阅读说明：本技术 巴利森苷a在治疗缺陷多动障碍的医疗用途 (Medical application of balamin A in treating deficiency hyperactivity disorder ) 是由 徐天瑞 邢其郡 杨洋 赵娅 郭静 于 2021-01-27 设计创作，主要内容包括：本发明公开了巴利森苷A用于制备治疗缺陷多动障碍病的药物的用途。即巴利森苷A可用于制备治疗缺陷多动障碍的药物,且效果优异。(The invention discloses an application of balamin A in preparing a medicament for treating deficiency and hyperactivity. The balamin A can be used for preparing the medicine for treating the deficiency hyperactivity disorder and has excellent effect.)

1. The use of the barban glycoside A in preparing a medicament for treating the deficiency hyperactivity disorder.

2. A pharmaceutical composition comprising the barbaloin a or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable carrier thereof of claim 1.

3. A pharmaceutical which is a lyophilizate, a tablet, a granule or a capsule, characterized in that said pharmaceutical is an injection, a lyophilizate, a tablet, a granule or a capsule comprising the pharmaceutical composition of claim 2.

Technical Field

The invention mainly relates to the field of medicines, in particular to medical application of barbaloin A in treating deficiency hyperactivity disorder.

Background

Attention Deficit Hyperactivity Disorder (ADHD), commonly known as infantile hyperactivity disorder, has been affected by genetics, nerves, immunity, environment, society and other aspects in recent years, resulting in neurological development and psychobehavioral disorders in children with an increasingly high incidence. The symptoms of the disease are mainly hyperactivity, inattention, social disturbance and the like which are not matched with age. ADHD has a prevalence of about 6.3% in our country, with boys more likely to develop the disease than girls, and over half of the pediatric symptoms persist to adulthood.

Many studies now demonstrate that the pathogenic mechanism of ADHD may be related to the disturbance of monoamine neurotransmitters in the brain, mainly including Dopamine (DA), 5-hydroxytryptamine (5-HT), Norepinephrine (NE), etc. Wherein defects in DA anabolism are now widely recognized as the major cause of ADHD pathogenesis. While the 5-HT system is associated with cognitive impulses and emotions, which can cause impulses, attacks, hyperactivity and the like if transmitter transmission is abnormal.

Currently, most of ADHD medicines are central stimulants, antidepressant medicines and the like, the main medicines are methylphenidate and tomoxetine, but the adverse reactions are more, the recurrence rate is high after medicine withdrawal, and a lot of troubles are caused in the acquisition and management of the medicines as a tube medicine.

Over 10 years, the research on Chinese medicaments for treating the attention deficit hyperactivity disorder in China is more and more intensive, and the Chinese medicaments are important means for health preservation and treatment for thousands of years and make great contribution to the prosperity of Chinese nation. Rhizoma gastrodiae is a traditional Chinese medicine, is a perennial parasitic plant, and has been used as a medicine for more than two thousand years. Hemp was originally recorded in the Shennong herbal meridians in the warring state and the Qin-Han period. In this monograph, gastrodia elata is classified as a "top-grade" drug that has a revitalizing effect, is non-toxic, and therefore harmless for long-term use. Rhizoma Gastrodiae has wide biological and pharmacological effects, and its components have neuroprotective, antiinflammatory, and antioxidant effects, so the components of rhizoma Gastrodiae have tranquilizing, anticonvulsant, anxiolytic, and depressive effects.

Many chemical components have been isolated from gastrodia elata so far, and recent studies have confirmed that phenolic substances present in gastrodia elata are considered as main active components, and gastrodin and barcinoside having gastrodin as a structural unit are the main blood-entering active components. The method selects the barbaloin A (PA) in the barbaloin as a research object, and researches the drug effect and toxicology test of the barbaloin A on the treatment of the hyperactivity disorder. The experiment uses the spontaneous activity of mice as the main index to research the pharmacodynamic action, and uses the indexes of inflammatory factors of brain, kidney, liver and spleen, conventional white blood cells, platelets and the like to observe the toxic effect of PA on various organs of the body.

Disclosure of Invention

In order to solve the defects in the prior art, the invention provides the medical application of the barbaloin A in treating the defective hyperactivity disorder, namely the barbaloin A can be used for preparing a medicine for treating the defective hyperactivity disorder and has excellent effect.

The inventor finds that the balsamoside A can effectively reduce spontaneous movement on the premise of not influencing the levels of central serotonin and dopamine in the pharmacological activity research of the balsamoside A, plays an important role in organisms including human bodies which do not need to solve the problem of hyperpsychiasm but have excessive spontaneous movement, and is used for treating the deficiency hyperactivity disorder.

The invention also provides a pharmaceutical composition, which comprises the above-mentioned Balisenside A or its medicinal salt or its medicinal carrier.

The invention also provides a medicine which is a freeze-dried preparation, a tablet, a granule or a capsule, and the medicine is an injection, the freeze-dried preparation, the tablet, the granule or the capsule comprising the pharmaceutical composition.

Drawings

FIG. 1 is a graph showing the effect of PA on spontaneous activity in mice.

FIG. 2 is a graph showing the effect of PA on 5-HT and DA in the brain.

Fig. 3 is a graphical representation of the effect of PA on sleep latency and duration.

FIG. 4 is a graph showing the effect of PA on inflammatory factors of heart, liver, spleen and kidney.

FIG. 5 is a graph showing the effect of PA on inflammatory factors of heart, liver, spleen and kidney.

FIG. 6 is a graph showing the effect of PA on red, white, platelets and lymphocytes in a blood routine.

FIG. 7 is a graph showing the effect of PA on red, white, platelets and lymphocytes in a blood routine.

FIG. 8 is a third graph showing the effect of PA on red, white, platelets, and lymphocytes in a blood routine.

Detailed Description

The present invention will be further described with reference to specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Further, it should be understood that various changes or modifications of the present invention may be made by those skilled in the art after reading the teaching of the present invention, and such equivalents may fall within the scope of the present invention as defined in the appended claims.

Example 1: the balaneboside A can obviously reduce spontaneous movement and treat hyperactivity disorder

1. Biological material

Mice, used in the examples, were provided by the SPF laboratory animal center, university of Kunming medical, and were kept under standard laboratory conditions (temperature 25. + -. 2 ℃, 12h light/12 h dark). During the study period, the required food and water were provided and after 1 week of acclimation, the mice were randomized into two groups, one control group and one treatment group of balisonin a (pa), this example consisting of 6 mice per group. All tests were performed according to the university of Kunming animal Experimental guidelines. The protocol was approved by the institutional animal care and use committee of university of Kunming university.

2. Drugs and reagents

Balaneboside a (pa) was purchased from medea;

pentobarbital sodium was purchased from Shanxi Asia chemical Co., Ltd, and a reverse transcription Kit (Revertaid Fist Strand cDNA Synthesis Kit) was purchased from Saimer Fei Bio Inc.

All reagents used in the assay were analytically pure.

3. Treatment of

The mice in the control group and the treated group were administered with the barcinoside a and the physiological saline nasally for 8 days, respectively, or alternatively 30 minutes before the exercise activity test or the administration of the sodium pentobarbital. Pentobarbital sodium was dissolved in physiological saline and 42mg/kg (i.p.) was used as the hypnotic agent.

The group A of the Balison glycosides was administered with Balison glycoside A (drug dose 10mg/kg, drug concentration 20mg/ml, e.g. 20. mu.l for 40g nasal mice). Nasal administration step: the head of the mouse is fixed by one hand, the other hand sucks the required volume by a liquid-transferring gun and slowly drops the volume to the nostril of the mouse, the two nasal cavities drop by turns, and the nasal cavity drops the other nasal cavity after absorbing the volume, and the volume is not more than 20 mul as much as possible.

4. Spontaneous locomotor activity test

The sedative effect of balamin a (pa) was assessed by measuring spontaneous locomotor activity in mice. After the nasal cavity injection of PA and normal saline for 15-20 minutes, the mice are respectively placed in a kinetic energy tester.

The exercise capacity and the number of times of standing can be calculated using a YLS-1A exercise capacity tester (Jinan Yiyan science and technology development Co.) consisting of five connected transparent cells and five infrared sensors. A small amount of padding is put into each detection chamber, and the mice are put into the chambers to adapt for 5-10 minutes and then start to perform activity counting. After the start of the recording, the activity count was increased for each mouse movement in the chamber, and the number of mouse activities within 2 hours after nasal administration was recorded. After each test, the tester housing is preferably thoroughly cleaned with 70% ethanol. The test results are shown in FIG. 1.

5. Pentobarbital sodium induced sleep test

Pentobarbital sodium injection experiments were performed between 9:00 am and 5:00 pm, and the sleep time of each mouse was observed after pentobarbital sodium injection. When the mice lost righting reflex disappeared, they were considered to be in a sleeping state.

The righting reflex is defined as the inability of a mouse to self-right when placed in a dorsal decubitus position for at least 30 seconds. The reflex from administration of sodium pentobarbital to loss of the righting reflex is recorded as sleep latency. And the time from disappearance of righting reflex to recovery was recorded as the sleep duration. The test results are shown in FIG. 3.

RT-PCR experiment

The mouse is killed by cervical dislocation, blood is taken from eye socket of the mouse, eyeball is taken by tweezers, and the blood flows into EP tube from the eye socket. Then, the abdominal organs and the brain and scalp of the mouse are cut off by surgical scissors, about 0.1g of the brain, the heart, the spleen, the kidney and the liver of the mouse are picked up respectively, and the mouse is immediately put into a refrigerator at the temperature of 80 ℃ below zero for storage.

7. Dopamine (DA) and serotonin (5-HT) detection

Mice were sacrificed by cervical dislocation, whole brain homogenate of about 0.1g was taken, 1g tissue was added with 9ml of PBS, and specimens were homogenized thoroughly by hand or by a homogenizer. The supernatant was collected by centrifugation for about 20 minutes (3000 rpm 2000). The DA and 5-HT neurotransmitter levels in the brains of the mice to be tested were used by the elisa method (elisa kit, commercially available from Shanghai enzyme-linked biosciences). The test results are shown in FIG. 2.

8. Routine blood test

The mouse is placed in a 4-degree refrigerator for storage after blood is taken, and a blood sample feeding conventional detector detects various conventional indexes of the mouse blood. The test results are shown in FIGS. 6 to 8.

9. Detecting expression of related genes

Taking the whole brain, spleen, liver and kidney of a mouse, cracking by using Trizol 1mL, extracting total RNA by using a reagent, and then performing reverse transcription to obtain cDNA for RT-PCR experiment detection of the expression of related genes at the RNA level. The test results are shown in FIGS. 4-5.

The results of mouse ethology prove that pa obviously reduces spontaneous movement, the levels of whole brain serotonin and dopamine are not changed, and inflammatory factors of heart, liver, spleen and kidney are not changed, which indicates that the internal organs are not damaged. Therefore, the balsamoside A can reduce spontaneous movement without affecting the level of serotonin and dopamine in the center, and can be used in organisms including human bodies which do not need to solve the problem of hyperpsychosis but have excessive spontaneous movement, and can be used for treating the deficiency hyperactivity disorder.

The above description is only a preferred embodiment of the application and is illustrative of the principles of the technology employed. It will be appreciated by a person skilled in the art that the scope of the invention as referred to in the present application is not limited to the embodiments with a specific combination of the above-mentioned features, but also covers other embodiments with any combination of the above-mentioned features or their equivalents without departing from the inventive concept. For example, the features described above have similar functions to (but are not limited to) those disclosed in this application.