Patent Backgrounder on "5-Methyltetrahydrofolate Compositions for Sleep Improvement Applications

Patent Backgrounder on "5-Methyltetrahydrofolate Compositions for Sleep Improvement Applications

Technical Field
The present invention belongs to the field of medicine, specifically, the invention relates to new sleep improving effects of 5-methyltetrahydrofolate
and its use in combination with γ-aminobutyric acid, etc.

Background Technology of the Invention Patent
Insomnia is an important public health problem that requires effective diagnosis and treatment, but the physiological mechanisms of sleep have not been fully elucidated, resulting in a lack of relevant information.
mechanisms have not been fully elucidated, resulting in slow progress in the development of relevant drugs as well as the absence of good treatments for insomnia in clinical practice. Insomnia can be broadly classified into short-term and long-term chronic insomnia (usually lasting several months or years). Epidemiological studies show that 10% to 15% of adults suffer from chronic insomnia, with a higher prevalence among women, and chronic insomnia is present in about 40% of the elderly and people with psychiatric disorders. Chronic insomnia has a significant impact on people's daytime lives, including memory loss, poor concentration, severe disruptions to work as well as school, and increased risk for drivers and the elderly of accidental falls. Not only that, but chronic insomnia can also cause serious damage to human health, including decreased immune function, continued impairment of the patient's psychological state, and increased sensitivity to pain and noise.

There are various causes of chronic sleep disorders, some of which are caused by chronic diseases, including
Rhinitis, sinusitis, allergies, cancer, arthritis, chronic back pain, headaches, breathing difficulties due to diseases of the lungs, nocturia due to urinary disorders, mental illness depression, Parkinson's disease, epilepsy, etc. Unless the main cause of the sleep disorder is successfully diagnosed and corrected, the treatment of insomnia is limited. And unfortunately the chronic diseases described are often not treatable and correctable in a short period of time based on the current level of treatment, and many chronic diseases stay with the patient for a long time, some even requiring lifelong medication to control the symptoms. Another part of the causes of chronic sleep disorders include the patient's metabolic disorders, mental illness, and mental health conditions, for which psychological interventions are needed. Due to the current situation in developing countries, including China, such as the imperfect medical system related to mental health, the small number of related practitioners, and the difficulty of some residents to afford mental health treatment and services, as well as the lack of awareness of related treatment and counseling services, many patients do not receive psychological counseling treatment, including relaxation therapy and cognitive behavioral therapy. Non-pharmacological treatments require long-term adherence to have a significant effect on sleep improvement, lasting from months to years, which also leads to a significant decrease in patient compliance.
This also leads to a significant decrease in patient compliance.

According to an epidemiological statistical study (Chen TY , Winkelman JW , Mao WC , Yeh CB , Huang SY , Kao TW , Yang CC , Kuo TB , Chen WL . Short sleep duration is associated with increased serum homocysteine: insights from a national survey . J Clin Sleep Med . As described in (2019;15(1):139-148), high homocysteine levels are highly correlated with sleep duration less than 5 hours, with an OR of 1 .357 in men and up to 2 .691 in women.It has been shown that homocysteine damages the blood-brain barrier of the brain, leading to increased blood-brain barrier permeability, but homocysteine and insomnia It is not clear who is the cause and who is the effect of the two.

Currently, the main drugs commonly used in clinical practice to treat insomnia include barbiturates, benzodiazepines and non-benzodiazepines.
The barbiturates have been gradually eliminated due to the side effects such as greater dependence and obvious withdrawal symptoms. Benzodiazepines and non-benzodiazepines are currently the mainstay of clinical prescribing by physicians, but the sedative-hypnotics in question are still only used for short-term sleep disorders, and long-term side effects are evident, including physical dependence, rebound insomnia, headaches, or other psychiatric disorders. Clinicians will also prescribe drugs that are not primary treatment aspects of the patient's condition, such as the antidepressant trazodone and the antihistamine benadryl, and long-term use of the above drugs can lead to cognitive impairment and some hangover effects. Based on the various limitations of clinical drugs, many patients choose to take melatonin or herbal health food as the main ingredient to overcome sleep disorders, but relevant studies have shown that melatonin has no effect on primary insomnia, and through clinical observation it was found that the duration of each sleep stage in patients taking melatonin is not significantly different from the placebo group, melatonin mainly plays the role of short-term induction, long-term use of melatonin on the human body also There are other potential hazards associated with long-term melatonin use.

Based on the above, there is a lack of medication or health food on the market that can be taken for a long time and can clearly improve the quality of sleep of patients.
The current situation is that there is no drug or health food on the market that can be taken for a long period of time and can clearly improve the quality of sleep.
 Gamma-aminobutyric acid (GABA) is an important neurotransmitter in the brain.
The main reason is that GABA cannot cross the blood-brain barrier and can only indirectly improve the sleep state of patients by indirectly affecting the central nervous system through the intestinal vagus nerve, the direct action of its own metabolite products or regulating the endocrine system.

5-Methyltetrahydrofolate is involved in the methionine cycle, through which it is further involved in the synthesis of a number of neurotransmitters, including 5-hydroxytryptamine.
Although folic acid has been used as a nutrient in all aspects of human life, especially in the prevention of neural tube abnormalities in newborns, no studies have been reported on the sleep improvement of folic acid or active folic acid, and the interaction with sedative-hypnotic drugs has not been suggested. The interaction with sedative-hypnotic drugs has not been proposed.

To be continued...