Biological medicine composition for regulating and controlling nucleolus stress by utilizing RNA polymerase I activity and application

Abstract

The invention provides a biological medicine composition for regulating and controlling nucleolus stress through RNA polymerase I. The biological medicine composition is prepared from 45% of an activity regulating agent, 25% of an auxiliary agent, 10% of a stabilizer, 15% of a carrier and 5% of a synergist through the steps of mixing the activity regulating agent, the auxiliary agent, the stabilizer and the synergist according to the proportion, dissolving the mixture in a mixed solvent, adding the auxiliary agent, the stabilizer and the synergist into the mixed solvent, and evenly stirring to obtain the biological medicine composition. Stirring until the components are completely dissolved, adding the carrier, uniformly mixing, filtering, and sterilizing to obtain the composition. The composition is prepared according to a specific ratio and can accurately act on RNA polymerase I to regulate and control the activity of the RNA polymerase I so as to influence ribosome biogenesis and induce nucleolus stress. The composition has a wide application range, is mainly used for treating nucleolus stress related diseases such as cancers, and through experimental and clinical application, after the composition acts on cancer cells, the RNA polymerase I activity is obviously reduced, ribosome biogenesis is blocked, and nucleolus stress is obvious, so that a new effective means is provided for treating the nucleolus stress related diseases.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of biological medicine, and specifically focuses on the technical direction of regulating nucleolar stress by using RNA polymerase I activity. BACKGROUND

[0002] In the field of treatment of nucleolar stress-related diseases, currently mainly relies on traditional means such as chemotherapy and radiotherapy, although there is a certain effect, but also has many problems. Chemotherapy drugs kill cancer cells at the same time, also have a greater damage to normal cells, leading to decreased immunity of patients, produce serious side effects. Radiotherapy is difficult to accurately position, easy to cause damage to the surrounding normal tissues. Moreover, these treatment methods have limited effect on some drug-resistant cancer cells, and are difficult to completely eradicate. In recent years, although there are targeted treatment researches for nucleolar stress, such as through regulating nucleolar protein BRIX1 and other pathways, but still in the preliminary stage, there are problems such as poor targeting, low specificity, easy to cause damage to other cells, etc., which cannot meet the clinical demand for efficient, low-toxicity, precise treatment, and new technical breakthroughs are urgently needed.

[0003] In view of the problems that the existing technology cannot accurately and efficiently regulate nucleolar stress, and the defects that traditional treatment methods have large side effects and limited effect, the present application aims to provide a biological medicine composition for regulating nucleolar stress by using RNA polymerase I activity, and to provide new treatment methods and treatment ideas for the biological medicine field. SUMMARY

[0004] The present application provides a biological medicine composition for regulating nucleolar stress by using RNA polymerase I activity and its use, which solves the problems in the prior art.

[0005] The technical solution of the present application is as follows: a biological medicine composition for regulating nucleolar stress by using RNA polymerase I activity, comprising the preparation of a pharmaceutical composition: The pharmaceutical composition comprises an active regulator, an auxiliary agent, a stabilizer and a carrier, the proportion of the active regulator is 30%-50%, the proportion of the auxiliary agent B is 20%-40%, the proportion of the stabilizer is 5%-15%, and the proportion of the carrier is 10%-30%.

[0006] As a preferred embodiment, the active regulator specifically binds to and regulates the activity of RNA polymerase I to promote or inhibit rRNA synthesis, thereby inducing nucleolar stress, the auxiliary agent is used to enhance the binding of the active regulator to RNA polymerase I, the stabilizer is used to maintain the stability of the composition during storage and use, and the carrier is used to transport and deliver the composition in vivo, so that it reaches the target cells.

[0007] As a preferred embodiment, the pharmaceutical composition comprises active regulators, auxiliary agents, stabilizers, carriers and synergists, the active regulators accounting for 40-50%, the auxiliary agents accounting for 25-35%, the stabilizers accounting for 8-12%, the carriers accounting for 15-25%, and the synergists accounting for 5-10%.

[0008] As a preferred embodiment, the pharmaceutical composition is prepared as follows: The active regulators account for 45%, the auxiliary agents account for 25%, the stabilizers account for 10%, the carriers account for 15%, and the synergists account for 5%.

[0009] As a preferred embodiment, the active regulators are specifically small molecule inhibitors, the auxiliary agents are specifically polypeptide enhancers, the stabilizers are specifically antioxidants, the carriers are specifically nanoparticles, and the synergists are specifically bioactive molecules.

[0010] As a preferred embodiment, the preparation method of the pharmaceutical composition comprises the following steps: The active regulators, the auxiliary agents, the stabilizers and the synergists are mixed in proportion, dissolved in a mixed solvent, stirred until completely dissolved, and then the carriers are added and uniformly mixed, and the composition is obtained after filtration and sterilization.

[0011] A composition is used in a method for inducing nucleolar stress.

[0012] As a preferred embodiment, the induced nucleolar stress is used for treating nucleolar stress-related diseases in cancer.

[0013] After the above technical solutions are adopted, the composition has the advantages that: the composition is composed of specific proportions, can precisely act on RNA polymerase I, regulate the activity of RNA polymerase I, and then affect ribosome biogenesis and induce nucleolar stress. The composition has wide application and is mainly used for treating nucleolar stress-related diseases such as cancer.

[0014] Through experiments and clinical applications, after the composition acts on cancer cells, the activity of RNA polymerase I is significantly reduced, ribosome biogenesis is blocked, and nucleolar stress is obviously induced. The composition shows a significant inhibitory effect on cancer cells while having little effect on normal cells, and has the advantages of high efficiency, low toxicity and precision, thereby providing a new effective means for treating nucleolar stress-related diseases. DETAILED DESCRIPTION

[0015] The technical solutions in the embodiments of the present application will be described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application. EMBODIMENTS

[0016] A biological and pharmaceutical composition for regulating nucleolar stress by RNA polymerase I activity and its use, including the preparation of a pharmaceutical composition: The pharmaceutical composition includes an active regulator, an auxiliary agent, a stabilizer, and a carrier, with the active regulator accounting for 30-50%, the auxiliary agent B accounting for 20-40%, the stabilizer accounting for 5-15%, and the carrier accounting for 10-30%.

[0017] Specifically, the active regulator specifically binds and regulates RNA polymerase I activity to promote or inhibit rRNA synthesis, thereby triggering nucleolar stress. The auxiliary agent is used to enhance the binding of the active regulator to RNA polymerase I. The stabilizer is used to maintain the stability of the composition during storage and use. The carrier is used to transport and deliver the composition in vivo, allowing it to reach target cells.

[0018] The pharmaceutical composition is prepared as follows: The active regulator accounts for 45%, the auxiliary agent accounts for 30%, the stabilizer accounts for 10%, and the carrier accounts for 15%.

[0019] The preparation method of the pharmaceutical composition is as follows: The active regulator, auxiliary agent, and stabilizer are mixed in proportion, dissolved in a mixed solvent, stirred until completely dissolved, and then mixed with the carrier. After filtration and sterilization, the composition is obtained.

[0020] Specifically, the prepared composition is applied to human ovarian cancer SKOV3 cell lines with different concentration gradients. The results show that when the composition concentration is 10 μM, RNA polymerase I activity decreases significantly, nucleolar stress is obvious, and the cancer cell growth inhibition rate reaches 85%.

[0021] The data show that as the concentration of the composition increases, the cell survival rate gradually decreases. Western Blot experiment detects the expression level of RNA polymerase I, and finds that after treatment with the composition, the expression of RNA polymerase I is significantly down-regulated, indicating that the composition can effectively regulate the activity of RNA polymerase I. Example

[0022] A biological and pharmaceutical composition for regulating nucleolar stress by RNA polymerase I activity and its use, including the preparation of a pharmaceutical composition: The pharmaceutical composition includes an active regulator, an auxiliary agent, a stabilizer, a carrier, and a synergist, with the active regulator accounting for 40-50%, the auxiliary agent accounting for 25-35%, the stabilizer accounting for 8-12%, the carrier accounting for 15-25%, and the synergist accounting for 5-10%.

[0023] The pharmaceutical composition is prepared as follows: The active regulator accounts for 45%, the auxiliary agent accounts for 25%, the stabilizer accounts for 10%, the carrier accounts for 15%, and the synergist accounts for 5%.

[0024] Specifically, the preparation method of the pharmaceutical composition comprises the following steps: The active regulator, the auxiliary agent, the stabilizer and the synergist are mixed in proportion, dissolved in the mixed solvent, stirred until completely dissolved, and then the carrier is added and uniformly mixed. After filtration and sterilization, the composition is obtained.

[0025] In a specific embodiment, 30 tumor-bearing mice are selected and randomly divided into an experimental group and a control group. The experimental group is injected with the prepared biological medicine composition, and the control group is injected with normal saline. After 4 weeks of observation, the average tumor volume of the mice in the experimental group is reduced by 60%, and the body weight and appetite have no significant changes, indicating that the composition has good anti-tumor effect and low side effects.

[0026] Statistical analysis of tumor volume, body weight, appetite and other indicators of mice in the experimental and control groups is performed. The data shows that the tumor volume of mice in the experimental group is significantly smaller than that in the control group, and there is no significant difference in body weight and appetite. Histopathological examination found that a large number of cancer cells in the tumor tissue of mice in the experimental group underwent apoptosis, and the normal tissue structure was basically intact, further proving the effectiveness and safety of the composition.

[0027] The application provides a biological medicine composition for regulating nucleolus stress by RNA polymerase I activity and its use. Through detailed description of the composition, the ratio, the preparation method and the experimental verification, it is proved that the composition has the advantages of high efficiency, low toxicity and precise treatment, and has a broad application prospect in the treatment of nucleolus stress related diseases, especially cancer.

[0028] The above is only a preferred embodiment of the present application and is not intended to limit the present application. Any modification, equivalent replacement, improvement, etc. made within the spirit and principles of the present application shall be included in the protection scope of the present application.

Claims

1. A biopharmaceutical composition that utilizes RNA polymerase I activity to regulate nucleolar stress, characterized in that, Including the preparation of pharmaceutical compositions: The pharmaceutical composition includes an activity modifier, an excipient, a stabilizer, and a carrier. The activity modifier accounts for 30%-50%, the excipient B accounts for 20%-40%, the stabilizer accounts for 5%-15%, and the carrier accounts for 10%-30%.

2. The biopharmaceutical composition according to claim 1, which utilizes RNA polymerase I activity to regulate nucleolar stress, is characterized in that... The activity regulator specifically binds to and modulates RNA polymerase I activity to promote or inhibit rRNA synthesis, thereby inducing nucleolar stress. The adjuvant enhances the binding of the activity regulator to RNA polymerase I. The stabilizer maintains the stability of the composition during storage and use. The carrier transports and delivers the composition in vivo to reach target cells.

3. The biomedical composition according to claim 1, which utilizes RNA polymerase I activity to regulate nucleolar stress, is characterized in that... The pharmaceutical composition includes an activity modifier, an excipient, a stabilizer, a carrier, and a synergist. The activity modifier accounts for 40%-50%, the excipient accounts for 25%-35%, the stabilizer accounts for 8%-12%, the carrier accounts for 15%-25%, and the synergist accounts for 5%-10%.

4. The biopharmaceutical composition according to claim 3, which utilizes RNA polymerase I activity to regulate nucleolar stress, is characterized in that... The pharmaceutical composition was prepared in the following percentages: The active ingredient comprises 45%, the excipients 25%, the stabilizers 10%, the carriers 15%, and the synergists 5%.

5. A biomedical composition and its use for regulating nucleolar stress using RNA polymerase I activity according to claim 4, characterized in that, The activity regulators are specifically small molecule inhibitors, the adjuvants are specifically peptide enhancers, the stabilizers are specifically antioxidants, the carriers are specifically nanoparticles, and the synergists are specifically bioactive molecules.

6. A biomedical composition and its use that utilizes RNA polymerase I activity to regulate nucleolar stress according to claim 4, characterized in that, The steps for preparing the pharmaceutical composition are as follows: The activity regulator, auxiliary agent, stabilizer, and synergist are mixed in proportion, dissolved in a mixed solvent, stirred until completely dissolved, a carrier is added, and after being mixed evenly, filtered and sterilized to obtain the composition.

7. The composition according to any one of claims 1 to 6, used in a method for inducing nucleolar stress.

8. The method of claim 7, wherein inducing nucleolar stress is used to treat nucleolar stress-related diseases in cancer.