Composition for treating major depressive disorder

A technology of depression and composition, which is applied in the field of composition for treating severe depression, can solve the problems of no curative effect advantage, achieve the effect of reducing dosage and addiction, high treatment efficiency and few side effects

Active Publication Date: 2021-03-23
SHENZHEN SCIENCARE MEDICAL INDUSTRIES CO. LTD.
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] CN106727562A discloses a composition of buprenorphine and μ opioid receptor antagonist for antidepressant treatment. The invention utilizes the characteristics of buprenorphine’s μ opioid agonist and κ receptor blocker, and uses μ opioid receptor antagonist Antibody antagonists such as samitorphine, naltrexone, nalmefene, etc. antagonize μ opioid receptors, because these antagonists have higher affinity than buprenorphine and μ opioid receptors, so buprenorphine can only Antagonizing the κ receptor, the activation of the κ receptor pathway can prevent the up-regulation of the positive effect, and the up-regulation of the positive effect may occur after the antagonism, so as to achieve the therapeutic effect of antidepressant, but the clinical trial product of the invention has shown in the clinical phase III trial Compared with the control drug venlafaxine, there is no obvious curative effect advantage

Method used

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  • Composition for treating major depressive disorder
  • Composition for treating major depressive disorder
  • Composition for treating major depressive disorder

Examples

Experimental program
Comparison scheme
Effect test

experiment example 1

[0047] Experimental Example 1. Efficacy Evaluation of a Composition for the Treatment of Severe Depression

[0048] 1. Experimental animals

[0049] Experimental animals Kunming white mice, body weight 18-22g.

[0050] 2. Animal modeling

[0051] Refer to the construction method of the chronic unpredictable depression mouse model given by SuWJ et al. and Li M et al. to establish the model. The specific operations are as follows:

[0052] The mice were randomly divided into a model group and a normal control group according to body weight. The normal control group had 10 mice. The normal control group was not given any stimulation. The model group was given 7 different chronic stress stimuli within 35 days. Chronic stress stimuli include: ① Water deprivation for 24 hours, ② Fasting for 24 hours, ③ Moist bedding for 24 hours (200 ml of tap water was poured into the rat cage), ④ Tilting of the rat cage (45°, 24 hours), ⑤ Clamping the tail for 1 minute, ⑥ Putting on ice Stimula...

experiment example 2

[0077] Experimental Example 2 Addiction Experiment

[0078] The rats were randomly divided into 11 groups according to body weight (about 150 g), 10 in each group, half male and half male.

[0079] Experimental method: administer three times a day for a total of 30 days. The administration method is as follows: (1) Buprenorphine control group: 0.1mg / kg / time in the first week; 0.2mg / kg / time in the second week; 0.4mg / kg / time in the third week; 22-30 days 0.4mg / kg / time; (2) Dextromethorphan control group: 5mg / kg / time in the first week; 10mg / kg / time in the second week; 20mg / kg / time in the third week; 20mg / kg / time in the 22nd-30th day kg / time; (3) drug group 1-10: 5mg / kg / time in the first week; 10mg / kg / time in the second week; 20mg / kg / time in the third week; 20mg / kg / time in the 22nd-30th day ; Wherein, the administration of drug group 1 is buprenorphine and dextromethorphan with a mass ratio of 1:7.5; the administration of drug group 2 is buprenorphine and dextromethorphan with a...

Embodiment 1

[0099] A nasal inhalation powder for treating severe depression, comprising the following components by weight: 1 part of buprenorphine, 50 parts of dextromethorphan, and 100 parts of auxiliary materials;

[0100] The particle size of the buprenorphine is D10=0.5-30 micron, D50=5-100 micron, D90=10-200 micron; the particle size of the dextromethorphan is D10=0.5-30 micron, D50=5 -100 microns, D90=10-200 microns.

[0101] Preparation method: mix 0.1g buprenorphine and 5g dextromethorphan, add 2.8g microcrystalline cellulose and 7g lactose, then add 0.2g surfactant poloxamer (p188) and 75% ethanol aqueous solution is used as a binder, wet granulated, passed through a 120-mesh sieve for sizing, and the fine particles are dried in an oven at 80°C to obtain the final product.

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Abstract

The invention discloses a composition for treating major depressive disorder. The composition is characterized by comprising buprenorphine active ingredients and dextromethorphan active ingredients, wherein the weight ratio of the buprenorphine active ingredients to the dextromethorphan active ingredients is 1: (7.5-300). Through synergistic compounding of buprenorphine and dextromethorphan, underthe combined action of multiple targets and multiple mechanisms such as activation of mu opioid receptors, antagonism of kappa opioid receptors, antagonism of NMDA receptors, activation of sigma-1 receptors, antagonism of 5-HT receptors and NE receptors, blocking of inflammatory pathways and the like, the composition can greatly improve the treatment effect on patients with major depressive disorder (MDD), and especially with treatment refractory depression (TRD); and meanwhile, the dosage and addiction of the buprenorphine are reduced through the dextromethorphan, and the composition has theadvantages of being multi-target, rapid in effect taking and low in addiction.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical compositions, and in particular relates to a composition for treating severe depression. Background technique [0002] Depression is a common mental illness, with 300 million people worldwide suffering from it, causing serious harm to patients' physical and mental health, quality of life, occupation and social function, and is an important cause of human suicide. Depression has become one of the leading causes of the global burden of disease, reaching $200 billion annually in the United States alone. It is estimated that the social burden of disease caused by depression will rise to the second place after coronary heart disease at the beginning of this century. According to an epidemiological survey conducted in 17 developed countries around the world, one out of every 20 people experienced depression in the past year. At present, the pathogenesis of depression is still unclear, and there...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/485A61K9/72A61K9/20A61K9/08A61P25/24
CPCA61K31/485A61K9/0073A61K9/006A61K9/146A61K9/08A61K9/20A61K9/0043A61P25/24A61K2300/00
Inventor 尹述贵王实强曲伟张桐桐颜携国李勇李远梁民彩
Owner SHENZHEN SCIENCARE MEDICAL INDUSTRIES CO. LTD.
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