Application of thymosin or derivative thereof and medicine for treating pleasant sensation deficiency type depression

A technology of anhedonia and thymosin, applied in the field of pharmacy, can solve the problems of acute poisoning, disordered balance relationship, anhedonia, etc., achieve good curative effect, improve anhedonia-type depression symptoms, and have no toxic and side effects

Active Publication Date: 2020-12-04
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AI-Extracted Technical Summary

Problems solved by technology

The reduction of DA levels also affects the levels of DOPAC and HVA and thus affects the occurrence of anhedonia
The imbalance of the three systems of 5-HT energy, NE energy and DA energy may lead to the occurrence of anhedonia, and there may also be a disturbance in the balance of the conversion between DA and 5-HT in the central nervous system
[0004] At prese...
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The invention belongs to the field of pharmacology, discloses an application of thymosin or a derivative thereof and a medicine for treating pleasant sensation deficiency type depression, and particularly discloses an application of thymosin or a derivative thereof in preparation of a medicine for treating pleasant sensation deficiency type depression. The invention further discloses a pharmaceutical composition for treating pleasant sensation deficiency type depression, and the pharmaceutical composition comprises a therapeutically effective amount of thymosin or a derivative thereof. According to the invention, systemic administration of thymosin or a derivative thereof, particularly thymosin beta4 or a derivative thereof, is safe, has a good curative effect on pleasant sensation deficiency type depression, and is tolerated by animals including human beings.

Application Domain

Nervous disorderPeptide/protein ingredients

Technology Topic

Systemic administrationMateria medica +7


  • Application of thymosin or derivative thereof and medicine for treating pleasant sensation deficiency type depression
  • Application of thymosin or derivative thereof and medicine for treating pleasant sensation deficiency type depression
  • Application of thymosin or derivative thereof and medicine for treating pleasant sensation deficiency type depression


  • Experimental program(1)

Example Embodiment

[0023] Experimental case
[0024] First, the experimental animals
[0025] Sexually mature female C57BL / 6 mice, body weight (20-22g), were purchased from Experimental Animal Center of Shandong Province (animal quality certification: No.37009200018914, license number: SCXK (Lu) 2,014,000). Rearing environment: Mice were housed four per cage, 22 ± 1 ℃ temperature, 50 ± 10% humidity, 12h light - dark cycle, food and water freely. Feeding and operation of experimental animals are to comply with the relevant provisions of Guangdong Ocean University Laboratory Animal breeding and use.
[0026] Thymosin β4: purchased from Guangzhou Shang Bin biotechnology company.
[0027] Mice maintain powder feed: Guangdong Experimental Animal Center.
[0028] Second, the experimental program
[0029] Laboratory animals repurchase after one week of acclimation, packet random numbers, a total of three sets, as shown in Table 1:
[0030] Table 1. Animal Grouping
[0032] CUMS CUMS + Tβ4 group and the group exposed to stressors, to model processing; Control group under standard feeding environment, stress is not processed.
[0033] All stressors stochastically independent operation, independent operation of two daily stressors, after 9 weeks continuous stress, measured behavior. Stressors are: lack of food overnight to dry overnight, overnight odor, wet litter overnight, single cage overnight, 200rpm / min shaker 1.5h, 50 mL centrifuge tubes bound 1.5h, 4 ℃ low temperature 1.5h, inclined cage overnight, overnight strobe lights, lights and brightly lit circadian 24h, crowded environment 3h, 18 ℃ swimming 10min.
[0034] Third, behavioral experiments
[0035] Sucrose preference test
[0036] 1. Experimental Procedure
[0037] When the train starts, the animals free access to food and two bottles, one containing 1% sucrose solution bottle, the second bottle containing purified water.
[0038] The first day of the experiment mice were freely fed with 19:00 1% sucrose solution bottles and bottles of feed;
[0039] The next experiment mice were freely fed with 19:00 1% sucrose solution bottle and a bottle of water and feed;
[0040] Experimental third 19:00 feed was removed and the solution bottles;
[0041] Experiment Day 19:00 to mice cages and consisting of 1% sucrose solution bottle intake and a bottle of water and feed, 11 night sucrose preference is determined according to the following formula. Wherein the syrup is calculated as the degree of preference:
[0042] Sucrose consumption of sucrose preference = / (sugar + water consumption amount consumed) * 100%
[0043] Experimental results
[0044] like figure 1 Indicated (shown) * P <0.05vs.Control; ## P <0.01vs.CUMS), results showed that: compared with the control group, mice preference CUMS group reduced sugar 11.73%, indicating the animals anhedonia; administering thymosin β4 after treatment, compared with the group CUMS, sucrose preference degree raised 16.21%, indicating that thymosin β4 for CUMS-induced anhedonia extent have reverse effect.
[0045] IV Determination of monoamine neurotransmitters in the brain tissue of mice
[0046] 1. Experimental Procedure
[0047] 1.1 of brain tissue extracts monoamine neurotransmitters
[0048] Solvent configuration: tissue lysate was 0.6mol / L perchloric acid, 0.5mmol / L disodium edetate, 0.1g / LL- mixed aqueous solution of cysteine. Perchloric acid precipitating agent is 1.2mol / L dipotassium hydrogen phosphate, disodium mixed aqueous solution of 2mmol / L EDTA. Citric acid - sodium acetate buffer solution: 50mmol / L citric acid, 50mmol / L sodium acetate, 0.5mmol / L1- heptane sulfonate, 5mmol / L triethylamine, 0.5mmol / L disodium edetate.
[0049] Extraction Step: 4mL brain was weighed out into a centrifuge tube, tissue lysate was added 150 L, sufficiently homogenized, centrifuged at 15min (14000r / min, 4 ℃), the supernatant was centrifuged again. An equal volume of liquid after centrifugation perchloric acid precipitating agent, centrifuged at ice bath for 10min 15min (14000r / min, 4 ℃), filtered through a 0.45μm membrane, the content of the filtrate was analyzed machine. Determination of the type Monoamine neurotransmitters are: dopamine (dopamine, DA), dihydroxyphenylacetic acid (3,4-dihydroxyphenylacetic acid, DOPAC), 5- hydroxytryptamine (5-HT), 5- hydroxy indole acetic acid (5-HIAA), norepinephrine (NE), 3- methoxy -4-hydroxyphenyl glycol (3-methoxy-4-hydroxyphenylglycol, MHPG).
[0050] 1.2 HPLC - Chromatography with Fluorescence Detector Conditions
[0051] Chromatographic conditions: Column Waters C18 column for the (150mm × 4.6mm, 5μm); mobile phase is citric acid - sodium acetate buffer: methanol (87: 13, v / v); flow rate of 1.0mL / min; Injection in an amount of 20 L; emission wavelength of 330nm, an excitation wavelength of 280nm.
[0052] Qualitative and quantitative methods: Retention time by monoamine neurotransmitters qualitative standards of the respective sample peaks; The content of neurotransmitter performed by known standard sample concentration and peak area and peak area of ​​the sample.
[0053] 2. Experimental results
[0054] 2.1 concentration of monoamine neurotransmitters
[0055] like figure 2 ( * P <0.05, *** P <0.001vs.Control; # P <0.05, ## P <0.01vs.CUMS), the results showed that: compared with the control group, 5-HT concentrations CUMS group reduced 19.93%, 5-HIAA concentrations decreased 24.19%, MHPG reduces the concentration of 30.38%, NE reduces the concentration of 27.09%, DOPAC concentration decreased 47.31%, DA concentration tends to decrease, HVA concentration increased 58.48%; after administration of thymosin β4 treatment, compared with CUMS group, 5-HT concentration raised 26.72%, NE concentration raised 38.88%, DOPAC concentration raised 46.54%, NE, DA, DOPAC and 5-HIAA concentrations were the upward trend; showed thymosin β4 chronic stress-induced neurotransmitter deficiency with improved effect.
[0056] 2.1 monoamine neurotransmitters and its metabolites ratio change
[0057] like image 3 ( * P <0.05, ***. P <0.001vs controls (Control); # P <0.05vs.CUMS), the results showed that: compared with the control group, the CUMS group of 5-HT / 5-HIAA ratio of 24.24% and decreased DA / DOPAC ratio increased by 86.91%; after treatment administered Thymosin β4, compared with CUMS group, 5-HT / 5-HIAA ratio raised 30.42%, DA / DOPAC ratio lowered 30.94%, indicating that thymosin β4 cause of chronic stress neurotransmitters and their metabolites disorders with improved effect.
[0058] In the present embodiment, derivatives of thymosin α1 employed thymosin or thymosin [beta] 4, for example, oxidation β4, Gly-Tβ4, Ala-Tβ4 similar results can be obtained.


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