Method for delivering drug to brain tissue through lymphatic system

Abstract

Provided is a method for delivering a drug to the brain tissue through the lymphatic system, comprising: P1, dissolving a drug in an aqueous injection to form a drug solution; P2, subcutaneously injecting the drug solution into bilateral upper eyelids of a human body; and P3, the drug solution diffusing into the brain tissue by means of the lymphatic system between the upper eyelids and the brain, wherein the drug is a water-soluble brain nutrition repair drug or a drug for treating brain functional disorders or an immunotherapy, and the injection area is a subcutaneous deep sub-fascia area of the upper eyelids. By means of the connection channel between the subcutaneous lymphatic system of the upper eyelids and the cerebral lymphatic system, the blood-brain barrier can be bypassed to directionally deliver the drug into the brain tissue.

Description

A method for delivering drugs to brain tissue using the lymphatic system Technical Field

[0001] This invention relates to the field of medical technology, and more particularly to a method for delivering drugs to brain tissue using the lymphatic system. Background Technology

[0002] The blood-brain barrier is a protective physiological barrier existing between the blood and brain tissue. The blood-brain barrier is structured in three parts: an inner layer composed of brain capillary endothelial cells and their tight junctions; a middle layer consisting of the basement membrane and perithelial cells; and an outer layer composed of astrocytes and the extracellular matrix. The overlapping of the inner capillary endothelial cells forms a visible or invisible barrier, allowing only essential substances such as oxygen to enter the brain tissue while preventing the invasion of blood and its harmful macromolecules. This maintains the homeostasis of the central nervous system and protects brain tissue from damage caused by metabolic products.

[0003] However, the blood-brain barrier also limits the effective delivery of over 98% of small-molecule drugs and almost all large-molecule drugs to brain lesions. Therefore, how to safely and reversibly open the blood-brain barrier to allow drugs to effectively cross it and enter brain tissue is a research hotspot in the treatment of central nervous system diseases and has important clinical significance.

[0004] Currently, methods for effectively crossing the blood-brain barrier include: preparing prodrugs, opening the tight structure of the blood-brain barrier, or using carrier systems such as antibodies, liposomes, and nanoparticles. In particular, the use of carrier systems such as nanomedicine technology is particularly noteworthy. For example, Chinese invention patent application number 202210229714.4, entitled "Brain-targeting biomimetic nanomedicine delivery system based on detoxifying bacterial membrane encapsulation that can penetrate the blood-brain barrier and its preparation method and application," discloses a brain-targeting biomimetic nanomedicine delivery system. The drug can penetrate the blood-brain barrier and reach the deep brain parenchyma damage area in a targeted manner, exhibiting good biocompatibility and superior delivery efficiency. However, like other nanotechnology drugs, it also suffers from drawbacks such as high cost, complex preparation process, increased probability of side effects, and potential changes in the physical and chemical properties of the drug that may affect its efficacy. These factors greatly limit the application occasions and scope of nanocarrier drugs. Summary of the Invention

[0005] The purpose of this invention is to study a method for delivering drugs to brain tissue using the lymphatic system. The new method overcomes the shortcomings of drug delivery methods using carrier technology, such as high cost, complex preparation process, large side effects, and possible changes in the physical and chemical properties of the drug. It has the advantages of high drug delivery efficiency, simple operation method, small changes in the physical and chemical properties of the drug, and small side effects.

[0006] The technical solution of the present invention is as follows:

[0007] A method for delivering drugs to brain tissue using the lymphatic system, comprising the following steps:

[0008] P1, dissolve the drug in an aqueous injection to form a drug solution;

[0009] P2, inject the drug solution subcutaneously into both upper eyelids of the human body;

[0010] P3, the drug solution diffuses into the brain tissue through the lymphatic system between the upper eyelid and the brain;

[0011] This novel drug delivery method utilizes the connection between the subcutaneous lymphatic system of the upper eyelid and the lymphatic system of the brain to break through the blood-brain barrier and deliver drugs to brain tissue in a targeted manner. The operation is simple, the delivery efficiency is high, and it does not change the physical and chemical properties of the drug, resulting in fewer side effects.

[0012] Preferably, the injection area is the deep subfascial layer under the skin of the upper eyelid. This injection area is rich in lymphatic tissue and is directly connected to the meningeal lymphatic system and interstitial fluid of the brain tissue, which facilitates the rapid delivery of drugs to the brain tissue by crossing the blood-brain barrier.

[0013] Preferably, the drug solvent diffuses into the brain tissue at a rate of 1 to 60 minutes. The drug delivery rate varies in different areas of the brain tissue, and the drug can cover the entire brain tissue after 60 minutes.

[0014] Preferably, the drug is a water-soluble brain-nourishing and repairing drug, a drug for treating brain dysfunction, or an immune drug. The above-mentioned water-soluble drugs can easily bind tightly to proteins in lymphatic tissue, which can improve the drug's bioavailability.

[0015] The beneficial effects of this invention are: it adopts a new drug delivery method, utilizing the connection channel between the subcutaneous lymphatic system of the upper eyelid and the lymphatic system of the brain to break through the blood-brain barrier and deliver drugs to the brain tissue in a targeted manner. The operation method is simple, the delivery efficiency is high, and it does not change the physical and chemical properties of the drug, resulting in fewer side effects. This provides a new route for drug delivery to the brain tissue. Attached Figure Description

[0016] Figure 1 is a schematic diagram of the fluorescent staining agent present in the injection areas of both upper eyelids.

[0017] Figure 2 is a schematic diagram of fluorescent staining agents present on the surface of brain tissue.

[0018] Figure 3 is a schematic diagram of fluorescent staining agents present deep within brain tissue.

[0019] Figure 4 is a schematic diagram of the presence of fluorescent staining agents at the junction of the left and right brain tissues.

[0020] Figure 5 is a schematic diagram of the presence of fluorescent staining agents in the gyri and sulci of brain tissue.

[0021] Figure 6 is a schematic diagram of fluorescent staining agents present in the pituitary gland of brain tissue.

[0022] Figure 7 is a schematic diagram showing the presence of fluorescent staining agents in the brain and cerebellum.

[0023] Figure 8 is a schematic diagram of the presence of fluorescent staining agents in the hypothalamus of brain tissue.

[0024] Figure 9 is a schematic diagram of the presence of fluorescent staining agents in the spinal cord. Detailed Implementation

[0025] The technical solution of the present invention will be further described in detail below through embodiments and in conjunction with the accompanying drawings.

[0026] Example: This example describes a method for delivering drugs to brain tissue using the lymphatic system, as follows:

[0027] P1, dissolve the drug in an aqueous injection to form a drug solution with a fluorescent label;

[0028] P2, inject the drug solution subcutaneously into both upper eyelids;

[0029] P3, the drug solution diffuses into the brain tissue through the lymphatic pathway between the bilateral upper eyelids and the brain tissue;

[0030] The drug is a water-soluble brain nutrition and repair drug. It is injected using a 1ml syringe into the deep subfascial layer under the skin of the upper eyelid. This injection area is rich in lymphatic tissue and is connected to the meningeal lymphatic system and interstitial fluid of the brain tissue, which facilitates the drug's ability to cross the blood-brain barrier and be effectively delivered to the brain tissue.

[0031] To validate this method, a drug delivery experiment was conducted using fresh human specimens as test subjects. The experimental method is as follows:

[0032] Using ICG as a representative drug, a drug solution containing a dye was prepared by combining it with an aqueous injection. This solution was injected into the deep fascia subcutaneous region of the upper eyelids of the human specimen using a 1ml syringe. Fluorescence imaging revealed fluorescence on the epidermis of both upper eyelids, as shown in Figure 1. After a maximum of 60 minutes, the brain tissue of the human specimen was dissected and observed using fluorescence imaging. Fluorescence was found in the superficial and deep layers of the brain tissue, the junctions between the left and right hemispheres, the gyri sulci, the pituitary gland, the cerebellum, the hypothalamus, and the spinal cord, as shown in Figures 2-9. This indicates that the fluorescent dye was fully distributed throughout the brain tissue, demonstrating that the drug successfully crossed the blood-brain barrier and was effectively delivered to various parts of the brain tissue, achieving the experimental objective.

[0033] The above-mentioned human specimen experiments verified an effective method of delivering drugs to brain tissue via specific lymphatic channels. The drug solution is delivered to the brain tissue via subcutaneous injection, utilizing the lymphatic channels that connect the lymphatic system in the subcutaneous deep fascia of the upper eyelid with the meningeal lymphatic system and interstitial fluid of the brain tissue. This successfully overcomes the blood-brain barrier and is characterized by safety, high efficiency, few side effects, low cost, and good adaptability. Furthermore, it does not alter the physical and chemical properties of the drug and has promising application prospects.

[0034] The above description of the present invention is not intended to limit the present invention, nor is the present invention limited to the examples or embodiments described above. Any changes, modifications, additions or substitutions made by those skilled in the art within the scope of the present invention should be considered as protection within the scope of the present invention.

Claims

1. A method for delivering drugs to brain tissue using the lymphatic system, characterized in that, The method includes the following steps: P1, dissolve the drug in an aqueous injection to form a drug solution; P2, inject the drug solution into the subcutaneous area of ​​both upper eyelids of the human body; P3, the drug solution diffuses into the brain tissue through the lymphatic system between the upper eyelid and the brain.

2. The method for delivering drugs to brain tissue using the lymphatic system according to claim 1, characterized in that: The injection area is the deep subfascial layer under the skin of the upper eyelid.

3. The method for delivering drugs to brain tissue using the lymphatic system according to claim 1, characterized in that: The drug solution diffuses into the brain tissue via the lymphatic system at a rate of 1–60 minutes.

4. A method for delivering drugs to brain tissue using the lymphatic system according to claim 1, 2, or 3, characterized in that: The drug is a water-soluble brain-nourishing and repairing drug, a drug for treating brain functional disorders, or an immune-modulating drug.

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