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CN117257821A - Composition containing disodium uridylate and application thereof - Google Patents

Composition containing disodium uridylate and application thereof Download PDF

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Publication number
CN117257821A
CN117257821A CN202210673700.1A CN202210673700A CN117257821A CN 117257821 A CN117257821 A CN 117257821A CN 202210673700 A CN202210673700 A CN 202210673700A CN 117257821 A CN117257821 A CN 117257821A
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food
vivo
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pharmaceutical composition
dose
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杜心赟
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    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • A61K31/7072—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
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    • A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
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    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
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    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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    • A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
    • A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
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Abstract

A composition comprising disodium uridylate and use thereof is provided which is effective in increasing in vivo, particularly brain uridine levels, and/or in decreasing in vivo homocysteine levels.

Description

Composition containing disodium uridylate and application thereof
Technical Field
The present invention relates to a composition containing disodium uridylate and uses thereof.
Background
Uridine is the major pyrimidine nucleoside form absorbed by the brain for synthesis of nucleic acids and cell membranes (curr. Top. Med. Chem.2011,11,1058). Uridine is also a biologically active molecule in the brain, and plays an important role in the central nervous system such as memory and neuroplasticity.
Animal experiments prove that (Cell Discovery 2022,8:6, 1-22), the uridine content in the blood plasma, the muscle and the brain of the mice is increased by injecting or perfusing the mice with gastric uridine, and simultaneously, promotion of repair after injury of 5 tissues and organs, including regeneration of injury such as muscle, cardiovascular and cerebrovascular diseases, hair, liver fibrosis and the like, is observed. For example, muscle-damaged mice have enhanced limb grip, hair-damaged mice have achieved hair regeneration, cardiac contractility of myocardial mice has been enhanced, and liver fibrosis of mice has been alleviated. The old mice are directly fed with uridine for two months, and the systemic movement capacity of the mice is also obviously improved. Experiments have also found that cells or tissues containing higher levels of uridine are more regenerative. It is well known that uridine can also enhance the plasticity of the brain nerve, i.e. enhance the adaptation, memory and learning ability of the brain, by creating and reorganizing synaptic connections. Whereas aging disorders generally reduce the number of synapses or neuronal cell connections for neurotransmitters to transmit information to the brain and body. Thus, increasing in vivo tissue, especially increasing uridine levels in the brain, helps to delay the progression of aging. Uridine is a synthetic precursor of phospholipids and cell membranes, and supplementing uridine levels in the brain can increase brain cytidine sodium choline (CDP-choline) levels, and promote recovery from brain trauma or postoperative conscious disturbance. Increasing brain neuron synapse formation (Nutrition Reviews, 2010,68, suppl.2, S88-S-101) has effects of improving memory function, optimizing mitochondrial function, improving emotion, protecting nerves, etc.
Low uridine levels are also one of the important features of Alzheimer's and Alzheimer's patients (Alzheimer's' device.2020, 12, e 12120). Supplementing uridine levels in the brain is beneficial in preventing or ameliorating senile dementia and Alzheimer's disease.
Homocysteine levels are also highly associated with cardiovascular and cerebrovascular diseases, senile dementia, alzheimer's disease, cognitive dysfunction and are high risk factors for these diseases (am. J. Clin. Nutr.2005, 82, 636). Therefore, supplementation with uridine, phospholipids and DHA can reduce homocysteine levels, and is very important for improving or preventing blood cerebrovascular diseases, senile dementia, cognitive dysfunction, alzheimer's disease and the like.
Coenzyme I participates in almost all metabolism of cells, provides energy for the cells, repairs damaged DNA, and is necessary for human body. However, it decreases with age. Thus, increasing coenzyme I levels in vivo is beneficial to physical health (PloS One,2012,7, e 42357). The increase in coenzyme I levels achieves effects of preventing nerve damage and improving cognitive and physiological functions in animals in a mouse model of Alzheimer (PNAS 2018, E1876).
Although direct intragastric uridine administration in mice can increase uridine levels in vivo, its bioavailability is only 7% (Cancer chemther. Pharmacol.1986,17,236). The effect of oral uridine on uridine levels in the brain is not reported in the literature. Accordingly, there is a need for research and development of effective products and methods for supplementing uridine levels, particularly in the brain, reducing homocysteine levels, and/or increasing coenzyme I levels in the body.
Disclosure of Invention
The invention aims to develop a novel composition which can effectively improve the in vivo uridine level, especially the uridine level of brain, and/or can effectively reduce the in vivo homocysteine level, preferably can effectively improve the in vivo uridine level (especially the same uridine level of brain) and simultaneously can effectively reduce the in vivo homocysteine level, thereby achieving the purposes of improving or preventing diseases such as blood cerebral vascular diseases, senile dementia, cognitive dysfunction, alzheimer and the like. Preferably, coenzyme I levels in the body are also effectively increased.
The inventors have unexpectedly found that mouse lavage of disodium uridylate is more effective in increasing brain uridine levels than uridine. In addition, it has been found that homocysteine levels in vivo are effectively reduced. Further combined with the bladderBase and/or acetylcholine and/or phosphorylcholine (a-GPC) and/or glycerophosphatidylcholine and/or modified soybean phospholipids, and/or further combined with nervonic acid and/or DHA and/or docosahexaenoic acid lipid, and/or further combined with vitamin B 6 In combination with, and/or further with vitamin B 12 The combination of the above drugs and/or folic acid can effectively increase the level of uridine in vivo and reduce the level of homocysteine in vivo. Further, by combined administration of nicotinamide and/or nicotinamide riboside and/or nicotinamide mononucleic acid and/or nicotinic acid to the mice, the brain uridine level of the mice can be improved, the homocysteine level in the bodies can be effectively reduced, and the coenzyme I level in the bodies, particularly in the livers, of the mice can be improved.
In view of this, the present invention provides a food or pharmaceutical composition characterized by comprising disodium uridylate and optionally food additives or pharmaceutical excipients. The food additive or pharmaceutical adjuvant comprises other vitamins or minerals.
Preferably, the food composition or pharmaceutical composition further comprises a compound selected from choline, acetylcholine, phosphorylcholine (a-GPC), glycerophosphorylcholine, modified soybean phospholipid, nervonic acid, DHA, docosahexaenoic acid lipid, and vitamin B 6 Vitamin B 12 One or more of folic acid.
Preferably, the food composition or pharmaceutical composition further contains one or more selected from choline, acetylcholine, phosphorylcholine (a-GPC), glycerophosphorylcholine, modified soybean phospholipids.
Preferably, the food composition or pharmaceutical composition further contains one or more selected from choline, acetylcholine, phosphorylcholine (a-GPC), glycerophosphorylcholine, modified soybean phospholipids; nervonic acid and/or DHA and/or docosahexaenoic acid lipid.
Preferably, the food composition or pharmaceutical composition further contains one or more selected from choline, acetylcholine, phosphorylcholine (a-GPC), glycerophosphorylcholine, modified soybean phospholipids; nervonic acid and/or DHA and/or docosahexaenoic acid lipid; vitamin B 6 。
Preferably, the food composition or pharmaceutical composition further contains one or more selected from choline, acetylcholine, phosphorylcholine (a-GPC), glycerophosphorylcholine, modified soybean phospholipids; nervonic acid and/or DHA and/or docosahexaenoic acid lipid; vitamin B 6 The method comprises the steps of carrying out a first treatment on the surface of the Vitamin B 12 。
Preferably, the food composition or pharmaceutical composition further contains one or more selected from choline, acetylcholine, phosphorylcholine (a-GPC), glycerophosphorylcholine, modified soybean phospholipids; nervonic acid and/or DHA and/or docosahexaenoic acid lipid; vitamin B 6 The method comprises the steps of carrying out a first treatment on the surface of the Vitamin B 12 The method comprises the steps of carrying out a first treatment on the surface of the Folic acid.
Preferably, the food composition or the pharmaceutical composition further comprises one or more selected from nicotinamide, nicotinamide riboside, nicotinamide mononucleic acid, and nicotinic acid.
Preferably, the food composition or pharmaceutical composition is for increasing uridine levels in vivo, in particular in the brain.
Preferably, the food composition or pharmaceutical composition is for reducing homocysteine levels in vivo.
Preferably, the food composition or pharmaceutical composition is for increasing in vivo, in particular brain uridine levels, while reducing in vivo homocysteine levels.
Preferably, the food or pharmaceutical composition is used to increase in vivo, in particular brain uridine levels, while decreasing homocysteine levels in vivo and increasing coenzyme I levels in vivo, in particular in the liver.
In another aspect, the present invention also provides the use of the above-described food composition as a food for increasing in vivo, in particular brain uridine levels; the invention also provides the use of the above food composition as a food for reducing homocysteine levels in vivo; preferably, the use of the above-described food composition as a food for increasing in vivo, in particular brain uridine levels, while decreasing in vivo homocysteine levels is provided, preferably the use of the above-described food composition as a food for increasing in vivo, in particular brain uridine levels, decreasing in vivo homocysteine levels, while increasing in vivo, in particular in the liver coenzyme I levels is provided.
The invention also provides the use of the above food composition for the preparation of a food for increasing in vivo, in particular brain uridine levels; the invention also provides application of the food composition in preparing foods for reducing homocysteine level in vivo; preferably, there is provided the use of the above-described food composition for the preparation of a food product for increasing in vivo, in particular brain uridine levels, while decreasing in vivo homocysteine levels; preferably, there is provided the use of the above-described food composition for the preparation of a food product for increasing in vivo, in particular brain uridine levels, decreasing in vivo homocysteine levels, and simultaneously increasing in vivo, in particular in the liver, coenzyme I levels.
Preferably, the food comprises nutritional food, health food.
The invention also provides application of the pharmaceutical composition in preparing medicines for improving the uridine levels in vivo, especially in brain; the invention also provides application of the pharmaceutical composition in preparing medicines for reducing homocysteine level in vivo; preferably, there is provided the use of the above pharmaceutical composition for the manufacture of a medicament for increasing in vivo, in particular brain uridine levels, while decreasing in vivo homocysteine levels; preferably, there is provided the use of the above pharmaceutical composition for the manufacture of a medicament for increasing in vivo, in particular brain uridine levels, decreasing in vivo homocysteine levels, and simultaneously increasing in vivo, in particular in the liver, coenzyme I levels.
In another aspect, the invention also provides a method of increasing uridine levels in vivo, particularly in the brain; in addition, the present invention provides a method of reducing homocysteine levels in the body, preferably, increasing levels of uridine in the body, particularly brain, while reducing levels of homocysteine in the body, preferably, increasing levels of uridine in the body, particularly brain, reducing levels of homocysteine in the body, while increasing levels of coenzyme I in the body, particularly liver, comprising administering to an individual in need thereof an effective amount of a food composition or pharmaceutical composition as described above.
Preferably, the dose of disodium uridylate is preferably 100mg to 3000 mg, more preferably 300mg to 1000 mg, still more preferably 500mg to 700 mg per day.
The total dose of one or more of choline, acetylcholine, phosphorylcholine (a-GPC), glycerophosphorylcholine, and modified soybean phospholipid is preferably 100mg to 3000 mg, more preferably 100mg to 1000 mg, still more preferably 200 mg to 600 mg per day.
The total dose of nervonic acid and/or DHA and/or docosahexaenoic acid lipid is preferably 100mg to 3000 mg, more preferably 100mg to 1000 mg, still more preferably 100mg to 500mg per day.
Vitamin B 6 The dosage of (2) is preferably 100mg to 3000 mg, more preferably 100mg to 1000 mg, still more preferably 100mg to 300mg per day.
The dose of vitamin B12 is preferably 1. Mu.g to 10 mg, more preferably 1. Mu.g to 3 mg, still more preferably 1. Mu.g to 1mg per day.
The dosage of folic acid is preferably 0.1 mg to 100mg, more preferably 0.1 mg to 10 mg, still more preferably 0.1 mg to 0.5 mg per day.
The total dose of nicotinamide and/or nicotinamide riboside and/or nicotinamide mononucleotide and/or niacin is preferably 20 mg to 3000 mg, more preferably 50mg to 1000 mg, even more preferably 100mg to 600 mg per day.
In the present invention, the dosage form of the food composition or the pharmaceutical composition is not limited, and includes, but is not limited to, oral solid preparations or oral liquid preparations. Preferably, the dosage form of the food or pharmaceutical composition includes, but is not limited to, solid beverages, tablets (e.g., tabletted candies, lozenges), granular formulations, powder formulations, lyophilized formulations.
Preferably, the food composition or pharmaceutical composition unit preparation contains 100 mg-3000 mg disodium uridylate.
Animal experiments have shown that administration of disodium uridylate can be effective in increasing levels of uridine in vivo, particularly in the brain, and/or in reducing levels of homocysteine in vivo, or in increasing levels of uridine in vivo, particularly in the brain, while reducing levels of homocysteine. It is therefore contemplated that any of the compositions of the present invention containing disodium uridylate may be administered to effectively increase uridine levels in humans, particularly the brain, and/or to effectively decrease homocysteine levels in the body.
Animal experiments have shown that the combination of disodium uridylate and nicotinamide or nicotinamide riboside or nicotinamide mononucleic acid or nicotinic acid can not only improve the brain uridine level of animals and/or reduce the homocysteine level in vivo, but also improve the coenzyme I level in vivo. It is therefore contemplated that any composition of the invention comprising disodium uridylate and nicotinamide and/or nicotinamide riboside and/or nicotinamide mononucleic acid and/or niacin can increase uridine levels and/or decrease homocysteine levels in the body, particularly the brain, as well as increase coenzyme I levels in the body.
Detailed Description
Animal test
Example 1 determination of brain uridine content in mice were given disodium oxyuridylate and uridine, respectively
The test method is as follows:
formulation and dosing: the appropriate amount of the test sample is precisely weighed and mixed with an appropriate volume of physiological saline to obtain a clear solution or a uniform suspension. Animals were dosed within 4 hours after preparation. The formulations will be administered by oral gavage following standard protocols (SOP). The dose was determined by the body weight of animals collected on the morning of the day of administration.
Brain tissue treatment: brain tissue was collected at each time point, washed twice with pre-chilled deionized water, and the filter paper was blotted dry. Brain tissue was immediately homogenized with 10 volumes of methanol-water (1:2, v/v) and appropriate amount of brain tissue homogenate (e.g., 200uL homogenate) was immediately taken after homogenization, after precipitation of the sample on wet ice, the supernatant was centrifuged and stored in a refrigerator at-70.+ -. 10 ℃ until LC-MS/MS analysis was performed.
Each group of mice was perfused with physiological saline, disodium uridylate (1.0 mmol/kg), and uridine (1 mmol/kg), respectively, 3 mice per group. Brain tissue samples were taken at time points of 0.25, 0.5, 1, 2, 4, 8, 12, 15, 19, 24h, respectively, and the concentrations of uridine in brain tissues were measured by LC-MS/MS test as described above, and the results (average values) are shown in table 1.
TABLE 1 content of uridine in brain after lavage of disodium uridylate and uridine, respectively
The disodium uridylate of the lavage mice increases the brain uridine level by 13.8%, which is significantly higher than that of the direct lavage mice by 4.7%.
EXAMPLE 2 lavage of mice disodium uridylate and nicotinamide or nicotinamide riboside, brain uridine levels and liver coenzyme I levels were determined
The test method for the level of brain uridine was the same as in example 1.
The liver coenzyme I level test method is as follows:
formulation and dosing: the appropriate amount of the test sample is precisely weighed and mixed with an appropriate volume of physiological saline to obtain a clear solution or a uniform suspension. Animals were dosed within 4 hours after preparation. The formulations will be administered by oral gavage following standard protocols. The dose was determined by the body weight of animals collected on the morning of the day of administration.
Liver treatment: liver tissue was collected at each time point, washed twice with pre-chilled deionized water, and the filter paper was blotted dry. Liver tissue was homogenized immediately with 10 volumes of methanol-water solution (1:2, v/v), and appropriate amount of liver tissue homogenate (e.g., 200uL homogenate) was taken immediately after homogenization, after precipitation of the sample on wet ice, the supernatant was centrifuged and stored in a refrigerator at-70±10 ℃ until LC-MS/MS analysis was performed.
Each group of mice was perfused with disodium uridylate (1.0 mmol/kg) and nicotinamide (Nam, 0.64mmol,78 mg/kg), disodium uridylate (1.0 mmol/kg) and nicotinamide riboside (NR, 0.64mmol,185 mg/kg), disodium uridylate (1 mmol/kg) and nicotinamide mononucleotide (0.64 mmol,214 mg), or disodium uridylate (1.0 mmol/kg) and nicotinic acid (NA, 0.64mmol,78 mg), respectively, 3 mice per group. Liver samples were obtained at time points of 0.25, 0.5, 1, 2, 4, 8, 12, 15, 19, 24h, respectively, and the concentrations (average) of coenzyme I (NAD+) in the liver were determined by the LC-MS/MS test as described above, and the results are shown in Table 2.
TABLE 2 brain uridine and liver NAD content after separate intragastric disodium uridylate compositions
Nad=coenzyme I.
The results in Table 2 show that the increased levels of coenzyme I in the liver of mice lavaged with disodium uridylate and nicotinamide are comparable to, but significantly higher than, that produced by equimolar amounts of disodium uridylate and nicotinamide riboside, or disodium uridylate and nicotinamide mononucleic acid. Nicotinamide is significantly less costly than nicotinamide riboside and nicotinamide mononucleotide.
Example 3 preliminary clinical trial
Test of plasma uridine and homocysteine in plasma concentrations
The test substance or composition dosage selected for the test is encapsulated and selected for oral administration to healthy volunteers. The weight is about 60 kg.
The substances or compositions administered for the test are respectively as follows:
test 3.1: orally taken capsule containing 500mg of disodium uridylate
Test 3.2: oral disodium uridylate capsule (dose 500 mg) and glycerophosphatidylcholine (alfa GPC) capsule (dose 200 mg)
Test 3.3: oral disodium uridylate capsule (dose 500 mg), glycerophosphatidylcholine (alfa GPC) capsule (dose 200 mg) and docosahexaenoic acid (DHA) capsule (dose 100 mg)
Test 3.4: oral disodium uridylate capsule (dose 500 mg), glycerophosphatidylcholine (alfa GPC) capsule (dose 200 mg), docosahexaenoic acid (DHA) capsule (dose 100 mg) and vitamin B 6 Capsule (dosage 50 mg)
Test 3.5: oral disodium uridylate capsule500mg dose), glycerophosphatidylcholine (alfa GPC) capsule (200 mg dose), docosahexaenoic acid (DHA) capsule (100 mg dose), vitamin B 6 Capsule (dose 50 mg) and vitamin B 12 Capsule (dosage 1 mg)
Test 3.6: oral disodium uridylate capsule (dose 500 mg), glycerophosphatidylcholine (alfa GPC) capsule (dose 200 mg), docosahexaenoic acid (DHA) capsule (dose 100 mg), vitamin B 6 Capsule (dosage 50 mg), vitamin B 12 Capsules (dose 1 mg) and folic acid capsules (dose 0.4 mg)
Test 3.7: oral disodium uridylate capsule (dose 500 mg) and nicotinamide capsule (dose 366 mg)
Test 3.8: oral disodium uridylate capsule (dose 500 mg), nicotinamide capsule (dose 366 mg) and glycerophosphatidylcholine (alfa GPC) capsule (dose 200 mg)
Test 3.9: oral disodium uridylate capsule (dose 500 mg), nicotinamide capsule (dose 366 mg), glycerophosphatidylcholine (alfa GPC) capsule (dose 200 mg) and docosahexaenoic acid (DHA) capsule (dose 100 mg)
Test 3.10: oral disodium uridylate capsule (dose 500 mg), nicotinamide capsule (dose 366 mg), glycerophosphatidylcholine (alfa GPC) capsule (dose 200 mg), docosahexaenoic acid (DHA) capsule (dose 100 mg) and vitamin B 6 Capsule (dosage 50 mg)
Test 3.11: oral disodium uridylate capsule (dose 500 mg), nicotinamide capsule (dose 366 mg), glycerophosphatidylcholine (alfa GPC) capsule (dose 200 mg), docosahexaenoic acid (DHA) capsule (dose 100 mg), vitamin B 6 Capsule (dose 50 mg) and vitamin B 12 Capsule (dosage 1 mg)
Test 3.12: oral disodium uridylate capsule (dose 500 mg), nicotinamide capsule (dose 366 mg), glycerophosphatidylcholine (alfa GPC) capsule (dose 200 mg), docosahexaenoic acid (DHA) capsule (dose 100 mg), vitamin B 6 Capsule (dosage 50 mg), vitamin B 12 Capsules (dose 1 mg) and folic acid capsules (dose 0.4mg)
The test method is as follows:
1. the capsules were taken daily breakfast to healthy adult volunteers (weighing about 60 kg).
2. Blood collection: blood (5 mL) was drawn from the tester at the time of the test. All blood samples were transferred to pre-chilled commercial EDTA-K2 tubes and placed on wet ice until centrifugation.
3. Plasma treatment: the blood sample was centrifuged (3200 rpm, 10 min) at about 4 ℃. Plasma was collected separately and transferred to pre-labeled PP tubes in wet ice at each time point and then immediately precipitated using ACN (6 IS) (plasma: ACN ratio 1:4). Again centrifuged (10 min, 12000 rpm) and the supernatant obtained. Quick-freeze on dry ice and hold at-70±10 ℃ until LC/MS analysis was performed. The plasma concentrations of uridine and homocysteine were measured separately.
Run 3.1
After 12 weeks of taking disodium uridylate capsules (dose 500 mg/day) after each evening meal in two healthy male volunteers (60 years), the plasma uridine and homocysteine levels were measured on the pre-day (baseline) and on the last morning on an empty stomach, and the results are shown in table 3 (the values are the average of two persons).
TABLE 3 uridine and homocysteine content (. Mu.mol/mL)
Base line Last day Increment of Increment%
Uridine (uridine) 4.05 6.50 2.45 +61
Homocysteine 11.25 10.35 0.9 -8.0
Run 3.2
Plasma homocysteine levels were measured in two healthy male volunteers (60 years) 12 weeks after daily administration of disodium uridylate capsule (dose 500 mg/day) and alfa-GPD capsule (dose 300 mg/day) after supper, the day before administration (baseline) and the day after the last morning on an empty stomach, and the results are shown in Table 4 (values are average of two persons).
TABLE 4 homocysteine content (. Mu. Mol/mL)
Base line Last day Variation of Increment (%)
Homocysteine 11.21 9.93 1.28 -11.4
Run 3.3
Plasma homocysteine levels were measured in two healthy male volunteers (60 years) after 12 weeks of daily use of disodium uridylate capsule (dose 500 mg/day), alfa-GPD capsule (dose 300 mg/day) and DHA capsule (dose 100 mg/day) after dinner, on the day before administration (baseline) and on the last morning on an empty stomach, and the results are shown in Table 5 (values are average of two persons).
TABLE 5 homocysteine content (. Mu.mol/mL)
Base line Last day Variation of Increment (%)
Homocysteine 11.40 10.05 1.35 -11.8
Run 3.4
Two healthy male volunteers (60 years old) took disodium uridylate capsule (dose 500 mg/day), alfa-GPD capsule (dose 300 mg/day), DHA capsule (dose 100 mg/day) and B after dinner every day 6 The homocysteine content in plasma was measured 12 weeks after the capsule (dose 50 mg/day), the day before administration (baseline) and the last day in the morning on an empty stomach, and the results are shown in table 6 (the values are the average of two persons).
TABLE 6 homocysteine content (. Mu.mol/mL)
Base line Last day Variation of Increment (%)
Homocysteine 12.15 10.31 1.84 -15.1
Run 3.5
Two healthy male volunteers (60 years old) eachAfter supper, the medicine is taken in form of disodium uridylate capsule (500 mg/day dose), alfa-GPD capsule (300 mg/day dose), DHA capsule (100 mg/day dose), B 6 Capsules (dose 50 mg/day) and B 12 After 12 weeks of the capsule (dose 1 mg/day), the homocysteine content in plasma was measured on the day before (baseline) and on the morning on an empty stomach, and the results are shown in Table 7 (the values are the average of two persons).
TABLE 7 homocysteine content (. Mu.mol/mL)
Base line Last day Variation of Increment (%)
Homocysteine 13.25 11.19 2.06 -15.6
Run 3.6
Two healthy male volunteers (60 years old) took disodium uridylate capsule (dose 500 mg/day), alfa-GPD capsule (dose 300 mg/day), DHA capsule (dose 100 mg/day), B after dinner every day 6 Capsule (dosage 50 mg/day), B 12 After 12 weeks of capsules (dose 1 mg/day) and folic acid capsules (dose 0.4 mg/day), blood was measured on the day before (baseline) and on the morning on an empty stomachHomocysteine content in the pulp is shown in Table 8 (the values are average values of two persons).
TABLE 8 homocysteine content (. Mu.mol/mL)
Base line Last day Variation of Increment (%)
Homocysteine 11.89 9.81 2.08 -17.5
Run 3.7
After 12 weeks of taking disodium uridine capsules (dose 500 mg/day) and nicotinamide capsules (dose 366 mg/day) after each evening meal in two healthy male volunteers (60 years), the plasma uridine and homocysteine levels were measured on the day before (baseline) and on the last morning on an empty stomach, and the results are shown in table 9 (values are average of two persons).
TABLE 9 uridine and homocysteine content (. Mu.mol/mL)
Run 3.8
After 12 weeks of taking disodium uridylate capsules (dose 500 mg/day), nicotinamide capsules (dose 366 mg/day) and alfa-GPD capsules (dose 300 mg/day) after dinner for two healthy male volunteers (60 years), the plasma uridine and homocysteine levels were measured on the day before (baseline) and on the last morning on an empty stomach and the results are shown in Table 10 (values are average for two persons).
TABLE 10 uridine and homocysteine content (. Mu.mol/mL)
Base line Last day Variation of Increment%
Uridine (uridine) 4.00 6.87 2.87 +71.8
HomocysteineAmmonia acid 11.35 9.95 1.40 -12.3
Run 3.9
After two healthy male volunteers (60 years) took disodium uridylate capsule (dose 500 mg/day), nicotinamide capsule (dose 366 mg/day), alfa-GPD capsule (dose 300 mg/day) and DHA capsule (dose 100 mg/day) 12 weeks after each dinner, the uridine and homocysteine levels in plasma were measured on the pre-day (baseline) and last day morning on an empty stomach, and the results are shown in Table 11 (values are average of two persons).
TABLE 11 uridine and homocysteine content (μmol/mL)
Base line Last day Variation of Increment%
Uridine (uridine) 4.15 7.20 3.05 +73.5
Homocysteine 11.48 9.80 1.68 -14.6
Run 3.10
Two healthy male volunteers (60 years old) took disodium uridylate capsule (dose 500 mg/day), nicotinamide capsule (dose 366 mg/day), alfa-GPD capsule (dose 300 mg/day), DHA capsule (dose 100 mg/day) and B after dinner every day 6 The plasma uridine and homocysteine levels were measured 12 weeks after the capsule (dose 50 mg/day), on the day before administration (baseline) and on the morning on an empty stomach, and the results are shown in Table 12 (values are averages of two persons).
TABLE 12 uridine and homocysteine content (. Mu.mol/mL)
Base line Last day Variation of Increment%
Uridine (uridine) 3.95 7.36 3.41 +86.3
Homocysteine 12.20 9.90 2.30 -18.9
Run 3.11
Two healthy male volunteers (60 years old) took disodium uridylate capsule (dose 500 mg/day), nicotinamide capsule (dose 366 mg/day), alfa-GPD capsule (dose 300 mg/day), DHA capsule (dose 100 mg/day), B after dinner every day 6 Capsules (dose 50 mg/day) and B 12 After 12 weeks of the capsule (dose 1 mg/day), the plasma uridine and homocysteine levels were measured on the morning empty stomach on the day before administration (baseline) and on the last day, and the results are shown in Table 13 (values are averages of two persons).
TABLE 13 uridine and homocysteine content (. Mu.mol/mL)
Base line Last day Variation of Increment%
Uridine (uridine) 4.23 7.95 3.72 +88.0
Homocysteine 12.15 9.70 2.45 -20.2
Run 3.12
Two healthy male volunteers (60 years old) took disodium uridylate capsule (dose 500 mg/day), nicotinamide capsule (dose 366 mg/day), alfa-GPD capsule (dose 300 mg/day), DHA capsule (dose 100 mg/day), B after dinner every day 6 Capsule (dosage 50 mg/day), B 12 After 12 weeks of capsules (dose 1 mg/day) and folic acid capsules (dose 0.4 mg/day), the plasma uridine and homocysteine levels were measured on the morning empty stomach on the day before (baseline) and the last day, and the results are shown in table 14 (values are average of two persons).
TABLE 14 uridine and homocysteine content (μmol/mL)
Base line Last day Variation of Increment%
Uridine (uridine) 4.17 8.25 4.08 +97.8
Homocysteine 12.30 9.60 2.70 -22.0
The above description is only exemplary embodiments of the invention and should not be taken as limiting the scope of the invention. Equivalent alterations, modifications and combinations will be effected by those skilled in the art without departing from the spirit and principles of this invention.

Claims (13)

1. A food or pharmaceutical composition comprising disodium uridylate and optionally food additives or pharmaceutical excipients; preferably, the food additive or pharmaceutical adjuvant comprises other vitamins or minerals.
2. The food composition or pharmaceutical composition according to claim 1, further comprising a compound selected from the group consisting of choline, acetylcholine, phosphatidylcholine, glycerophosphorylcholine, modified soybean phospholipid, nervonic acid, DHA, docosahexaenoic acid lipid, and vitamin B 6 Vitamin B 12 And folic acid.
3. The food or pharmaceutical composition of claim 1, further comprising one or more selected from the group consisting of choline, acetylcholine, phosphatidylcholine, glycerophosphorylcholine, and modified soybean phospholipids.
4. The food or pharmaceutical composition according to claim 1, further comprising one or more selected from choline, acetylcholine, phosphatidylcholine, glycerophosphorylcholine, modified soybean phospholipids; and one or more selected from the group consisting of nervonic acid, DHA and docosahexaenoic acid lipid.
5. The food or pharmaceutical composition according to claim 1, further comprising one or more selected from choline, acetylcholine, phosphatidylcholine, glycerophosphorylcholine, modified soybean phospholipids; one or more selected from the group consisting of nervonic acid, DHA and docosahexaenoic acid lipid; vitamin B 6 。
6. The food or pharmaceutical composition according to claim 1, further comprising one or more selected from choline, acetylcholine, phosphatidylcholine, glycerophosphorylcholine, modified soybean phospholipids; one or more selected from the group consisting of nervonic acid, DHA and docosahexaenoic acid lipid; vitamin B 6 The method comprises the steps of carrying out a first treatment on the surface of the Vitamin B 12 。
7. The food or pharmaceutical composition according to claim 1, further comprising one or more selected from choline, acetylcholine, phosphatidylcholine, glycerophosphorylcholine, modified soybean phospholipids; one or more of nervonic acid, DHA and docosahexaenoic acid lipid; vitamin B 6 The method comprises the steps of carrying out a first treatment on the surface of the Vitamin B 12 The method comprises the steps of carrying out a first treatment on the surface of the Folic acid.
8. The food or pharmaceutical composition of any one of claims 1-7, further comprising one or more selected from nicotinamide, nicotinamide riboside, nicotinamide mononucleotide, and nicotinic acid.
9. Food or pharmaceutical composition according to any one of claims 1-8, for increasing in vivo, in particular brain uridine levels; and/or for reducing homocysteine levels in vivo; preferably also for simultaneously increasing coenzyme I levels in the body, especially in the liver.
10. The food or pharmaceutical composition according to any one of claims 1-9, wherein the food or pharmaceutical composition is in the form of an oral solid or liquid formulation; preferably, the dosage form of the food or pharmaceutical composition comprises a solid beverage, a tablet (e.g., a tabletted candy, a lozenge), a granular formulation, a powder formulation, or a lyophilized formulation;
preferably, the food comprises a nutritional food, or a health food;
preferably, the food composition or pharmaceutical composition unit preparation contains 100 mg-3000 mg disodium uridylate.
11. Use of the food composition according to any one of claims 1-10 as a food for increasing in vivo, in particular brain uridine levels and/or decreasing in vivo homocysteine levels; preferably as a food for increasing in vivo, in particular brain uridine levels, decreasing in vivo homocysteine levels, and simultaneously increasing in vivo, in particular in the liver, coenzyme I levels.
12. Use of a food composition according to any one of claims 1-10 for the preparation of a food for increasing in vivo, in particular brain uridine levels and/or for decreasing in vivo homocysteine levels; preferably, the use in the manufacture of a food product for increasing in vivo, in particular brain uridine levels, decreasing in vivo homocysteine levels, and simultaneously increasing in vivo, in particular in the liver, coenzyme I levels.
13. Use of a pharmaceutical composition according to any one of claims 1-10 for the manufacture of a medicament for increasing in vivo, in particular brain uridine levels and/or for decreasing in vivo homocysteine levels; preferably, the use in the manufacture of a medicament for increasing in vivo, in particular brain uridine levels, decreasing in vivo homocysteine levels, and simultaneously increasing in vivo, in particular in the liver, coenzyme I levels.
CN202210673700.1A 2022-06-15 2022-06-15 Composition containing disodium uridylate and application thereof Pending CN117257821A (en)

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