Medical use of tyrosol for the preparation of a formulation for reducing the toxic effect of penicillin thiazole acid

Abstract

This invention provides the medical use of tyrosol in the preparation of formulations that reduce the toxicity of penicillin-thiazolic acid (PTA). It discloses a novel medical use of tyrosol in preparing formulations that reduce PTA toxicity. By using tyrosol to prevent and treat the residual toxicity of PTA, unnecessary antibiotic replacement regimens can be avoided, significantly reducing the economic burden. A method for preventing and treating PTA residual toxicity is provided, which can significantly reduce the toxicity of PTA and has good preventive and therapeutic effects. The prevention and treatment of PTA residual toxicity has significant socio-economic implications for controlling the hygiene and quality of animal-derived foods, protecting consumer health, and ensuring industrial production.

Description

Technical Field

[0001] This invention discloses the medical use of tyrosol in the preparation of preparations that reduce the toxicity of penicillin thiazolic acid, which can prevent and treat the toxic effects of penicillin thiazolic acid, and belongs to the field of pharmaceutical preparation technology. Background Technology

[0002] Penicillin thiazolic acid is a direct product of the natural degradation, thermal decomposition, alkaline hydrolysis, and enzymatic hydrolysis of penicillin. It enters the animal body along with penicillin, is metabolized in the liver, and accumulates there. Due to the widespread use of penicillin antibiotics in animal husbandry, large amounts of penicillin and its derivatives remain, seriously endangering public health. Studies have shown that long-term consumption of food containing penicillin thiazolic acid residues can disrupt the normal human flora, induce drug resistance, and cause allergic reactions, thus harming human health.

[0003] The most common harm caused by penicillin is allergic reactions. Penicillin is the most common sensitizing drug, but penicillin is a hapten and does not have antigenicity itself. It cannot directly cause allergic reactions. Instead, it induces the body to produce antibodies by binding with large molecular carriers such as proteins and peptides through its degradation product, penicillin, to form a complete antigen or by polymerizing itself into a large molecular polymer. These antibodies then attach to the surface of mast cells and basophils, causing sensitization. Allergic reactions such as contact dermatitis, hemolytic anemia, serum sickness, and anaphylactic shock can occur, and in severe cases, they can be fatal.

[0004] Despite the numerous potential hazards associated with penicillin, there are few reports on methods for preventing and treating penicillin toxicity.

[0005] Tyrosol, also known as p-hydroxyphenylethanol, is a biophenol widely found in plants of the Rhodiola genus, primarily in foods such as olive oil and wine. It is an ethanol compound with antioxidant and anti-inflammatory properties. It has shown promising pharmacological effects in extending lifespan, treating and preventing oxidative stress, neurological diseases, inflammation and diabetes, and inhibiting drug-resistant Staphylococcus aureus and fungi. Its antioxidant capacity gives it a variety of pharmacological effects, particularly its ability to scavenge highly toxic hydroxyl radicals. It exhibits anti-genotoxic activity and inhibits keratinocyte apoptosis. It also prevents endothelial dysfunction by reducing the expression of cell adhesion molecules and inhibits platelet-induced aggregation. Tyrosol inhibits LDL oxidation, thus it is believed to prevent coronary heart disease and tumor development. Furthermore, tyrosol exhibits anti-inflammatory and anti-allergic effects in vivo by reducing mast cell degranulation and the expression of inflammatory cytokines; therefore, tyrosol holds promise as a treatment for allergic inflammatory diseases. Summary of the Invention

[0006] Given the numerous potential hazards of penicillin, this invention provides the medical use of tyrosol in the preparation of formulations that reduce the toxicity of penicillin.

[0007] The present invention relates to the medical use of tyrosol in the preparation of formulations that reduce the toxicity of penicillin-thiazolic acid, particularly in the formulation of any pharmaceutical preparation containing tyrosol as the active ingredient and containing one or more pharmaceutically acceptable carrier substances and / or excipients.

[0008] This invention verifies the toxicity of penicillin-thiazolic acid (PTA) to mouse testicular epithelial cells (TM4) using a CCK-8 assay. TM4 cells were seeded at a density of 1×10⁴ cells / well in 96-well plates and cultured overnight. TM4 cells were stimulated for 24 hours with PTA concentrations of 0, 0.125, 0.25, 0.5, and 1 mg / ml. The results showed that cell viability gradually decreased with increasing PTA concentration, and significant cytotoxicity was observed at a PTA concentration of 1 mg / ml. Furthermore, different concentrations of tyrosol were used for prevention and treatment of PTA-stimulated TM4 cells. The results showed that tyrosol significantly reduced the toxicity of PTA at concentrations of 25, 50, and 100 μM, with the best effect observed at 100 μM. Therefore, tyrosol is a good drug for preventing and treating residual toxicity of PTA.

[0009] The positive effects of this invention are as follows: It discloses a new medical use of tyrosol in the preparation of drugs that reduce the toxicity of penicillin. By using tyrosol to prevent and treat the residual toxicity of penicillin, unnecessary antibiotic alternatives can be avoided, significantly reducing the economic burden. Due to its high efficacy and low toxicity, penicillin is one of the most favored drugs in veterinary clinical practice. However, because its decomposition products have residual toxicity, producers have had to find other drugs to replace it, which greatly increases production costs. Therefore, finding a method to prevent and treat the residual toxicity of penicillin is urgent. The emergence of tyrosol precisely solves this problem. Studies have shown that tyrosol can significantly reduce the toxicity of penicillin, exhibiting good preventive and therapeutic effects. Preventing and treating the residual toxicity of penicillin has important socio-economic significance for controlling the hygiene quality of animal-derived foods, protecting consumer health, and ensuring industrial production. It provides a good countermeasure to avoid the harm of antibiotic residues to consumers. Attached Figure Description

[0010] Figure 1 This is a toxicity distribution diagram for Experimental Example 1 of the present invention;

[0011] Figure 2 This is a toxicity prevention distribution diagram for Experimental Example 2 of the present invention;

[0012] Figure 3This is a diagram showing the therapeutic effect of Experiment 3 of the present invention. Detailed Implementation

[0013] The present invention is further illustrated by the following embodiments, which are not intended to limit the invention in any way. Any modifications or alterations made to the present invention that are easily implemented by those skilled in the art without departing from the technical solutions of the present invention shall fall within the scope of the claims of the present invention.

[0014] Experimental Example 1

[0015] Toxicity of penicillin-thiazolic acid

[0016] Experimental methods:

[0017] Mouse testicular epithelial cells TM4 were cultured in DMEM / F12 complete medium supplemented with 5% FBS and 1% antibiotic solution. After 2-3 passages, TM4 cells in good growth condition were cultured at a rate of 1×10⁹ / L. 4 Cells were seeded at a density of [number] cells / well in 96-well plates and incubated overnight at 37°C with 5% CO2. After overnight incubation, cells were stimulated for 24 h with concentrations of 0.125, 0.25, 0.5, and 1 mg / ml, respectively, and cell viability was measured using the CCK-8 assay.

[0018] The CCK-8 assay method is as follows: Cells were removed from the incubator, the supernatant from each well of the cell culture plate was discarded, and the cells were gently washed twice with sterile PBS preheated to 37°C. Then, CCK-8 dilution buffer was prepared at a ratio of 10:1 using serum-free DMEM / F12 cell culture medium, with 100 μL added to each well. A zeroing well was also set. The cells were incubated in the cell culture incubator for 30 min to 2 h. After incubation, the OD value of the solution in each well was measured using a microplate reader at a wavelength of 450 nm. Based on the measured OD value, cell viability was calculated using the following formula to obtain the toxic effects of different concentrations of penicillin-1,4-oxazolium on the test cells. The zeroing group included cell culture medium and CCK-8; the experimental group included drug-treated cells, cell culture medium, and CCK-8; and the control group included untreated cells, cell culture medium, and CCK-8. Each group was tested in triplicate, with five replicates.

[0019] Experimental results

[0020] The results showed that, compared with the control group, the cell viability of penicillin gradually decreased with increasing concentration, while the toxic effect on TM4 cells was most significant at 1 mg / ml (see [link to study]). Figure 1 );

[0021] in conclusion:

[0022] Penicillin has a dose-dependent cytotoxic effect on TM4 cells; cell viability gradually decreases with increasing penicillin concentration, with a significant effect only observed at 1 mg / ml; indicating that penicillin has a toxic effect on mouse testicular cells; however, the toxic effect is not significant at low doses.

[0023] Experimental Example 2

[0024] The preventive effect of tyrosol on penicillin-thiazolic acid toxicity

[0025] Experimental methods:

[0026] TM4 cells were seeded at a density of 1×10*4 in 96-well plates. The experiment was divided into four groups: control group, tyrosol group (100 μM), penicillin-thiazolic acid treatment group (1 mg / ml), and treatment group: penicillin-thiazolic acid + tyrosol (25, 50, 100 μM).

[0027] The control group received no treatment. Two hours before penicillin-thiazolic acid stimulation, the cells were pretreated with three different concentrations of tyrosol. Cell viability was measured by the CCK-8 assay 24 hours later. The CCK-8 assay method was the same as above.

[0028] Experimental results:

[0029] The results showed that, compared with the control group, there was no significant difference in cell viability in the tyrosol group alone, while the cell viability in the penicillin-thiazolic acid group was significantly reduced. Compared with the penicillin-thiazolic acid treatment group, the cell viability in the treatment group gradually increased, and the difference was significant; see [link to relevant documentation]. Figure 2 .

[0030] in conclusion:

[0031] Tyrosol exhibits a dose-dependent preventive effect against the toxic effects of penicillin-thiazolic acid. A tyrosol dose of 25 μM significantly restored the cell viability of TM4 cells stimulated by penicillin-thiazolic acid, and cell viability gradually increased with increasing concentration. At a tyrosol dose of 100 μM, the cell viability of TM4 cells approached the normal level of the control group, indicating that tyrosol has a good preventive effect against the toxic effects of penicillin-thiazolic acid.

[0032] Experimental Example 3

[0033] The therapeutic effect of tyrosol on penicillin thiazolic acid toxicity

[0034] Experimental methods:

[0035] TM4 cells were seeded at a density of 1×10*4 in 96-well plates. The experiment was divided into four groups: control group, tyrosol group (100 μM), penicillin-thiazolic acid treatment group (1 mg / ml), and treatment group: penicillin-thiazolic acid + tyrosol group (25, 50, 100 μM).

[0036] The control group received no treatment. The tyrosol group, the penicillin-thiazolic acid treatment group, and the treatment group were treated simultaneously, and cell viability was measured using the CCK-8 assay 24 hours later; the CCK-8 assay method was the same as above.

[0037] Experimental results:

[0038] The results showed that there was no significant difference between the tyrosol group and the control group. The cell viability of the penicillin-thiazolic acid treatment group was significantly reduced. For the treatment group, cell viability gradually increased with increasing tyrosol concentration, with the most significant effect observed at 100 μM (see [link to treatment group]). Figure 3 );

[0039] in conclusion:

[0040] Tyrosol exhibits a dose-dependent therapeutic effect on penicillin-thiazolic acid. At tyrosol concentrations of 25, 50, and 100 μM, tm4 cell viability gradually recovered, reaching normal levels at 100 μM, indicating that tyrosol has a good therapeutic effect on penicillin-thiazolic acid, with the best effect observed at 100 μM.

Claims

1. Medical use of tyrosol in the preparation of formulations that reduce the toxicity of penicillin-thiazolic acid.

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