the cuttlefish ink extract and the compound composition thereof have good anti-hyperkinetic symptoms and anti-depression activity for the first time, and discovers that the cuttlefish ink extract has the activity of treating hyperkinetic symptoms and the anti-depression activity for the first time, expands the application range of the cuttlefish ink extract and provides more selection schemes for treating hyperkinetic symptoms and depression.
Disclosure of Invention
Aiming at the defects that the existing related diseases and western medicines have various adverse reactions, the adaptive crowd is narrow, and the like, the application provides the application of the cuttlefish ink extract with the anti-hyperkinetic and anti-depression activities and the compound composition thereof in the preparation of the mental disease medicines. The application discovers that the cuttlefish ink extract has the activity of treating hyperactivity and antidepressant, expands the application range of the cuttlefish ink extract, and provides more options for treating hyperactivity and depression.
The first aspect of the application provides an application of a sepia extract in preparing anti-hyperkinetic and anti-depression drugs, which takes the sepia extract as an active ingredient and prepares the anti-hyperkinetic and anti-depression drugs after being mixed with pharmaceutically or food acceptable traditional Chinese medicine decoction pieces, auxiliary materials or auxiliary additive components.
The medicine provided by the application can be solution, mixture, tablet, tincture, powder, capsule, pill, paper-type and the like, and the auxiliary materials and additives of the medicine are all conventional compositions.
The cuttlefish ink extract can be obtained by any existing method, and also can be obtained by the method, and the key of the application is not the extraction method of the cuttlefish ink extract nor the cuttlefish ink extract per se, and the key of the application is to discover that the cuttlefish ink extract has anti-hyperkinetic activity and anti-depression activity.
Further, the preparation method of the sepia ink extract provided by the application comprises the following steps:
s1: taking cuttlefish ink bag, cutting bag skin, and taking cuttlefish ink therein;
s2: stirring the cuttlefish ink obtained in the step S1, and synchronously performing ultrasonic extraction, wherein the ultrasonic extraction power is 25-50kHz, the stirring speed is 50-300rpm, and the time is 5-30min;
s3: centrifuging the ultrasonic dispersed cuttlefish ink in the step S2 for 10-20min, repeating the centrifugation for 2-6 times, and collecting the centrifugal precipitate;
s4: adding 5-10 times of precipitation weight water into the precipitate obtained in the step S3, and filtering by adopting a ceramic membrane;
s5: concentrating the suspension filtered in the step S4, and drying to obtain the cuttlefish ink extract.
Further, the squid ink is derived from any one or a combination of at least two of squid, sepia man, sepia tiger or sepia.
Further, the tubular centrifugal speed in the step S3 is 3000-10000rpm, and the filter pore diameter of the ceramic membrane in the step S4 is about 50 nm; in the step S5, the concentration is vacuum rotary evaporation, and the temperature is 30-60 ℃; the drying time is 1-2 days, and the temperature is 30-60 ℃.
The second aspect of the application provides a compound cuttlefish ink composition with anti-hyperkinetic and anti-depression activities, which comprises cuttlefish ink extract and a compound extract, wherein the compound extract is an extract of oyster, liquorice, jujube and ginger.
Further, the compound extract is obtained by soaking oyster, liquorice, jujube and ginger in water, refluxing and concentrating.
Further, the raw materials selected in the preparation process of the composite extract comprise 5-9 parts of oyster, 1-2 parts of liquorice, 5-9 parts of Chinese date and 1-2 parts of ginger.
The third aspect of the application provides a method for preparing the compound cuttlefish ink composition, and the obtained compound cuttlefish ink composition has both anti-hyperkinetic activity and anti-depression activity.
The preparation method comprises the following steps: taking 5-9 parts of oyster, 1-2 parts of liquorice, 5-9 parts of jujube and 1-2 parts of ginger according to parts by weight, then adding 10 times of water into the mixture to soak for 20min, carrying out reflux extraction for 1h, carrying out total extraction for 2 times, combining the extracting solutions, concentrating the extracting solutions to 1/10 of the volume of the extracting solution, adding 1 part of cuttlefish ink extract, stirring the mixture at a constant temperature of 40 ℃ for 1h, and preserving the mixture to obtain the cuttlefish ink compound composition.
The fourth aspect of the application provides an application of a compound cuttlefish ink composition in preparing anti-hyperkinetic and anti-depression drugs, wherein the compound composition has anti-hyperkinetic and anti-depression activities.
Furthermore, the cuttlefish ink compound composition is taken as an active ingredient, and is mixed with pharmaceutically or food acceptable traditional Chinese medicine decoction pieces, auxiliary materials or auxiliary additive ingredients to prepare the anti-hyperkinetic symptom and anti-depression drugs.
The medicine provided by the application can be solution, mixture, tablet, tincture, powder, capsule, pill, paper type and the like.
Advantageous technical effects
The application provides application of a cuttlefish ink extract in preparing medicines for resisting hyperkinetic symptoms and depression, and the cuttlefish extract and a compound composition thereof adopted by the application are natural components, have no side effects, have good activity for resisting hyperkinetic symptoms, and have good activity for treating depression. The application discovers that the cuttlefish ink extract has the activity of treating hyperactivity and antidepressant, expands the application range of the cuttlefish ink extract, and provides more options for treating hyperactivity and depression.
The cuttlefish ink extract provided by the application has no negative effect on the growth speed of animals, is high in safety and free of toxic and side effects, is a novel anti-hyperkinetic medicine and an anti-depression medicine which are safe, efficient and free of toxic and side effects, and has good effects on resisting depression on the basis of mainly having anti-hyperkinetic activity. Experimental data shows that the compound composition of the cuttlefish ink has good effects for treating infantile anti-hyperkinetic syndrome and anti-depression.
The compound cuttlefish ink composition provided by the application has very remarkable effects on treating infantile hyperkinetic syndrome and antidepressant, and has the advantages of high effective rate, low recurrence rate, no toxic or side effect, simple formula and low preparation cost. The adopted raw materials are natural substances, and other chemical substances are not added in the preparation method, so that the preparation method is environment-friendly.
Detailed Description
Those skilled in the art can, with the benefit of this disclosure, suitably modify the process parameters to achieve this. It is expressly noted that all such similar substitutions and modifications will be apparent to those skilled in the art, and are deemed to be included in the present application. While the application has been described with reference to preferred embodiments, it will be apparent to those skilled in the relevant art that variations and modifications can be made in the application described herein without departing from the spirit or scope of the application. The application is further illustrated by the following specific examples, which should not be construed as limiting the application.
The terms "comprising," "including," "having," "containing," or any other variation thereof, as used herein, are intended to cover a non-exclusive inclusion. For example, a composition, step, method, article, or apparatus that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, step, method, article, or apparatus.
The phrase "consisting of …" excludes any unspecified element, step or component. If used in a claim, such phrase will cause the claim to be closed, such that it does not include materials other than those described, except for conventional impurities associated therewith. When the phrase "consisting of …" appears in a clause of the claim body, rather than immediately following the subject, it is limited to only the elements described in that clause; other elements are not excluded from the stated claims as a whole.
When an equivalent, concentration, or other value or parameter is expressed as a range, preferred range, or a range bounded by a list of upper preferable values and lower preferable values, this is to be understood as specifically disclosing all ranges formed from any pair of any upper range limit or preferred value and any lower range limit or preferred value, regardless of whether ranges are separately disclosed. For example, when ranges of "1 to 5" are disclosed, the described ranges should be construed to include ranges of "1 to 4", "1 to 3", "1 to 2 and 4 to 5", "1 to 3 and 5", and the like. When a numerical range is described herein, unless otherwise indicated, the range is intended to include its endpoints and all integers and fractions within the range.
In some examples, the approximating language may correspond to the precision of an instrument for measuring the value. In the description and claims of the application, the range limitations may be combined and/or interchanged, if not otherwise specified, including all the sub-ranges subsumed therein.
The indefinite articles "a" and "an" preceding an element or component of the application are not limited to the requirement (i.e. the number of occurrences) of the element or component. Thus, the use of "a" or "an" should be interpreted as including one or at least one, and the singular reference of an element or component includes the plural reference unless the amount clearly dictates otherwise.
The description of the terms "one embodiment," "some embodiments," "examples," "specific examples," or "some examples," etc., herein describe means that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the application. In this specification, schematic representations of the above terms are not necessarily for the same embodiment or example. The technical features of the respective embodiments of the present application may be combined with each other as long as they do not collide with each other.
The materials and equipment used in the present application are commercially available or are those commonly used in the art, and the methods described in the examples are those commonly used in the art unless otherwise specified.
The application discloses a squid ink extract with good effect in the aspects of treating hyperactivity and depression for the first time by utilizing a recognized young SHR rat of an hyperactivity model animal for in-vivo animal experiments, and provides application of the squid ink extract in preparing medicines for resisting hyperactivity and depression.
The main functions of each component in the compound composition are as follows:
oyster is rich in microelements such as Zn, mg and Fe, the microelements have an important effect on improving the activity of tyrosine hydroxylase (dopamine synthesized speed-limiting enzyme), the main component of the cuttlefish ink is melanin, the cuttlefish ink has a unique nano structure, the microelements such as Fe and Zn are rich in various functional groups to form an organic state by chelation, the organic state is easier to be absorbed by an organism, the effect is obvious, the biological activity of the tyrosine hydroxylase is further promoted, the neurotransmitter level of organism dopamine and the like is regulated, and the ADHD symptom is further improved.
The ginger can regulate gastrointestinal tracts, volatile oil and gingerol in the ginger can play roles in protecting and promoting gastrointestinal peristalsis, enhancing digestion function, improving adverse reactions of the digestive system of patients with ADHD, and simultaneously has positive promotion effect on dopamine regulation; in the preparation process, the ginger can greatly reduce the fishy smell of oyster and cuttlefish ink and improve the mouthfeel.
The jujube is rich in multiple vitamins and microelements, is beneficial to the growth and development of children, wherein the jujube is rich in cyclic adenosine monophosphate, can improve the activity of the hydroxylase of the tyrosine, further promote the synthesis and metabolism of dopamine, has good taste correction effect, is beneficial to the improvement of the mouthfeel of the product, and is more suitable for children to take.
Further, the compound extract is obtained by soaking oyster, liquorice, jujube and ginger in water, refluxing and concentrating.
Further, the raw materials selected in the preparation process of the composite extract are 5-9 parts by weight of oyster, 1-2 parts by weight of liquorice, 5-9 parts by weight of Chinese date and 1-2 parts by weight of ginger.
Further, the application provides a method for preparing the cuttlefish ink compound composition.
The preparation method comprises the following steps: taking 5-9 parts of oyster, 1-2 parts of liquorice, 5-9 parts of jujube and 1-2 parts of ginger according to parts by weight, then adding 10 times of water into the mixture to soak for 20min, carrying out reflux extraction for 1h, carrying out total extraction for 2 times, combining the extracting solutions, concentrating the extracting solutions to 1/10 of the volume of the extracting solution, adding 1 part of cuttlefish ink extract, stirring the mixture at a constant temperature of 40 ℃ for 1h, and preserving the mixture to obtain the cuttlefish ink compound composition. The preparation method has no organic additive in the whole process, and the preparation process is environment-friendly.
The medicine provided by the application can be solution, mixture, tablet, tincture, powder, capsule, pill, powder, paper type and the like.
The application is further illustrated below in conjunction with specific examples, which are not intended to be limiting of the application.
Example 1 preparation of ink Sepiae extract
S1: taking commercially available sepia tiger ink sacs, cutting open the capsule skin, and taking sepia tiger ink therein;
s2: ultrasonic extracting the sepia ink in the step S1 by stirring at the ultrasonic extracting power of 25kHz and the stirring speed of 50rpm for the following time: 30min;
s3: centrifuging the dispersed cuttlefish ink in S2 for 20min by tubular centrifugation at 3000r/min, repeatedly centrifuging for 2 times, and collecting centrifugal precipitate;
s4: adding 5 times of water into the sediment collected in the step S3, adopting ceramic membrane filtering equipment, selecting membrane materials with the pore diameter of 50nm, regulating the flow rate of the reaction according to the characteristics of the materials, controlling the overall reaction pressure to be 0.2MPa, and controlling the average flux of the membrane to be 1m 2 /h；
S5: carrying out vacuum rotary evaporation on the suspension after filtering of the S4, wherein the temperature is 30 ℃; drying for 1 day at 60deg.C to obtain cuttlefish ink extract.
Example 2 preparation of ink Sepiae extract
S1: taking cuttlefish-free cuttlefish and cuttlefish ink sacs, cutting open the capsule skin, and taking cuttlefish ink therein;
s2: ultrasonic extracting the sepia ink in the step S1 by stirring at the ultrasonic extracting power of 50kHz and the stirring speed of 300rpm for the following time: 5min;
s3: centrifuging the dispersed cuttlefish ink in S2 for 10min by tubular centrifugation 10000r/min, repeatedly centrifuging for 2 times, and collecting centrifugal precipitate;
s4: adding 10 times of water into the sediment collected in the step S3, adopting ceramic membrane filtering equipment, selecting membrane materials with pore diameter of 40nm, regulating the flow rate of the reaction according to the characteristics of the materials, controlling the overall reaction pressure to be 0.3MPa, and controlling the average flux of the membrane to be 1m 2 /h；
S5: concentrating the suspension after filtering the S4 into vacuum rotary evaporation, wherein the temperature is 60 ℃; the drying time is 2 days, and the temperature is 30 ℃ to obtain the cuttlefish ink extract.
Example 3 preparation of Compound composition of ink Sepiae
Taking 5 parts of oyster, 1 part of liquorice, 5 parts of jujube and 1 part of ginger according to the weight proportion, adding 10 times of water each time for 20min, reflux-extracting for 1h, extracting for 2 times, combining the extracting solutions, concentrating to 1/10 of the volume of the extracting solution, adding 1 part of the cuttlefish ink extract of example 1, stirring at a constant temperature of 40 ℃ for 1h, and preserving for later use.
Example 4 preparation of Compound composition of ink Sepiae
Taking 9 parts of oyster, 2 parts of liquorice, 9 parts of jujube and 2 parts of ginger according to the weight proportion, adding 10 times of water into each time for 20min, carrying out reflux extraction for 1h, extracting for 2 times, mixing the extracting solutions, concentrating to 1/10 of the volume of the extracting solution, adding 2 parts of the cuttlefish ink extract of the example 2, stirring at a constant temperature of 40 ℃ for 1h, and preserving for later use.
Example 5 preparation of ink Sepiellae seu sepiae composition preparation
Taking 7 parts of oyster, 2 parts of liquorice, 7 parts of jujube and 2 parts of ginger according to the weight proportion, adding 10 times of water each time for 20min, reflux-extracting for 1h, extracting for 2 times, mixing the extracting solutions, concentrating to 1/10 of the volume of the extracting solution, adding 2 parts of the cuttlefish ink extract of the example 2, stirring at a constant temperature of 40 ℃ for 1h, and preserving for later use.
Adding appropriate amount of agar, decocting in water, adding quantitative red bean paste, stirring to melt, adding the above extractive solution, decocting, and pouring into a mold to obtain soup/gum-based candy.
Comparative example 1
Taking 9 parts of oyster, 2 parts of liquorice, 9 parts of jujube and 2 parts of ginger according to the weight proportion, adding 10 times of water into each time for 20min, carrying out reflux extraction for 1h, extracting 2 times, mixing the extracting solutions, concentrating to 1/10 of the volume of the extracting solution, and preserving for later use.
Comparative example 2
Taking commercially available cuttlefish ink sacs, cutting open the capsule skin, taking cuttlefish ink therein, and drying for 2 days at 30deg.C.
Further, the performance of the cuttlefish ink extract and the compound composition thereof for regulating monoamine neurotransmitter pharmacodynamics is tested and demonstrated, and the performance is specifically as follows:
the samples of examples 1 to 5 and comparative examples 1 to 2 were accurately weighed and a solution was prepared at a gastric lavage dose of 500mg/kg (in terms of sepia extract). The spontaneous SHR rats of the hyperkinetic symptom rat model of 3-4 weeks old are selected as the model, and the WKY rats of the same age are used as the control animals. According to the effective dose of the rat and the conversion coefficient of the body surface of the rat and the human body. The cuttlefish ink extract is dissolved in sodium carboxymethyl cellulose, and the administration dosage is 500mg/kg (calculated by cuttlefish ink extract), and 1mL of medicinal liquid is added to each 100g of the weight of the rat for gastric lavage, 1 time a day, and 15 days continuously. 8 WKY rats are normal control group, namely blank group, and gastric lavage physiological saline; the 64 SHR rats were evenly divided into 8 groups according to body weight, a model group (physiological saline) and each experimental group (examples and comparative examples).
(1) Weight of body
Animals were monitored daily for changes in body weight.
The WKY rats and the SHR rats have objective differences in body type and weight due to different varieties, so that the comparison of body weight only compares the SHR rats. Initial body weight of the group, body weight differences of SHR rats of each group were not statistically significant (P > 0.05); the weight differences between groups of SHR rats at 7 and 15 days of gastric lavage were also statistically significant (P > 0.05). The results are shown in Table 1, and the results show that each tested medicament has high safety and no toxic or side effect.
TABLE 1 rat weight status
| Group of | Initial body weight/g | Weight/g 7 days | 15 days weight/g |
| Blank group | 180.0±3.2 | 229.43±2.3 | 281.5±2.7 |
| Model group | 114.2±4.5 | 146.80±5.2 | 198.05±5.1 |
| Example 1 | 116.1±4.7 | 155.92±5.9 | 203.2±6.2 |
| Example 2 | 115.2±4.5 | 152.4±6.0 | 204.7±5.8 |
| Example 3 | 116.3±4.8 | 156.3±4.8 | 206.7±5.2 |
| Example 4 | 114.8±4.5 | 158.3±6.2 | 205.8±5.4 |
| Example 5 | 113.9±4.0 | 157.2±5.5 | 205.7±5.0 |
| Comparative example 1 | 114.7±4.3 | 154.8±5.8 | 205.9±5.2 |
| Comparative example 2 | 115.2±3.9 | 156.7±4.4 | 204.2±4.8 |
(2) Enzyme-linked immunosorbent assay for determining neurotransmitters in rat brain tissues
An enzyme-linked immunosorbent assay kit for detecting neurotransmitter levels in rat brain tissues according to the specification. The classical monoamine hypothesis suggests that a decrease in DA, NE, 5-HT levels is associated with the onset of hyperactivity. SHR rats are ideal animal models of ADHD, and there is evidence for both behavioural and pathological evidence that they have a high degree of agreement with the ADHD model.
The experimental results are shown in Table 2, and experimental data show that the DA content and the 5-HT content in brain tissues of rats in the ADHD model group are obviously lower than those of rats in the blank group; however, the levels of Dopamine (DA) and 5-hydroxytryptamine (5-HT) in brain tissue of ADHD rats could be significantly up-regulated to varying degrees after each group of examples, but none of the NE data was significantly different; and comparative example 1 increased the DA and 5-HT levels in the rat brain, but there was no significant difference compared to the model group, and comparative example 2 increased the DA and 5-HT levels in the rat brain, and there was a significant difference compared to the model group. It is demonstrated that the squid ink extract and the compound composition thereof (examples 1 to 5) can significantly increase DA and 5-HT levels in brain tissue of hyperkinetic rat, thereby effectively treating ADHD.
TABLE 2 detection of monoamine neurotransmitters in rat brain tissue of each group
| Group of | DA/(pg/mL) | 5-HT/(ng/L) | NE/(ng/L) |
| Blank group | 73.57±8.48 | 416.31±22.83 | 206.61±19.82 |
| Model group | 48.03±3.66 ** | 212.57±20.72 ** | 171.71±10.58 |
| Example 1 | 62.34±8.04 # | 360.73±39.79 ## | 172.31±22.67 |
| Example 2 | 60.21±4.56 # | 370.52±17.30 ## | 185.41±39.01 |
| Example 3 | 66.46±6.63 # | 365.83±30.83 ## | 172.73±16.81 |
| Example 4 | 68.74±8.37 # | 378.22±50.38 ## | 176.62±14.81 |
| Example 5 | 64.55±5.08 # | 362.22±29.17 ## | 191.22±35.10 |
| Comparative example 1 | 50.02±4.67 * | 232.58±15.48 ** | 173.71±27.96 |
| Comparative example 2 | 55.41±4.56 * | 286.73±34.59 **# | 166.83±22.02 |
Note that: in comparison with the blank set of the cells, * p＜0.05, ** p is less than 0.01; in comparison with the set of models, # p＜0.05, ## p＜0.01
example 6 clinical study of sepia extract and its Compound for improving childhood hyperkinetic syndrome
General data
In clinical cases, a total of 72 patients with infantile hyperactivity were selected, and randomly divided into 3 treatment groups and one control group, each group having 18 cases. Each group of sex, age, disease course and the like is statistically processed, and the difference has no significance (P is more than 0.05) and has comparability.
Therapeutic method
(1) The control group does not take medicine, and only carries out conventional psychological treatment and family treatment according to the doctor's advice.
(2) The treatment groups were ritaline positive and example 1 treatment group, example 3 treatment group.
Usage and dosage: the control group took ritalin tablets 5mg each time twice daily; the extracts of example 1 and example 3 were taken in the morning and evening, respectively, and a treatment course was 4 weeks.
Standard of efficacy
The effect is shown: the hyperactivity is obviously improved, the attention is focused, the emotion is stable, and the learning score reaches the level of the children of the same age
The method is effective: the symptom of hyperactivity is improved, attention is focused slightly than before, and the achievement is improved
Invalidation: none of the symptoms of hyperactivity are improved
Treatment results: each group of gender, age and disease course is counted, the related effects are counted and analyzed, the total effective rate and recurrence rate of clinical treatment are counted specifically, the specific data are shown in table 3,
TABLE 3 Total effective rate and recurrence rate results for clinical treatment (%)
In all cases, the treatment is carried out for 3 courses, the treatment results are shown in Table 3, the total effective rate of the 3 treatment groups is 72.2%, 66.7% and 66.7% respectively compared with the total effective rate of the control group, the difference is statistically significant (P is less than 0.05), which shows that the curative effect of the application in the example 1 and the example 3 on the infantile hyperkinetic symptoms is obviously better than that of the control group; compared with 27.8% of the recurrence rate of the control group, the recurrence rates of the three treatment groups are respectively 16.7%, 11.11% and 6.67%, the recurrence rates of the three treatment groups are obviously reduced, the difference is statistically significant (P is less than 0.05), the recurrence rate of the application in the example 1 and the example 3 is lower than that of the positive medicine group, but the recurrence rate of the pediatric hyperactivity disease can be obviously reduced, and no obvious adverse reaction is seen in all patients in the treatment groups, so that the sepia treatment of the pediatric hyperactivity disease is safe and effective, and has no side effect.
In addition, oyster in the cuttlefish ink compound of the embodiment 3 is rich in microelements such as Zn, mg and Fe, and the supplementation of related microelements plays an important role in improving the activity of tyrosine hydroxylase (the speed-limiting enzyme for dopamine synthesis). Experiments show that the main component of the cuttlefish ink is melanin, has a unique nano structure and is rich in various functional groups; fe. The Zn and other microelements are chelated with the Zn to form an organic state, so that the Zn and other microelements are easier to be absorbed by organisms, the effect is obvious, the biological activity of tyrosine hydroxylase is further promoted, the neurotransmitter level of organism dopamine and other neurotransmitters is regulated, and the ADHD symptoms are further improved. In addition, pb affects neurotransmitter production, affects childhood neural development, leading to the onset of hyperactivity. Experiments show that the cuttlefish ink has positive effects on eliminating and preventing Pb accumulation in the body, and further has good effects on improving and preventing ADHD. The ginger regulates the gastrointestinal tract, the volatile oil and gingerol in the ginger can play a role in protecting and promoting gastrointestinal peristalsis, enhancing digestion function, improving adverse reactions of the digestive system of patients with ADHD, and simultaneously has a positive promoting effect on dopamine regulation; in addition, in the preparation process, the ginger can greatly reduce the fishy smell of oyster and cuttlefish ink and improve the mouthfeel. The jujube is rich in multiple vitamins and microelements, is beneficial to the growth and development of children, wherein the jujube is rich in cyclic adenosine monophosphate, can improve the activity of the hydroxylase of the tyrosine, further promote the synthesis and metabolism of dopamine, has good taste correction effect, is beneficial to the improvement of the mouthfeel of the product, and is more suitable for children to take.
Furthermore, the anti-depression performance of the cuttlefish ink extract and the compound composition thereof is tested and demonstrated, and the specific steps are as follows:
a model of mouse depression was replicated using a chronically unpredictable model approach to Wen Heying Challenge (CUMS). Except for normal groups of mice, each group of mice receives a method of composite multi-factor modeling randomly every day, and the method specifically comprises the following 8 steps: fasted and water-inhibited for 24 hours; binding for 3 hours; swimming at 4 ℃ for 5 minutes; heat stress at 45 ℃ for 5 minutes; electrically stimulating for 1 minute; clamping the tail for 1 minute; wet padding for 24 hours; the cage was tilted at 45 ° for 24 hours. Modeling lasted for 6 weeks and stress factors were distributed according to a random number table method, making mice unpredictable for the occurrence of irritation.
After 3 days of adaptation, 90 ICR male mice were randomly divided into 9 groups of 10 animals each. After molding for 3 weeks, the control group and the model group were given distilled water for gastric lavage every day, and the samples of examples 1 to 5 and comparative examples 1 to 2 were given an appropriate amount (in terms of 500mg/kg, based on sepia extract) respectively.
The observation indexes are as follows:
(1) General state observation
Macroscopic characterization of each group of mice, including mental state, posture, voluntary activity, resistance during molding, hair color, gloss, and stool texture, etc., was mainly observed, and weights of each group of mice were weighed and recorded the last day of each week, one day before molding began, 1 st, 2 nd, 3 rd, 4 th, 5 th, 6 th week, etc., respectively. Last day of week 8 a.m.: 00 mice were given a fixed weight of food, the next morning 8:00 the remaining food weight was weighed and used to calculate the food intake of the mice. The calculation formula of the 24h food intake of the mice is as follows: food intake = weight of food administered (g) -weight of food remaining (g).
The weights of the mice in each group are shown in Table 4, and the feed intake of the mice in each group is shown in Table 5, and the data shows that the mice in each group are active, quick in response, sensitive in action, good in mental condition, smooth and glossy in hair, moderate in stool dryness and softness, and substantially the same in weight and feed intake before the molding starts. However, as the molding continues, the molding mice except the normal group gradually show reduced reactivity to stress, reduced liveness, listlessness, and shrinkage of the binding pile, disordered and rough hair, loss of luster, obvious difference in appearance from the normal group mice, and non-forming of feces; the intervention of each experimental group of mice was started daily after 3 weeks of molding until the molding was completed at week 6.
The body weights of mice in each group started at the end of the first week of modeling had significant statistical differences (P < 0.01) compared to the normal group; model mice fed significantly less food than normal group (P < 0.01) at the beginning of the second weekend of modeling; the drug intervention is started from week 4, the activity level of the mice in the groups 1-5 is gradually recovered after the intervention, the struggling resistance degree is obviously enhanced in the daily modeling process compared with the mice in the model group, the weight and the feeding capacity are obviously increased compared with those of the mice in the CUMS model group (P <0.05 and P < 0.01), the fecal texture recovery of the mice in the groups 3-5 is obvious, and the state of the animals in the groups 1-2 is improved to a certain extent, but no obvious difference is seen.
Table 4 weight change of mice in each group (n=10)
Note that: in comparison with the normal group, * P＜0.05， ** p is less than 0.01; in comparison with the set of models, # P＜0.05， ## P＜0.01。
table 5 mice of each group fed food (n=10)
| Group of | 0 week (g) | Week 1 (g) | Week 2 (g) | Week 3 (g) | Week 4 (g) | Week 5 (g) | Week 6 (g) |
| Blank group | 4.26±0.06 | 4.41±0.06 | 4.63±0.09 | 5.34±0.12 | 6.12±0.13 | 6.07±0.16 | 6.10±0.22 |
| Model group | 4.32±0.08 | 3.83±0.11 ** | 3.79±0.10 ** | 3.82±0.11 ** | 3.86±0.11 | 3.91±0.13 | 3.89±0.13 |
| Example 1 | 4.33±0.12 | 3.90±0.14 ** | 3.81±0.11 ** | 3.81±0.11 ** | 4.29±0.11 ## | 4.61±0.13 ## | 4.74±0.18 ## |
| Example 2 | 4.289±0.10 | 3.88±0.11 ** | 3.80±0.11 ** | 3.87±0.12 ** | 4.34±0.11 ## | 4.65±0.17 | 4.80±0.18 ## |
| Example 3 | 4.32±0.12 | 3.86±0.10 ** | 3.77±0.11 ** | 3.78±0.10 ** | 4.57±0.14 ## | 4.7±0.17 ## | 4.99±0.17 ## |
| Example 4 | 4.32±0.13 | 3.90±0.11 ** | 3.84±0.13 ** | 3.78±0.13 ** | 4.56±0.11 ## | 4.84±0.20 | 5.14±0.21 ## |
| Example 5 | 4.32±0.13 | 3.88±0.12 ** | 3.78±0.12 ** | 3.79±0.11 ** | 4.49±0.18 ## | 4.73±0.16 ## | 4.97±0.18 ## |
| Comparative example 1 | 4.34±0.12 | 3.87±0.15 ** | 3.84±0.20 ** | 3.78±0.19 ** | 3.97±0.22 | 4.02±0.20 | 4.03±0.21 |
| Comparative example 2 | 4.33±0.11 | 3.93±0.15 ** | 3.85±0.15 ** | 3.80±0.13 ** | 3.951±0.17 | 4.02±0.16 | 4.03±0.20 |
Note that: in comparison with the normal group, * P＜0.05， ** p is less than 0.01; in comparison with the set of models, # P＜0.05， ## P＜0.01。
(2) Syrup preference experiment
Sugar water preference experiments were performed on the last day of the week before the start of molding, 1, 2, 3, 4, 5,6 weeks of molding, respectively. The mice were trained for their suitability for drinking water containing sugar 72 hours before the beginning of the experiment, by first placing 2 bottles of 1% sucrose solution simultaneously per cage in the first 24 hours, followed by a bottle of 1% sucrose solution and a bottle of purified water in the next 24 hours. Finally, the mice are fasted and forbidden for 24 hours, and then officially begin to carry out the syrup preference experiment. And (3) testing the mice in a single cage, wherein each cage is simultaneously supplied with one bottle of 1% sucrose water and one bottle of purified water, taking the two water bottles out after freely drinking for 1 hour, weighing, and calculating the sugar water drinking amount and the purified water drinking amount of the mice.
Syrup preference ratio = syrup drinking amount (g)/syrup drinking amount + pure water drinking amount (g) x 100%.
Table 6 describes the body sugar water preference rate of each group of mice, and the experiment was mainly used for evaluating the pleasure loss degree of the experimental mice, and helping to judge the depression-like behaviors. The results show that the sugar water preference rate of each group of mice is basically consistent before the molding is started, and after one week of molding, the sugar water preference degree of the mice in the CUMS model group is obviously reduced compared with that of the mice in the normal group, and the lower sugar water preference rate is kept until the molding is finished (P < 0.01); three weeks after molding, mice of groups 1-5, comparative groups 1-2 were subjected to intervention. Starting on weekend 4, the sugar water preference rates of mice in the treatment groups of examples 1-5 all showed statistical differences (P < 0.01) compared to the CUMS model group, with little improvement but no significant differences seen in comparative examples 1-2.
Table 6 preference rate of sugar water for mice of each group (n=10)
| Group of | 0 week (%) | Week 1 (%) | Week 2 (%) | Week 3 (%) | Week 4 (%) | Week 5 (%) | Week 6 (%) |
| Blank group | 0.76±0.01 | 0.78±0.01 | 0.79±0.01 | 0.79±0.02 | 0.79±0.02 | 0.78±0.02 | 0.78±0.03 |
| Model group | 0.77±0.01 | 0.57±0.02 ** | 0.48±0.01 ** | 0.52±0.01 ** | 0.50±0.01 | 0.48±0.02 | 0.44±0.01 |
| Example 1 | 0.78±0.02 | 0.58±0.02 ** | 0.48±0.01 ** | 0.51±0.01 ** | 0.56±0.01 ## | 0.61±0.02 ## | 0.65±0.02 ## |
| Example 2 | 0.77±0.02 | 0.58±0.02 ** | 0.47±0.01 ** | 0.52±0.02 ** | 0.57±0.02 ## | 0.62±0.02 ## | 0.64±0.02 ## |
| Example 3 | 0.77±0.02 | 0.57±0.01 ** | 0.46±0.01 ** | 0.51±0.01 ** | 0.58±0.02 ## | 0.63±0.02 ## | 0.66±0.02 ## |
| Example 4 | 0.77±0.02 | 0.58±0.02 ** | 0.46±0.02 ** | 0.50±0.02 ** | 0.61±0.02 ## | 0.66±0.03 ## | 0.69±0.03 ## |
| Example 5 | 0.78±0.02 | 0.57±0.02 ** | 0.46±0.01 ** | 0.49±0.01 ** | 0.58±0.02 ## | 0.63±0.02 ## | 0.69±0.02 ## |
| Comparative example 1 | 0.78±0.02 | 0.56±0.02 ** | 0.46±0.02 **** | 0.50±0.03 ** | 0.53±0.03 | 0.49±0.02 | 0.47±0.02 # |
| Comparative example 2 | 0.77±0.02 | 0.58±0.02 ** | 0.46±0.02 | 0.50±0.02 ** | 0.53±0.02 | 0.49±0.02 | 0.48±0.02 # |
Note that: in comparison with the normal group, * P＜0.05, ** p is less than 0.01; in comparison with the set of models, # P＜0.05， ## P＜0.01。
(3) Open field experiment
The self-made open field box is 40cm in height, 50cm long at the bottom edge, and the bottom surface is equally divided into 25 small grids, wherein 9 small grids in the middle are called a central area. A digital camera is erected right above the box body, and the height is based on the condition that the whole box body is covered by the view field. And (3) carrying out open field experiments after the molding is finished at the 6 th week, wherein the indoor environment needs to be kept quiet and the light is soft in the experimental process. The mice were first acclimatized in the experimental environment for 10 minutes, then the laboratory operators gently put the mice in the center of the open field box, and the activity of the mice was recorded within 5 minutes. After each recording, the whole open field box is cleaned, urine and feces left by the mice are cleaned by wet towels, and then 75% alcohol is sprayed to remove residual odor. Ensuring that the open field box has no foreign odor, then putting the next mouse, and carrying out experiments in sequence. The observation indexes mainly comprise (1) the number of horizontal crossing lattices of the mice (counted by four limbs entering the lattices); (2) number of erections (two front paws vacated or climbing the wall); (3) number of modification times; (4) fecal grain number. The measurement was performed in a quiet environment using a single blind method, and the total distance of movement, the number of central zone entries, and the central zone residence time were observed for each group of mice.
Table 7 results of the mouse open field experiment (n=10)
| Group of | Total distance of sports (cm) | Number of central zone entries (times) | Residence time in the central zone(s) |
| Blank group | 3355.42±137.81 | 7.8±1.03 | 9.80±1.93 |
| Model group | 2761.36±152.29 ** | 4.2±0.92 ** | 7.40±2.22 * |
| Example 1 | 2903.33±105.11 # | 5.0±0.47 # | 8.00±1.63 |
| Example 2 | 2878.92±77.62 # | 5.0±0.67 # | 8.50±1.84 |
| Example 3 | 3088.93±79.30 ## | 5.3±0.67 # | 8.80±1.81 |
| Example 4 | 3064.39±89.66 ## | 6.0±0.82 ## | 9.90±1.20 # |
| Example 5 | 3177.29±98.28 ## | 5.2±0.79 # | 8.80±1.23 # |
| Comparative example 1 | 2829.4±109.56 | 4.7±0.67 | 8.00±1.63 |
| Comparative example 2 | 2902.20±118.79 | 4.8±0.63 | 8.10±1.91 |
Note that: in comparison with the normal group, * P＜0.05, ** p is less than 0.01; in comparison with the set of models, # P＜0.05， ## P＜0.01。
table 7 shows the results of the open field experiments of mice, and from the data results, the total movement distance and the central zone entry frequency of the mice in the CUMS model group are statistically different from those of the mice in the normal group (P <0.01 and P < 0.05), the total movement distance, the central zone entry frequency and the central zone residence time of the mice in the intervention group in examples 1-5 are significantly increased compared with the mice in the model group (P <0.01 and P < 0.05), and the mice in the comparison example 1-2 are improved, but no significant difference is seen.
(4) Forced swimming experiment
Forced swimming is a behavior destinationexperiment method, by placing animals in a limited environment, making them struggle in the environment, trying to escape, but not escaping, so as to form a non-avoidable compression environment, after a period of time, the animals will show a typical 'immobile state', and then observing and recording a series of parameters of the process of producing a destinationstate by the animals. The experiment can be used for evaluating the depression-like behavior of animals and the action effects of antidepressants and antidepressants.
The forced swimming experiment was performed in two steps. First, each mouse was placed individually in a transparent glass beaker having a diameter of 19cm and a height of 24cm one day before the experiment, and normal-temperature pure water (24.+ -. 1 ℃ C.) was poured into the beaker to a water depth of 10 cm. Each mouse swim for 15 minutes as a "forward swim" before the beginning of the formal experiment, which is an unexplained stress to the mice, can cause a "depressive reaction". And then taking the mice out of the swimming pool, drying and putting the mice into a cage. After the open field experiment is finished, formal experiments are carried out, and each experimental mouse forcedly swims for 6 minutes and the accumulated duration of the motionless state for 4 minutes is recorded. The standard for judging the static state is as follows: the mice stopped struggling, floating on the water surface, only the nostrils were exposed to breathe, and the limbs were occasionally swimming to keep the body from sinking.
Table 8 mice forced swimming immobility time (n=10)
Note that: in comparison with the normal group, * P＜0.05, ** p is less than 0.01; in comparison with the set of models, # P＜0.05， ## P＜0.01。
table 8 records the immobility time of the mice in forced swimming, and from the results of forced swimming experiments, the immobility time of the mice in the CUMS model group is significantly higher than that of the mice in the normal group (P < 0.01), compared with the immobility time of the mice in the examples 1-5 groups which is reduced compared with that of the mice in the model group, and the mice in the comparative examples 1-2 groups are not significantly improved.
Example 7 clinical study of sepia extract and its Compound for improving depression
General data
In clinical cases, 48 patients with mild-moderate depression are selected, and the patients are randomly divided into 1 treatment group and one control group, and the treatment course is 12 weeks. Each group of sex, age, disease course and the like is statistically processed, and the difference has no significance (P is more than 0.05) and has comparability.
Therapeutic method
(1) Control group escitalopram oxalate.
(2) The treatment group was given the compound composition of example 4.
Usage and dosage: the control group was taken with escitalopram oxalate (Laishipu, produced by Ling Bei medicine Co., ltd., national drug standard H20150163, specification: 10 mg/tablet) 10 mg/day, and was taken in the morning. The experimental group took example 4, orally in the morning and evening, respectively, and a treatment course is 4 weeks.
Standard of efficacy
And (3) healing: the symptoms of patients almost disappear, and the curative effect index is more than or equal to 75 percent
The effect is shown: the symptoms of patients basically disappear, the symptoms sometimes disappear soon, and the curative effect index is more than or equal to 50% and less than 75%
The method is effective: the symptoms of patients hardly disappear, but the symptoms are relieved before, and the curative effect index is less than 50% and is more than 30%)
Invalidation: the symptoms of the patients are not disappeared and are not lightened, and the curative effect index is less than 30 percent
Treatment results: each group of gender, age and disease course is counted, the related effects are statistically analyzed, the total effective rate and recurrence rate of clinical treatment are specifically counted, and specific data are shown in table 9. After 12 weeks of treatment, the total effective rate of the treatment group was comparable to that of the control group (75.0% vs 79.2%), but the number of significant cases was significantly higher than that of the control group (58.3% vs 41.7%), and no significant adverse reaction was observed.
TABLE 9 Total effective rate and recurrence rate results for clinical treatment (%)
Wherein, total effectiveness = cure + onset + effectiveness.
In conclusion, the cuttlefish ink extract and the compound composition thereof provided by the application have no negative influence on the growth speed of animals, are high in safety and have no toxic or side effect, are novel anti-hyperkinetic drugs and antidepressant drugs which are safe, efficient and have no toxic or side effect, have good effects on the basis of mainly having anti-hyperkinetic activity, and have good effects on the treatment of the infantile anti-hyperkinetic symptoms and the antidepressant on the basis of experimental data.
The above description of the embodiments is only for aiding in the understanding of the method of the present application and its core ideas. It should be noted that it will be apparent to those skilled in the art that various modifications and adaptations of the application can be made without departing from the principles of the application and these modifications and adaptations are intended to be within the scope of the application as defined in the following claims.
Claims (10)
1. The application of the cuttlefish ink extract in preparing the anti-hyperkinetic and anti-depression drugs is characterized in that the cuttlefish ink extract is taken as an active ingredient to be mixed with pharmaceutically or food acceptable traditional Chinese medicine decoction pieces, auxiliary materials or auxiliary additives to prepare the anti-hyperkinetic and anti-depression drugs.
2. The use according to claim 1, wherein the method for preparing the ink-jet extract comprises the steps of: s1: taking cuttlefish ink bag, cutting bag skin, and taking cuttlefish ink therein;
s2: stirring the cuttlefish ink obtained in the step S1, and synchronously performing ultrasonic extraction, wherein the ultrasonic extraction power is 25-50kHz, the stirring speed is 50-300rpm, and the time is 5-30min;
s3: centrifuging the ultrasonic dispersed cuttlefish ink in the step S2 for 10-20min, repeating the centrifugation for 2-6 times, and collecting the centrifugal precipitate;
s4: adding 5-10 times of precipitation weight of water into the precipitate obtained in the step S3, and filtering by adopting a ceramic membrane;
s5: concentrating the suspension filtered in the step S4, and drying to obtain the cuttlefish ink extract.
3. The use according to claim 2, wherein said squid ink is derived from any one or more of squid, sepia man, tiger spot squid or squid species.
4. Use according to any one of claims 2-3, wherein the tubular centrifugation speed in step S3 is 3000-10000rpm and the ceramic membrane filtration pore size in step S4 is about 50 nm; in the step S5, the concentration is vacuum rotary evaporation, and the temperature is 30-60 ℃; the drying time is 1-2 days, and the temperature is 30-60 ℃.
5. An ink-sepia compound composition having anti-hyperactivity and anti-depression activity, which comprises the ink-sepia extract of any one of claims 1 to 4 and a compound extract of oyster, licorice, jujube and ginger.
6. The compound sepia ink composition according to claim 5, wherein the compound extract is obtained by immersing oyster, licorice, jujube and ginger in water, refluxing and concentrating.
7. The compound cuttlefish ink composition of claim 6, wherein the compound extract comprises raw materials of 5-9 parts of oyster, 1-2 parts of liquorice, 5-9 parts of Chinese date and 1-2 parts of ginger.
8. A method for preparing the compound squid ink composition of any one of claims 5 to 7, which is characterized in that the preparation method comprises the following steps: weighing 5-9 parts of oyster, 1-2 parts of liquorice, 5-9 parts of jujube and 1-2 parts of ginger according to the weight proportion, adding 10 times of water into the mixture to soak for 20min, carrying out reflux extraction for 1h, carrying out total extraction for 2 times, combining the extracting solutions, concentrating the extracting solutions to 1/10 of the volume of the extracting solutions, adding 1 part of cuttlefish ink extract, stirring the mixture at a constant temperature of 40 ℃ for 1h, and preserving the mixture to obtain the cuttlefish ink compound composition.
9. Use of a compound composition of squid ink according to any one of claims 5 to 7 or a compound composition of squid ink according to claim 8 in the preparation of anti-hyperkinetic and anti-depression drugs.
10. The use according to claim 9, wherein the compound composition of sepia is used as an active ingredient, and is mixed with pharmaceutically or food acceptable traditional Chinese medicine decoction pieces, auxiliary materials or auxiliary additives to prepare anti-hyperkinetic and anti-depression drugs.
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