CN114404412A

CN114404412A - Application of uncaria active compound in preparation of medicine for preventing and/or treating mental disorder diseases

Info

Publication number: CN114404412A
Application number: CN202210201941.6A
Authority: CN
Inventors: 周文霞; 黄晏; 赵勤实; 张永祥; 彭丽艳; 王陈; 周浩锋; 于琪; 王新悦; 王子元
Original assignee: Kunming Institute of Botany of CAS; Academy of Military Medical Sciences AMMS of PLA
Current assignee: Kunming Institute of Botany of CAS; Academy of Military Medical Sciences AMMS of PLA
Priority date: 2022-03-03
Filing date: 2022-03-03
Publication date: 2022-04-29
Anticipated expiration: 2042-03-03
Also published as: CN114404412B

Abstract

The invention provides an application of an uncaria active compound in preparing a medicine for preventing and/or treating mental disorder diseases, and relates to the technical field of medicine application. The mental disorder disease includes neuropsychiatric disorder caused by traumatic memory. The uncaria active compound of the invention can contain uncarine, isocoumarin, derivatives and isomers obtained by modifying the molecular structure of the active compound, and the like. The active compound of the invention can promote the regression of wound memory and has the functions of preventing and relieving neuropsychiatric disorders (such as posttraumatic stress disorder and phobia) caused by the wound memory.

Description

Application of uncaria active compound in preparation of medicine for preventing and/or treating mental disorder diseases

Technical Field

The invention relates to the technical field of medical application, in particular to application of an uncaria active compound in preparing a medicament for preventing and/or treating mental disorder diseases.

Background

Traumatic events include all events that can cause traumatic memory, such as natural disasters, accidents (e.g., traffic accidents, terrorist events), war, and military operations. Disorders of enhancement or resolution of traumatic event-related memory abnormalities can lead to serious neuropsychiatric disorders such as post-traumatic stress disorder, anxiety, fear, and depression, among others. The cognitive function impairment and mental disorder symptoms of the operating personnel caused by traumatic events such as rescue and disaster relief, military operations and the like can seriously affect the completion of fighting capacity and tasks. The mechanism of the psychopathological phenomenon of traumatic memory is very complex.

At present, the treatment modes such as anxiolytic treatment, antidepressant treatment and sleep improvement are mainly adopted for the diseases, but the curative effect of the medicine is not ideal. Since wound memory is a key central causative factor in these diseases, promoting regression of wound memory is a more desirable therapeutic strategy. However, no drug based on promoting regression of traumatic memory is currently available.

In view of this, the invention is particularly proposed.

Disclosure of Invention

The invention aims to provide application of an uncaria active compound in preparing a medicament for preventing and/or treating mental disorder diseases. The invention discovers that uncaria active compounds (comprising uncarine, isocoumarin, derivatives and isomers obtained by modifying the molecular structures of the active compounds) can promote the regression of wound memory and have the effects of preventing and relieving neuropsychiatric disorders (such as acute stress disorder, post-traumatic stress disorder, phobia, anxiety, depression) and the like caused by the wound memory.

The technical scheme provided by the invention is as follows:

the use of an uncaria active compound in the preparation of a medicament for the prevention and/or treatment of psychotic disorders comprising neuropsychiatric disorders due to traumatic memory.

The invention provides a new application direction of a medicament, and the prior art does not report the effect of uncaria active compounds such as rhynchophylline and isomers thereof on promoting the regression of wound memory. Experiments on the influence of uncaria active compounds on electric shock wound memory prove that the uncaria alkali and the isorhynchophylline can obviously promote the wound memory to be subsided after a wound event, so that the uncaria alkali and the isorhynchophylline can be used for preparing medicines for preventing, relieving and/or treating mental disorder diseases caused by the wound memory.

In one embodiment, the uncaria active compound is selected from one or more of uncarine or derivatives thereof and/or isomers of uncarine or derivatives thereof.

In one embodiment, the isomers of rhynchophylline include one or more of isocoumarine, corynoxine, and corynoxine B.

Ramulus Uncariae cum uncis is a plant of Rubiaceae, and is also a common Chinese medicine, and its main effective components are indole alkaloids including rhynchophylline, isocoumarine, corynoxine B, and corynoxine.

In one embodiment, the medicament further comprises one or more pharmaceutically acceptable excipients.

In one embodiment, the pharmaceutically acceptable excipients include one or more of carriers, excipients, diluents, lubricants, wetting agents, emulsifiers, suspension stabilizers, preservatives, sweeteners, and flavors. For example, pharmaceutically acceptable excipients include, but are not limited to, at least one of lactose, dextrose, sucrose, sorbitol, mannose, starch, acacia gum, calcium phosphate, alginate, gelatin, calcium silicate, fine crystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methylcellulose, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, and mineral oil.

In the present invention, "pharmaceutically acceptable excipients" are substantially synonymous with "pharmaceutically acceptable excipients" understood in the art or "excipients commonly used in pharmaceutical processes", and one skilled in the art can select conventional excipients according to actual conditions and preparation requirements.

In one embodiment, the dosage form of the medicament comprises one or more of granules, capsules, tablets, powders, oral liquids, injections, syrups, lozenges, pills, injections, transdermal preparations. In one embodiment, the drug is administered orally, sublingually, transdermally, intramuscularly, subcutaneously, and the like. The preparation process and equipment for various pharmaceutical preparations with different dosage forms belong to the conventional technology in the pharmaceutical field, and the invention is not limited to the process and equipment.

In one embodiment, the uncaria active compound is obtained by extraction from a plant, such as uncaria, or by chemical synthesis methods. Ramulus Uncariae cum uncis is usually derived from dried stem branch with ramulus Uncariae cum uncis, ramulus Uncariae Macrophyllae, ramulus Uncariae cum uncis, or ramulus Uncariae cum uncis of Rubiaceae, and its main effective component can be obtained by extraction. In addition, the uncaria active compounds can also be synthesized by a chemical synthesis method.

In the invention, the medicament containing the uncaria active compound can obviously eliminate the wound memory after a wound event and can effectively play a role in treating or preventing neuropsychiatric disorder or related diseases caused by the wound memory.

In one embodiment, the neuropsychiatric disorder resulting from traumatic memory comprises a trauma-related stress or post-traumatic stress disorder. Traumatic events can lead to serious neuropsychiatric disorders such as posttraumatic stress disorder (PTSD), which is mainly characterized by invasive experience of traumatic memory, avoidance of trauma-related events, increased negative mood and mental symptoms of high alertness. Wars, military operations, serious accidents, natural disasters, terrorist attacks and the like are all high-risk factors, and particularly, military populations and emergency rescue and relief personnel face more and more serious traumatic events. The trauma-related stress comprises one or more of a trauma memory-related anxiety disorder, a phobia, or depression.

In one embodiment, the regression of wound memory is promoted by administering the drug to the subject.

Trauma-related stress or post-traumatic stress disorder is generally associated with the formation of wound memory and difficulty in resolving. After a patient is subjected to particular dangers or irritations or experiences a catastrophic event, memory may develop that can cause psychological, emotional, and even physiological irregularities, such as associated fear of traumatic memory, causing a handicap in the personality and mental characteristics of the patient. Severe mental trauma has typical symptoms in addition to the above, such as the memory or picture of the traumatic event constantly reappearing in the dream or in the brain, making the victim often unreliably in panic and suffering as if the traumatic event had just occurred. Therefore, accelerating the regression of fear memory is an important way and direction to improve clinical symptoms associated with traumatic memory, including contextual fear, depression, anxiety, and the like. The uncaria active compounds of the present invention can enhance the regression of fear memory.

In one embodiment, the uncaria active compound can be used for preparing a medicament for preventing, treating or relieving the scene fear of the post-traumatic stress disorder.

In one embodiment, the subject refers to an animal, in particular a mammal, preferably a rat, a mouse or a human. In one embodiment, the subject is a mouse.

In one embodiment, the medicament can be used for preparing a medicament for ameliorating glucocorticoid-induced neurosynaptic plasticity damage by administering the medicament to a susceptible human or patient.

In the present invention, the administration of an effective amount of an uncaria active compound of the present invention can prevent and/or treat traumatic-related stress or post-traumatic stress disorder associated with traumatic memory. The term "effective amount" refers to an amount sufficient to obtain, or at least partially obtain, the desired effect. It is within the ability of the person skilled in the art to determine such an effective amount based on the prophylactic or therapeutic requirements, depending on the general conditions of the susceptible population or patient, such as age, weight and sex, and the mode of administration of the drug.

In one embodiment, the medicament may be used in combination with other known medicaments for the treatment of trauma-related stress or post-traumatic stress disorder.

The medicament can be applied together with other treatments, for example, the medicament can be used for preparing auxiliary medicaments for behavior cognition treatment. The invention discovers that the action of promoting the regression of the memory of the wound by combining the behavior cognition therapy and the medicament is stronger than that of singly applying the behavior cognition therapy or the medicament, and the uncaria active compound can be used in combination with the behavior cognition therapy to enhance the curative effect.

For purposes of the present invention, the term "treating" includes inhibiting, delaying, arresting, alleviating, attenuating, limiting, reducing, arresting, reversing, or curing a disease, condition, disorder, injury, or health disorder, the development, process of which is a symptom. Herein, the term "therapy" is understood to be synonymous with the term "treatment". Within the scope of the present invention, the terms "prevent", "preventing" and "prophylaxis" are used synonymously and refer to avoiding or reducing the risk of contracting, developing, suffering or suffering from a disease, condition, disorder, injury or health disorder, such a condition and/or the development or progression of symptoms of such a condition. The treatment or prevention of a disease, disorder, injury, or health problem may be partial or complete.

In the present invention, the medicament prevents, treats or alleviates at least one sign or symptom of post-traumatic stress disorder, e.g., reducing abnormal or anxious behavior, reducing repetitive demonstration of wound-specific replay in terms of expressing a wound.

It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments. Not to be reiterated herein, but to the extent of space.

Compared with the prior art, the invention has the beneficial effects that:

the prior art researches have no direct discovery, and the uncaria active compound can not be logically deduced to have the function of promoting the wound memory to be resolved. On the contrary, in the aspect of influence on learning and memory, a great deal of research shows that the compounds such as rhynchophylline have the effect of enhancing the learning and memory, and the wound memory is also a memory, so that the compounds such as rhynchophylline are used for enhancing the wound memory rather than accelerating the regression of the wound memory. The invention discovers and proves that the rhynchophylline and the isorhynchophylline can obviously promote the regression of the traumatic memory after the traumatic event for the first time through experiments, so that the rhynchophylline and the isorhynchophylline can be used for preparing the medicine for preventing and/or treating the mental disorder diseases caused by the traumatic memory (the new application of the active compound of the rhynchophylline is discovered);

the uncaria active compound has the effect of promoting the regression of the traumatic memory in animal experiments, and has prevention and/or treatment effect on neuropsychiatric disorder caused by the traumatic memory; the invention proves that the uncaria active compound has the following effects: (1) improving glucocorticoid-induced plastic impairment of the synapse; (2) the direct administration can promote the regression of the wound memory (3) and the behavior cognition therapy are combined, and the effect of promoting the regression of the wound memory is better than that of singly using the behavior cognition therapy or uncaria active compound.

The uncaria active compound is applied to the neuropsychiatric disorder caused by wound memory, has the advantages of small side effect, good safety and long-term use, and has good medicinal prospect; the invention can adopt uncaria active compounds with single effective components to prepare the medicine, and can also adopt 2 or more effective components to prepare the medicine together.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and other drawings can be obtained by those skilled in the art without creative efforts.

FIG. 1 is a graph of the effect of an uncaria active compound on corticosterone-induced synaptic plasticity (LTP) impairment;

FIG. 2 is a flow chart of experiments on the regression effect of uncaria active compounds on wound memory (A is an experiment flow chart of the regression effect on wound memory when used alone, B is an experiment flow chart of the regression effect on wound memory when used in combination with behavior cognition therapy);

FIG. 3 is a graph of the effect of Uncaria active compound on wound memory on day 2 post-shock;

FIG. 4 is a graph of the effect of Uncaria active compound on wound memory on day 30 post-shock;

FIG. 5 is a graph of the effect on post-shock day 2 traumatic memory in combination with behavioral cognitive therapy;

figure 6 is a graph of the effect on wound memory on day 30 post-shock, used in combination with behavioral cognitive therapy.

Detailed Description

The technical solutions of the present invention will be described clearly and completely with reference to the following embodiments, and it should be understood that the described embodiments are some, but not all, embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products commercially available.

Example 1:

1.1 reagents and materials used for the experiment:

c57 mouse, male, 4-6 weeks, 18 + -2 g body weight, clean grade, Sibefu (Beijing) Biotechnology, Inc. The temperature (25 +/-1 ℃) and the humidity (50 +/-5%) of the animal breeding environment can be freely taken and drunk, and the daily illumination/darkness is 12 hours respectively.

Rhynchophylline and isocoumarin were provided by Kunming plant research institute of Chinese academy of sciences.

1.2 Experimental procedures

After the mice experience the traumatic event, the fear behavior can be shown to the environment and clues related to the traumatic event, and the fear behavior of the animals is obviously reduced after the rhynchophylline and the isorhynchophylline are given.

Test example 1: effect on glucocorticoid-induced synaptic plasticity impairment

Increased levels of glucocorticoids can result from traumatic stress, and high levels of glucocorticoids are believed to be important factors in slowing or strengthening the regression of wound memory. In the experiment, the influence of uncaria active compounds on synaptic plasticity damage caused by glucocorticoid (corticosterone) is examined, long-term potentiation (LTP) is one of main functional indexes of synaptic plasticity, and the LTP is used as an index to react on the synaptic plasticity in the experiment.

(1) Experimental Environment

The whole experiment process is carried out in the environment with the temperature of 25 +/-1 ℃, the humidity of 55 +/-5 percent and the humidity of below 60 decibels, and the body temperature of the mouse is ensured by a body temperature maintenance instrument.

(2) Experiment grouping

Mice were randomly grouped after weighing, blank, model and drug intervention groups, respectively. Distilled water is given to the blank group and the model group through intragastric gavage;

the pharmaceutical intervention groups were given 3 different doses of rhynchophylline and isorhynchophylline, respectively. In the drug intervention group, corticosterone is injected subcutaneously 1h before HFS, and 20/40/80mg/kg of rhynchophylline or isocoumarin is injected once 30min before corticosterone injection;

model group (CORT group), corticosterone was injected subcutaneously 1h before HFS.

(3) Brain region localization

After the mice were fully anesthetized by intraperitoneal injection of 20% urethane (1.6 g/kg), the heads of the mice were fixed on a brain stereotaxic apparatus using ear rods, and the heads were kept horizontal without affecting the normal breathing of the mice. The scalp of the mouse was then cut open using an ophthalmic surgical scissors, exposing the skull, positioning the cell layer of the particles of the penetrating fiber (PP) and Dentate Gyrus (DG) with the bregma as the origin, PP positioning parameters 3.8mm posterior to bregma, 3.0mm lateral to the midline, and depth 1.5mm under the dura; the granular cell layer location parameter of DG region was 2.0mm posterior to bregma, 1.4mm lateral to midline, and 1.5mm under dura mater. Drilling holes at the positioning points of the PP area and the DG area by using a skull drill, wherein the diameter of the drill is 1.2mm, the holes are not bleeded as much as possible in the drilling process, the stimulating electrode is inserted into the PP area, the recording electrode is inserted into the DG area, and the reference electrode is clamped on the scalp.

(4) Group peak potential recording

After the electrodes were inserted, the stimulator parameters were adjusted with the wave width set to 100 μ s and the current set to 0.3mA for evoked group spike (PS). After the PS is stabilized, the stimulation current is adjusted to reduce the PS to about 1/3-1/2 of the original value. Stabilization was continuously recorded for 30min as baseline value, followed by high frequency stimulation (HFS, 400Hz, 100 times) to induce LTP (long term enhancement) given through fiber (PP), and PS values were recorded for the following 1 h. The recorded signals in the experiment are amplified by a microelectrode amplifier (low-pass filtering is 1KHz, gain is 10), then are converted into digital signals by a digital-to-analog converter, and finally, an Excel data sheet is automatically generated by collecting and analyzing WinLTP software (Britistol university, England).

(5) Observation index and measurement method

Relative value (%) of PS was used as an index; the PS value after HFS or LFS was compared to the baseline value obtained after 30min of percentage differentiation (i.e., 100%) to obtain the relative values of the individual PS values.

Test example 2: effect of Uncaria active Compounds alone on regression of wound memory

The adopted method comprises the following steps:

(1) environmental adaptation

Within 7 days of acclimatization, mice were gently grabbed for 3 minutes each day in order to reduce the effect of irrelevant stress stimuli on subsequent experimental manipulations. In the experimental process, the relative silence of the experimental environment is ensured.

(2) Experiment grouping

After weighing, the mice were randomly divided into a blank group, a model group (CORT group), and a drug intervention group, and each group had 20-24 animals in the behavioral experiments. Distilled water is given to the blank group and the model group through intragastric gavage; the drug intervention group comprises 2 groups (rhynchophylline and isocoumarin), and is injected into the abdominal cavity immediately after electric shock stress, and the dosage of the monomer compound is 40mg/kg (the experimental flow is shown as A in figure 2).

(3) Autonomic activity test

Opening the computer and the spontaneous activity instrument, and closing the doors of all spontaneous activity boxes; the anymaze software was opened, the autonomously mobile experimental templates were loaded, and the experimental names, groups, and animal numbers were added to the experimental setup. Half an hour before the start of the autonomic activity experiment, the mice were moved to the laboratory and acclimated for at least 30 minutes. During the experiment, the sound is prohibited, and the walking is prohibited. The size of the autonomous activity box is 30cm multiplied by 30cm which is made of black polyethylene plates. The mouse was gently placed into the autonomous mobility box and the box door closed. Parameters such as total free movement distance and average speed of each mouse in the box within 20 minutes were recorded using anymaze software and a video acquisition system. After each mouse experiment, the box was wiped with 75% alcohol to avoid odor interference.

And (3) observation indexes are as follows: total distance of movement of mice.

(4) Acute shock stress in mice

Mice were acclimated in shock ac box a for 5min one day prior to acute stress with white noise 60dB throughout. During stress, the mice are placed in the electric shock alternating current box A to adapt for 3 minutes, and are given a string of continuous multiple foot bottom electric shocks to the other mice except for a control group, wherein the sound stimulation is carried out for 20s (5000Hz and 78dB), the foot bottom electric shock lasts for 1.5mA and 2s, the process is repeated for 5 times, each time interval is 60s, and the whole process is white noise (60 dB).

(5) And (3) detecting wound memory: wound memory detection was performed on days 2 and 30 post-shock, respectively

And (3) scene memory: mice were replaced in ac box a for 5 minutes with full white noise (60 dB). The AC box environment was completely consistent with that of mice under stress. Measurement indexes are as follows: the time of rigor mortis.

And (3) thread memory: the mice were acclimated for 3 minutes after being placed in the shock ac box C, given a sound stimulus for 20s (5000Hz, 78dB)1 time, and after 30s were returned to the mouse cage with white noise (60dB) throughout. Measurement indexes are as follows: the time of rigor mortis.

Test example 3: effect of traumatic memory regression in combination with behavioral cognitive therapy

The experimental procedure in this section was the same as in test example 2. However, before administration, mice were acclimated in an ac box for 3min, acoustically stimulated for 20s (5000Hz, 78dB), repeated 20 times with 30s intervals, with white noise throughout (60dB), and behavioural cognitive therapy (experimental procedure shown in fig. 2, panel B) simulated psychotherapy.

All data were expressed as "mean ± sem", and all data analysis and graphical fabrication were performed using GraphPad Prism 8.0 software. The Student's t-test is adopted for comparison between the model and the control; the mean size between the administration group and the model group was compared by using one-way analysis of variance following by Dunnett's multiple composition test; PTSD incidence was analyzed for data significance using the chi-square test. P <0.05 was considered statistically poor.

Analysis of test results

1. Effect of Uncariaine and Isorhynchophylline on LTP injury caused by corticosterone

In test example 1, single gavage of 20mg/kg and 80mg/kg of rhynchophylline did not improve LTP injury caused by corticosterone, and 40mg/kg of rhynchophylline significantly improved LTP injury caused by corticosterone (see fig. 1, a and B); 20mg/kg of isorhynchophylline subjected to single intragastric administration has no improvement effect on LTP injury caused by corticosterone, and 40mg/kg and 80mg/kg of isorhynchophylline have obvious improvement effects on LTP injury caused by corticosterone (see C and D in figure 1).

FIG. 1 shows the active compounds of Uncaria rhynchophyllaEffects on LTP damage caused by corticosterone. P<0.001, compared with normal group, t test;^#P<0.05，^###P<0.001, one-way analysis of variance and Dunnett's test, mean ± standard error, n ═ 5, compared to CORT (corticosterone) group. A. Relative to the PS amplitude change curve, subcutaneously injecting corticosterone 1h before HFS, and performing single intragastric administration of 20/40/80mg/kg rhynchophylline 30min before corticosterone injection; B. the effect of uncarine with different doses in single intragastric administration on LTP injury caused by corticosterone; C. relative to the PS amplitude change curve, subcutaneously injecting corticosterone 1h before HFS, and performing single intragastric gavage of 20/40/80mg/kg of isocoumarin 30min before corticosterone injection; D. the effect of isorhynchophylline with different doses in single intragastric administration on LTP injury caused by corticosterone.

The protective effect of rhynchophylline and isocoumarin on LTP injury caused by corticosterone is shown, and single intragastric gavage of rhynchophylline and isocoumarin has obvious improvement effect on LTP injury caused by corticosterone. Suggesting that it may have a beneficial effect on wound memory. The results in this section indicate that 40mg/kg is the most effective, so the subsequent experiments were performed using a dose of 40 mg/kg.

2. Effect of Uncariaine and Isorhynchophylline on wound memory regression on day 2 post traumatic event

In experimental example 2, the trauma event simulated by electric shock can significantly increase the rigor time of the animals in the test of situational memory and clue memory, and prompt the formation of the trauma memory; rhynchophylline and isocoumarin significantly promoted the regression of wound memory on day 2 after the traumatic event. The results are shown in FIG. 3, where P<0.05，**P<0.01，***P<0.001, compared to a normal control group; # P<0.05，^##P<0.01，^###P<0.001 and model group comparison, mean ± sem, n-20-24. It is shown that rhynchophylline and isocoumarin can significantly promote wound memory regression on day 2 after a traumatic event.

3. Effect of Uncariaine and Isorhynchophylline on wound memory regression on day 30 post traumatic event

In experimental example 2, the animals also significantly increased the rigor-than time in the situational memory and clue memory tests 30 days after the shock-simulated trauma event, suggesting that trauma memory could be maintained for at least 30 days without intervention; rhynchophylline and isocoryneBoth the ampelopsin significantly promoted the regression of wound memory on day 30 after the traumatic event. The results are shown in FIG. 4. P<0.05,**P<0.01,***P<0.001 compared to a normal control group;^#P<0.05，^##P<0.01 compared with the model group, mean ± sem, n is 20-24. It is shown that rhynchophylline and isocoumarin can significantly promote wound memory regression on day 30 after a traumatic event.

4. Effect of combination with behavioral cognitive therapy on post-traumatic event day 2 traumatic memory regression

After 30min of traumatic stress, the mice are put back to the trauma different environment for wound environment reappearance, and the drug administration is carried out 2h after the wound environment reappearance, and the effect of the rhynchophylline and the isorhynchophylline on the regression of the wound memory is observed. On the 2 nd day after the electric shock simulated trauma event, the fear of the mouse situation can be obviously improved compared with the rhynchophylline and the isorhynchophylline in the situation fear test and the fear of the mouse situation can be improved compared with the rhynchophylline and the isorhynchophylline in the simulated psychological treatment group; rhynchophylline and isorhynchophylline tended to improve clue fear in the clue fear test in mice (see figure 5).

5. Effect of combination with behavioral cognitive therapy on wound memory regression on day 30 post traumatic event

After 30min of traumatic stress, the mice are put back to the trauma different environment for wound environment reappearance, and the drug administration is carried out 2h after the wound environment reappearance, and the effect of the rhynchophylline and the isorhynchophylline on the regression of the wound memory is observed. Rhynchophylline and isorhynchophylline tended to improve clue fear in the cord fear test 30 days after the shock-simulated trauma event (see figure 6).

The results of the test examples show that the uncaria active compound can not only promote the regression of wound memory, but also prompt that the uncaria active compound can be used for promoting the regression of wound memory and relieving related neuropsychiatric disorder; different alkaloids have different action strengths on different indexes, which indicates that the combination of 2 or more than 2 alkaloids possibly has better prevention and treatment effects; the effect of promoting the regression of the traumatic memory is stronger when the composition is used with behavior cognition therapy, and the composition is suggested to be used as an adjuvant drug of the behavior cognition therapy.

Finally, it should be noted that: the above embodiments are only used to illustrate the technical solution of the present invention, and not to limit the same; while the invention has been described in detail and with reference to the foregoing embodiments, it will be understood by those skilled in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some or all of the technical features may be equivalently replaced; and the modifications or the substitutions do not make the essence of the corresponding technical solutions depart from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. Use of an uncaria active compound for the preparation of a medicament for the prevention and/or treatment of psychotic disorders, characterized in that said psychotic disorders comprise neuropsychiatric disorders due to traumatic memory.

2. Use according to claim 1, characterized in that the uncaria active compound is selected from one or more of uncaria rhynchophylla alkali or derivatives thereof and/or isomers of uncaria rhynchophylla alkali or derivatives thereof.

3. The use according to claim 2, wherein the isomers of rhynchophylline comprise one or more of isocorynine, corynoxine and corynoxine B.

4. The use according to any one of claims 1 to 3, wherein the medicament further comprises one or more pharmaceutically acceptable excipients.

5. The use according to claim 4, wherein the pharmaceutically acceptable excipient comprises one or more of a carrier, an excipient, a diluent, a lubricant, a wetting agent, an emulsifier, a suspension stabilizer, a preservative, a sweetener, and a flavoring.

6. The use according to any one of claims 1 to 3, wherein the medicament is in a dosage form comprising one or more of granules, capsules, tablets, powders, oral liquids, injections, syrups, lozenges, pills, injections, transdermal preparations.

7. Use according to any one of claims 1 to 3, wherein the uncaria active compound is obtained by extraction from plants or by chemical synthesis.

8. The use according to any one of claims 1 to 3, wherein the neuropsychiatric disorder due to traumatic memory comprises a trauma-related stress or post-traumatic stress disorder.

9. The use according to claim 8, wherein the trauma-related stress comprises one or more of a trauma memory-related anxiety disorder, a phobia.

10. The use of any one of claims 1 to 3, wherein the regression of wound memory is promoted by administering the medicament to the patient.