WO2018192428A1 - Application of fully carboxylated osteocalcin in preparing fast-acting antidepressant - Google Patents

Abstract

An application of fully carboxylated osteocalcin in preparing a fast-acting antidepressant. The fully carboxylated osteocalcin is administered at a concentration of 80 ng/g.

Description

Application of fully carboxylated osteocalcin in the preparation of rapid antidepressants Technical field

The invention relates to the field of medicine, in particular to a novel fast acting antidepressant.

Background technique

Drug treatment is currently the main means of treatment for depression. Most of the antidepressants currently used are designed based on the monoamine hypothesis of depression, and exert an antidepressant effect by increasing the concentration of monoamine neurotransmitters in the synaptic gap of the central nervous system and enhancing the function of monoamine neurons. Since the 1950s, the development of antidepressants has made great progress. The new generation of antidepressants has been greatly improved in terms of side effects, but its clinical efficacy has not made a substantial breakthrough. There are still many Limitations. Mainly manifested in: 1 clinical slow-acting, there is a delay effect, generally taking antidepressants for 2-3 weeks before clinical effect. 2 The treatment response rate is low, and only 1/3 of the patients with depression are effective for the first antidepressant treatment. 3 drug resistance is obvious, refractory depression has become a major problem in the treatment of depression. 4 increase the risk of suicide in patients with depression, especially in adolescent patients. These limitations lead to extremely low compliance in the treatment process for patients with depression, which makes it difficult to restore the physical function and social function of the patient, and brings a heavy economic burden to the family and society. It can be seen that the drug treatment of depression faces a huge dilemma, and it is urgent to find a new treatment plan for depression.

Osteocalcin, an important component of the extracellular matrix of bone, is the most abundant non-collagen protein in bone. Osteocalcin is an endocrine-regulating hormone involved in the regulation of energy metabolism, male fertility and brain development.

Summary of the invention

In view of this, it is an object of the present invention to demonstrate the use of a rapidly acting antidepressant, fully carboxylated osteocalcin, in the preparation of a rapid antidepressant. This will provide a new theoretical basis for the development of a new generation of antidepressants with fast acting, good safety and good curative effect.

The present invention provides a fast acting antidepressant comprising fully carboxylated osteocalcin.

In the present invention, after intraperitoneal injection of 80 ng/g of fully carboxylated osteocalcin for 30 minutes, the mice exhibited rapid antidepressant effects, and the forced swimming and tail suspension experiments were significantly reduced compared with the normal control group. This provides the basis for the development of new rapid antidepressants.

DRAWINGS

Figure 1 is a graph showing the results of forced swimming experiments;

Figure 2 is a graph showing the results of the suspension tail experiment.

detailed description

The effect of the fully carboxylated osteocalcin of the present invention will be further illustrated by specific experiments below.

1. Experimental animals: Adult male C57BL/6 mice, each weighing an average of 22-25 g. Adaptive feeding was performed in the first two weeks without specific pathogen free experimental animals (SPF).

3. Main reagents: 80 ng/g carboxylated osteocalcin, 30 mg/kg ketamine and physiological saline.

4. Experimental design

Six-week-old male C57BL/6 mice were randomly divided into five groups, including saline (negative control, n=20), three groups of fully carboxylated osteocalcin (n=20 per group), and ketamine. Group (positive control, n=20). Dosing concentration: The concentrations of osteocalcin in the three groups of fully carboxylated osteocalcin groups were 8 ng/g, 20 ng/g and 80 ng/g, respectively, and the concentration of ketamine was 30 mg/kg. Each group was intraperitoneally injected - six times in two days, and behavioral (forced swimming, tail suspension test) was evaluated 30 minutes after the sixth administration. All behavioral records use the Video Surveillance System (SMART).

Forced swimming: The test was conducted for a total of 6 minutes: the first minute was the water adaptation phase; the second minute was 5 minutes from the second minute, and the number of times the two groups of mice remained in the water at rest and the total duration of the duration were calculated for 5 minutes. The longer the time, the longer the immobility time, the stronger the desperation and helplessness of the mice, which means that the depressive symptoms of the mice are more serious.

Suspension test: Before each experiment, the inner wall of the suspension box was scrubbed with chlorine dioxide disinfectant and 75% alcohol. The tail of the mouse was fixed with tape, and the head of the mouse was hung downward. The hanging point of the tail of the mouse was 50 cm away from the experimental table. After 1 minute of adaptation, the accumulated time of the mouse within 5 minutes after recording was recorded.

Experimental result

Referring to Figure 1, forced swimming behavioral results suggest that the immobility time of 80 ng/g fully carboxylated osteocalcin mice was significantly lower than that of the normal control group compared with the saline group (p<0.05). Control group: saline group; cOCN (8 ng/g) group: 8 ng/g fully carboxylated osteocalcin group; cOCN (20 ng/g) group: 20 ng/g fully carboxylated osteocalcin group; cOCN (80 ng/g) Group: 80 ng / g fully carboxylated osteocalcin group; ketamine group: ketamine group. This indicates that 80 ng/g fully carboxylated osteocalcin has a rapid antidepressant effect.

Referring to Figure 2, the results of the tail suspension experiment indicated that the immobility time of 80 ng/g fully carboxylated osteocalcin mice was significantly lower than that of the normal control group (p<0.05). Control group: saline group; cOCN (8 ng/g) group: 8 ng/g fully carboxylated osteocalcin group; cOCN (20 ng/g) group: 20 ng/g fully carboxylated osteocalcin group; cOCN (80 ng/g) Group: 80 ng / g fully carboxylated osteocalcin group; ketamine group: ketamine group. This indicates that 80 ng/g fully carboxylated osteocalcin has a rapid antidepressant effect.

Claims (3)

The use of fully carboxylated osteocalcin in the preparation of rapid antidepressants. The use of fully carboxylated osteocalcin according to claim 1 for the preparation of a rapid antidepressant, characterized in that said fully carboxylated osteocalcin is administered at a concentration of 80 ng/g. A fast-acting antidepressant characterized in that the rapid antidepressant comprises fully carboxylated osteocalcin.

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