CN111643505B - Application of 5-MTHF (methyl tetrahydrofolate) in preparation of medicine for preventing and treating major depression - Google Patents
Application of 5-MTHF (methyl tetrahydrofolate) in preparation of medicine for preventing and treating major depression Download PDFInfo
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Abstract
The invention discloses an application of 5-MTHF (methyl tetrahydrofolate) in preparation of a medicine for preventing and treating major depression, belonging to the technical field of chemical pharmacy, and the technical scheme is characterized in that the medicine for preventing and treating major depression is produced by taking L-5-methyl tetrahydrofolate as a raw material, and a gingko active substance is also added, wherein the mass ratio of the L-5-methyl tetrahydrofolate to the gingko active substance is 10-20:1, and the invention provides a new medicine for preventing and treating major depression patients.
Description
Technical Field
The invention relates to the technical field of chemical pharmacy, in particular to application of 5-MTHF in preparing a medicine for preventing and treating major depression.
Background
The known compound L-5-methyltetrahydrofolate calcium is also called 5-MTHF, and the 5-MTHF in the following documents refers to L-5-methyltetrahydrofolate calcium. Molecular formula C20H23CaN7O6The molecular weight is 497.52, CAS number 151533-22-1, and the molecular structural formula is as follows:
calcium 5-methyltetrahydrofolate is a formylated derivative of folic acid reduction type, is an activated form of folic acid in vivo, has similar action to folic acid, and is mainly used as an antidote of folic acid antagonist. It is also used for megaloblastic anemia caused by pregnancy or infancy. L-5-methyltetrahydrofolic acid (L-5-MTHF) is a novel folic acid drug, which is commonly used as a food additive and a main component of a nutritional health product and is gradually known. L-5-MTHF is involved in many important biochemical reactions in vivo and has important pharmacological effects. The L-5-methyltetrahydrofolic acid calcium can penetrate through a blood brain barrier, has the characteristics of obvious curative effect and less side effect when being used for preventing and treating major depressive disorder, and gradually becomes a focus of common attention in the medical and pharmaceutical research fields.
Major depressive disorder is an emotional dysfunction caused by abnormalities in the genetic system (genes) or by a large change in the acquired environment in an individual patient. In China, it is reported that patients with coronary heart disease and depression are as high as 78.6%, old people are more prone to depression, and the prognosis of patients with depression is worse than that of patients without depression. Stroke can lead to depression. It has been investigated that depression occurs in 20% to 50% of patients in the first year after stroke. Especially, the disease damage is located in the left hemisphere, depression is more likely to occur in the frontal lobe, cardiovascular and cerebrovascular diseases are related to depression, the causal relationship may be bidirectional, the vascular diseases are easy to cause depression, and the depression further aggravates the process. A complex spiral causal chain is formed between depression and cardiovascular and cerebrovascular diseases. Therefore, attention is paid to the treatment of cardiovascular and cerebrovascular diseases while treating depression, and the psychopsychological disorder can be effectively controlled by the combined treatment of the two.
Disclosure of Invention
The invention aims to provide the application of 5-MTHF in preparing the medicine for preventing and treating the major depressive disorder, which can effectively treat cardiovascular and cerebrovascular diseases while controlling the psychopsychological abnormality of the depressive disorder, and the combined action of the two can provide a new medicine for preventing and treating the major depressive disorder.
The technical purpose of the invention is realized by the following technical scheme:
the application of 5-MTHF in preparing the medicine for preventing and treating the major depressive disorder is characterized in that the medicine for preventing and treating the major depressive disorder is produced by taking L-5-methyltetrahydrofolate calcium as a raw material, and a gingko active substance is also added, wherein the mass ratio of the L-5-methyltetrahydrofolate calcium to the gingko active substance is 10-20: 1.
Further, the ginkgo active substance is derived from ginkgo biloba leaves.
Further, the extraction method of the ginkgo active substance comprises the steps of taking ginkgo leaves, drying and cutting the ginkgo leaves into 10-20 meshes, adding 6-8 times of 60% ethanol, heating and refluxing at 60-70 ℃ for 2-3 times, extracting for 2-3 hours, combining the extracting solutions, carrying out suction filtration, collecting the filtrate, concentrating the filtrate to one third of the original volume, and standing for 24 hours; filtering to obtain clear filtrate, adsorbing with resin at flow rate of 15ml/min, sequentially washing with pure water, 15% ethanol and 30% ethanol, desorbing with 70% ethanol to obtain eluate, concentrating the eluate under reduced pressure, and drying to obtain semen Ginkgo active substance.
Furthermore, the health care medicine for preventing and treating major depressive disorder is produced by taking L-5-methyltetrahydrofolate calcium as a raw material.
Furthermore, the health care medicine comprises a fixed preparation and an oral liquid.
Furthermore, the L-5-methyl tetrahydrofolate calcium is used as a raw material to produce a therapeutic drug for preventing and treating major depression.
Further, the therapeutic drug includes an oral preparation and an injection.
Further, the oral preparation comprises tablets, capsules, granules and oral liquid.
Further, the injection includes large infusion solution and small volume injection solution.
In conclusion, the invention has the following beneficial effects:
1. the ginkgo active substance is added into the medicine for preventing and treating the major depression, which is produced by taking the L-5-methyltetrahydrofolate as the raw material, the ginkgo active substance contains flavonoid compounds and terpene lactone compounds, the two compounds can capture free radicals, inhibit platelet activating factors and promote the brain metabolism function of blood circulation meter, and the L-5-methyltetrahydrofolate can penetrate through the blood brain barrier and directly participate in the biochemical process of an organism, so that the biological activity is higher; the two drugs act simultaneously, can effectively treat the cardiovascular and cerebrovascular diseases while controlling the psychopsychological abnormality of the depression, and provides a new medicine for preventing and treating the major depression.
2. The health care medicine for treating major depressive disorder is produced by taking the L-5-methyltetrahydrocalcium folate as a raw material, and the health care medicine is utilized to realize the prevention of the depressive disorder and reduce the incidence rate of the depressive disorder.
Detailed Description
Example 1:
the medicine for preventing and treating the major depression is produced by taking L-5-methyltetrahydrofolate calcium as a raw material, and a gingko active substance is also added, wherein the mass ratio of the L-5-methyltetrahydrofolate calcium to the gingko active substance is 20: 1.
The synthesis process of the L-5-methyl tetrahydrocalcium folate comprises the following steps: folic acid is used as a raw material, sodium borohydride is used as a reducing agent, sodium hydrosulfite is added into a reaction solution to be used as an antioxidant, and the pH value of the reaction solution is adjusted to 4.5 to prepare the L-5-methyl tetrahydrocalcium folate.
The extraction method of the ginkgo active substance comprises the steps of taking ginkgo leaves, drying and cutting the ginkgo leaves into 10-20 meshes, adding 8 times of 60% ethanol, heating to 70 ℃, carrying out reflux extraction for 3 times for 3 hours, combining extracting solutions, carrying out suction filtration, collecting filtrate, concentrating the filtrate to one third of the original volume, and standing for 24 hours; performing suction filtration to obtain clear filtrate, adsorbing with resin, loading onto column, washing folium Ginkgo and resin at a ratio of 1:2 and a flow rate of 15ml/min with pure water, 15% ethanol and 30% ethanol respectively, desorbing with 70% ethanol to obtain eluate, concentrating the eluate under reduced pressure, and drying to obtain semen Ginkgo active substance.
The treatment medicine for preventing and treating the major depressive disorder is produced by taking L-5-methyltetrahydrocalcium folate as a raw material, the treatment medicine is oral liquid in an oral preparation, and the specification of the oral liquid is 20 mg.
The usage and dosage are as follows: 2 times daily, 20mg each time; after two weeks, the dose was adjusted to 60mg once daily.
Example 2:
the medicine for preventing and treating major depression is produced by taking L-5-methyltetrahydrofolate calcium as a raw material, and a gingko active substance is also added, wherein the mass ratio of the L-5-methyltetrahydrofolate calcium to the gingko active substance is 18: 1.
The synthesis process of the L-5-methyl tetrahydrocalcium folate comprises the following steps: folic acid is used as a raw material, sodium borohydride is used as a reducing agent, sodium hydrosulfite is added into a reaction solution to be used as an antioxidant, and the pH value of the reaction solution is adjusted to 4.5 to prepare the L-5-methyl tetrahydrocalcium folate.
The extraction method of the ginkgo active substance comprises the steps of taking ginkgo leaves, drying and cutting the ginkgo leaves into 10-20 meshes, adding 60% ethanol in an amount which is 6 times that of the ginkgo leaves, heating to 65 ℃, carrying out reflux extraction for 3 times for 2 hours, combining extracting solutions, carrying out suction filtration, collecting filtrate, concentrating the filtrate to one third of the original volume, and standing for 24 hours; performing suction filtration to obtain clear filtrate, adsorbing with resin, loading onto column, washing folium Ginkgo and resin at a ratio of 1:2 and a flow rate of 15ml/min with pure water, 15% ethanol and 30% ethanol respectively, desorbing with 70% ethanol to obtain eluate, concentrating the eluate under reduced pressure, and drying to obtain semen Ginkgo active substance.
The therapeutic medicine for preventing and treating the major depressive disorder is produced by taking L-5-methyltetrahydrocalcium folate as a raw material, the therapeutic medicine is a capsule in an oral preparation, and the specification of the capsule is 10 mg.
The usage and dosage are as follows: 3 times daily, 10mg each time; after two weeks, the dose was adjusted to 20mg 2 times daily.
Example 3:
the medicine for preventing and treating the major depression is produced by taking L-5-methyltetrahydrofolate calcium as a raw material, and a ginkgo active substance is also added, wherein the mass ratio of the L-5-methyltetrahydrofolate calcium to the ginkgo active substance is 15: 1.
The synthesis process of the L-5-methyl tetrahydrocalcium folate comprises the following steps: folic acid is used as a raw material, sodium borohydride is used as a reducing agent, sodium hydrosulfite is added into a reaction solution to be used as an antioxidant, and the pH value of the reaction solution is adjusted to 4.5 to prepare the L-5-methyl tetrahydrocalcium folate.
The extraction method of the ginkgo active substance comprises the steps of taking ginkgo leaves, drying and cutting the ginkgo leaves into 10-20 meshes, adding 8 times of 60% ethanol, heating to 60 ℃, carrying out reflux extraction for 2 times for 3 hours, combining extracting solutions, carrying out suction filtration, collecting filtrate, concentrating the filtrate to one third of the original volume, and standing for 24 hours; performing suction filtration to obtain clear filtrate, adsorbing with resin, loading onto column, washing folium Ginkgo and resin at a ratio of 1:2 and a flow rate of 20ml/min with pure water, 15% ethanol and 30% ethanol respectively, desorbing with 70% ethanol to obtain eluate, concentrating the eluate under reduced pressure, and drying to obtain semen Ginkgo active substance.
The treatment medicine for preventing and treating the major depressive disorder is produced by taking L-5-methyltetrahydrofolic acid calcium as a raw material, the treatment medicine is granules in an oral preparation, and the specification of the granules is 15 mg.
The usage and dosage are as follows: is administered with 90 deg.C above boiled water 2 times a day, 15mg each time; after two weeks, the dose was adjusted to 30mg once daily 1 time.
Example 4:
example 4 as comparative example 1, a drug for the prevention and treatment of major depressive disorder, produced using calcium L-5-methyltetrahydrofolate as a raw material, was further added with a ginkgo active substance, the mass ratio of calcium L-5-methyltetrahydrofolate to ginkgo active substance being 20: 1.
The synthesis process of the L-5-methyl tetrahydrocalcium folate comprises the following steps: folic acid is used as a raw material, sodium borohydride is used as a reducing agent, sodium hydrosulfite is added into a reaction solution to be used as an antioxidant, and the pH value of the reaction solution is adjusted to 4.5 to prepare the L-5-methyl tetrahydrocalcium folate.
The extraction method of the ginkgo active substance comprises the steps of taking ginkgo leaves, drying and cutting the ginkgo leaves into 10-20 meshes, adding 8 times of 60% ethanol, heating to 60 ℃, carrying out reflux extraction for 2 times for 3 hours, combining extracting solutions, carrying out suction filtration, collecting filtrate, concentrating the filtrate to one third of the original volume, and standing for 24 hours; and filtering to obtain clear filtrate. The subsequent purification and concentration steps are eliminated. Directly concentrating the filtrate under reduced pressure to obtain semen Ginkgo active substance.
The therapeutic medicine for preventing and treating the major depressive disorder is produced by taking L-5-methyltetrahydrocalcium folate as a raw material, the therapeutic medicine is a capsule in an oral preparation, and the specification of the capsule is 10 mg.
The usage and dosage are as follows: 3 times daily, 10mg each time; after two weeks, the dose was adjusted to 20mg 2 times daily.
Example 5:
example 5 as comparative example 2, a drug for the prevention and treatment of major depressive disorder, produced using calcium L-5-methyltetrahydrofolate as a raw material, was further added with a ginkgo active substance, the mass ratio of calcium L-5-methyltetrahydrofolate to ginkgo active substance being 18: 1.
The extraction method of the ginkgo active substance comprises the steps of taking ginkgo leaves, drying and cutting the ginkgo leaves into 10-20 meshes, adding 8 times of 60% ethanol, heating to 70 ℃, carrying out reflux extraction for 3 times for 3 hours, combining extracting solutions, carrying out suction filtration, collecting filtrate, concentrating the filtrate to one third of the original volume, and standing for 24 hours; filtering to obtain clear filtrate; the subsequent purification and concentration steps are eliminated. Directly concentrating the filtrate under reduced pressure to obtain semen Ginkgo active substance.
The therapeutic medicine for preventing and treating the major depressive disorder is produced by taking L-5-methyltetrahydrocalcium folate as a raw material, the therapeutic medicine is a capsule in an oral preparation, and the specification of the capsule is 10 mg.
The usage and dosage are as follows: 3 times daily, 10mg each time; after two weeks, the dose was adjusted to 20mg 2 times daily.
The specific implementation process comprises the following steps:
the oral liquid and granules prepared in the examples 1-3 and the comparative examples 1-2 are used for clinically treating the aged patients with depression, 50 patients are randomly selected, the age of the patients is more than or equal to 60 years, and the average course of disease is 7.6 months. The patients were divided into 5 groups by a random number method, and the reactions of the patients after 1, 3, 5 weeks were observed corresponding to the administration of the prepared drugs in examples 1 to 3 and comparative examples 1 to 2, respectively.
As shown in table 1, the observation indices: the patient's depressed state was assessed by the hamilton depression scale (HAMD) for 1, 3, 5 weeks of treatment, scoring criteria: if the total score is lower than 7, the result is normal; a total score of 7-17 indicates possible depression; the total score is 17-24 points, which indicates depression, and the total score exceeds 24 points, which indicates severe depression. Calculating the average score of each group of patients, and judging the reaction of the patients after taking the medicine.
TABLE 1 HAMD scores in five groups of patients
| Group of | Before treatment | After 1 week | After 3 weeks | After 5 weeks |
| Example 1 | 25.21±3.01 | 21.56±3.12 | 12.56±3.25 | 8.17±3.54 |
| Example 2 | 25.32±4.21 | 22.32±3.02 | 15.45±3.20 | 10.28±3.12 |
| Example 3 | 25.41±3.23 | 23.36±3.05 | 13.35±3.04 | 9.18±3.25 |
| Comparative example 1 | 25.23±4.25 | 24.18±4.15 | 18.67±3.06 | 16.11±3.56 |
| Comparative example 2 | 25.12±4.53 | 23.89±4.52 | 17.46±3.08 | 15.17±3.14 |
As can be seen from the data in Table 1, the HAMD score of the patients after taking the therapeutic drug prepared by the present invention is on the decreasing trend, and the patients after taking the drug for 5 weeks are best represented by the HAMD score of about 8.17, which is close to the standard of normal people, and the comparison results of examples 1-3 and comparative examples 1-2 show that the purification step of extracting the ginkgo active substance according to the present invention can improve the action effect of the drug prepared by the present invention. In conclusion, the treatment medicine prepared by the invention can effectively relieve depression symptoms of patients.
The present embodiment is only for explaining the present invention, and it is not limited to the present invention, and those skilled in the art can make modifications of the present embodiment without inventive contribution as needed after reading the present specification, but all of them are protected by patent law within the scope of the claims of the present invention.
Claims (5)
- The application of L-5-methyl tetrahydrofolate calcium in preparing a medicine for preventing and treating major depression is characterized in that the medicine for preventing and treating major depression is produced by taking L-5-methyl tetrahydrofolate calcium as a raw material, and a gingko active substance is added, wherein the mass ratio of the L-5-methyl tetrahydrofolate calcium to the gingko active substance is 10-20: 1;the extraction method of the ginkgo active substance comprises the steps of taking ginkgo leaves, drying and cutting the ginkgo leaves into 10-20 meshes, adding 6-8 times of 60% ethanol, heating and refluxing at 60-70 ℃ for 2-3 times, extracting for 2-3 hours, combining extracting solutions, collecting filtrate after suction filtration, concentrating the filtrate to one third of the original volume, and standing for 24 hours; filtering to obtain clear filtrate, adsorbing with resin at flow rate of 15ml/min, sequentially washing with pure water, 15% ethanol and 30% ethanol, desorbing with 70% ethanol to obtain eluate, concentrating the eluate under reduced pressure, and drying to obtain semen Ginkgo active substance.
- 2. Use of calcium L-5-methyltetrahydrofolate according to claim 1 for the preparation of a medicament for the prevention and treatment of major depressive disorders, characterized in that: the L-5-methyl tetrahydrofolic acid calcium is used as a raw material to produce a therapeutic medicine for preventing and treating major depression.
- 3. Use of calcium L-5-methyltetrahydrofolate according to claim 2 for the preparation of a medicament for the prevention and treatment of major depressive disorders, characterized in that: the therapeutic drug comprises an oral preparation and an injection.
- 4. Use of calcium L-5-methyltetrahydrofolate according to claim 3, for the preparation of a medicament for the prevention and treatment of major depressive disorders, characterized in that: the oral preparation comprises tablets, capsules, granules and oral liquid.
- 5. Use of calcium L-5-methyltetrahydrofolate according to claim 3, for the preparation of a medicament for the prevention and treatment of major depressive disorders, characterized in that: the injection comprises large infusion solution and small-volume injection solution.
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