CN118178387A - Application of EGCG-containing pharmaceutical composition in medicine for treating neuritis - Google Patents
Application of EGCG-containing pharmaceutical composition in medicine for treating neuritis Download PDFInfo
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- CN118178387A CN118178387A CN202410382390.7A CN202410382390A CN118178387A CN 118178387 A CN118178387 A CN 118178387A CN 202410382390 A CN202410382390 A CN 202410382390A CN 118178387 A CN118178387 A CN 118178387A
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- pharmaceutical composition
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- CSSYQJWUGATIHM-IKGCZBKSSA-N l-phenylalanyl-l-lysyl-l-cysteinyl-l-arginyl-l-arginyl-l-tryptophyl-l-glutaminyl-l-tryptophyl-l-arginyl-l-methionyl-l-lysyl-l-lysyl-l-leucylglycyl-l-alanyl-l-prolyl-l-seryl-l-isoleucyl-l-threonyl-l-cysteinyl-l-valyl-l-arginyl-l-arginyl-l-alanyl-l-phenylal Chemical compound C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CSSYQJWUGATIHM-IKGCZBKSSA-N 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Neurosurgery (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to the technical field of specific therapeutic activity application of compounds, and particularly relates to application of a pharmaceutical composition containing EGCG in medicines for treating neuritis. The EGCG-containing pharmaceutical composition comprises the following components in percentage by weight: 1-3 parts of EGCG and tartronic acid. The pharmaceutical composition can obviously relieve somatic symptoms of rat neuritis, promote the peripheral nerve potential nerve conduction speed of rats, promote the expression of P62 protein in peripheral nerve tissues at the far ends of limbs of rats, reduce the expression of protein Beclin1 and reduce the expression of tumor necrosis factor-alpha in peripheral nerve tissues of rats.
Description
Technical Field
The invention belongs to the technical field of specific therapeutic activity application of compounds, and particularly relates to application of a pharmaceutical composition containing EGCG in medicines for treating neuritis.
Background
The disclosure of this background section is only intended to increase the understanding of the general background of the invention and is not necessarily to be construed as an admission or any form of suggestion that this information forms the prior art already known to those of ordinary skill in the art.
Neuritis is a neurological disorder commonly referred to as peripheral neuritis, also known as neuralgia. This condition is typically caused by injury, compression or inflammation of the nerve. Neuritis may cause persistent pain, numbness, tingling, and pain exacerbation. Symptoms of neuritis include, but are not limited to: pain, which may be persistent stinging, needle-stick or burning-like pain. Numbness and tingling, and may be perceived as numbness or tingling. Dyskinesias, neuritis may affect muscle function, resulting in dyskinesias or weakness. Motor and paresthesia, the affected area may exhibit paresthesia, such as a change in sensitivity to touch, temperature, or pain. Neuritis can be classified into the following three categories according to the etiology. (1) infectious neuritis: neuritis caused by infection (such as virus, bacteria, etc.), such as peripheral neuritis caused by lyme disease. (2) immune neuritis: inflammation caused by abnormal attack of the immune system on nervous tissue, such as guillain-barre syndrome. (3) traumatic neuritis: neuritis, such as sciatica, is caused by trauma, compression or other mechanical injury.
Liu Mingyan, yao Weifan, zhong Xin, et al, studies have found that EGCG significantly inhibits apoptosis of nerve cells in the brain; EGCG significantly inhibits the TNFα expression level of its intracerebral inflammatory mediators and reduces the expression level of its receptor TNFR1 (EGCG regulates the effect of Lipocalin2 on APP/PS1 transgenic mice by inhibiting TNFR1 [ C ] 2015 the university of senile dementia and cognitive dysfunction associated society of diseases, academy of diseases, 2015: 204-204.).
The Chinese patent with publication number CN114470236A discloses a composite liposome for improving brain cognitive memory and neuroinflammation, which is prepared by simultaneously loading hydrophobic substance curcumin and hydrophilic substance epigallocatechin gallate (EGCG), and on the basis, carrying out surface modification on the liposome by using lactoferrin, adopting hyaluronic acid to further stabilize a system through electrostatic interaction, and has good stability and free radical scavenging efficiency, can obviously inhibit lipopolysaccharide-induced cognitive dysfunction, and is used for improving brain cognitive memory and neuroinflammation.
Chinese patent publication No. CN115778940A discloses a composition of EGCG and L-theanine for promoting nerve cell repair and regeneration, the content of EGCG is 10-50 mu mol/L or 0.458-22.9 mu g/g; the content of L-theanine is 10-100 mu mol/L or 1.74-17.42 mu g/g, EGCG inhibits the stress and inflammation of amyloid A beta 25-35, promotes metabolism, reduces the intervention of the stress of the amyloid A beta 25-35 on the activity of theanine protection cells, and cooperates with the theanine to target and regulate the cell cycle, so that nerve cells keep a resting state under the stress of the amyloid, promote the cell activity and the growth of axons and keep the high-fidelity structure of the cell proteins.
Disclosure of Invention
The invention provides a pharmaceutical composition for treating neuritis, which comprises EGCG and tartronic acid.
According to the result of pharmacodynamics experiments of neuritis rats, the pharmaceutical composition comprises the following components in parts by weight: 1-3 parts of EGCG and tartronic acid.
In one of the experimental groups, the pharmaceutical composition is prepared from the following components in percentage by weight: EGCG and tartronic acid of 1.
In one of the experimental groups, the pharmaceutical composition is prepared from the following components in percentage by weight: EGCG of 2 and tartronic acid.
In one of the experimental groups, the pharmaceutical composition is prepared from the following components in percentage by weight: EGCG and tartronic acid of 1.
In order to facilitate the administration of patients and accurately control the dosage and ensure the curative effect and safety of the medicine, the invention also prepares the pharmaceutical composition containing EGCG into various preparations, and the preparations are prepared from the pharmaceutical composition containing ECGC and pharmaceutically acceptable auxiliary materials. The type of preparation may be granule, oral liquid, tablet, capsule, pill, powder, paste, etc., but is not limited thereto.
According to pharmacodynamic experiments, the invention also improves the application of the pharmaceutical composition containing EGCG in medicines for treating neuritis. Specifically, the neuritis is drug neuritis, the neuritis is mononeuritis and polyneuritis, and the neuritis is neuritis, radiculitis, nerve Cong Yan, nerve trunk inflammation, peripheral neuritis and nerve-myositis.
Depending on the cause, the neuritis is due to one or more of drugs, infections, wounds, autoimmune diseases, metabolic disorders, poisoning, congenital factors.
Compared with the prior art, the invention has the technical effects that:
According to the invention, EGCG and tartronic acid are combined for use, compared with single drug treatment, a synergistic effect is achieved, the effect of treating neuritis is enhanced, the control and recovery of neuritis are promoted, and particularly, the weight ratio of EGCG to tartronic acid is 2-5: 1-3, the effect of treating neuritis is remarkable. Pharmacodynamic experiments show that the pharmaceutical composition containing EGCG can obviously relieve somatic symptoms of rat neuritis, promote the nerve conduction speed of peripheral nerve potential of rats, promote the expression of P62 protein in peripheral nerve tissues at the far ends of limbs of rats, reduce the expression of protein Beclin1 and reduce the expression of tumor necrosis factor-alpha (TNF-alpha) in peripheral nerve tissues of rats.
Drawings
Fig. 1: change curve of body weight of each group of rats.
Fig. 2: peripheral nerve potential nerve conduction velocity of rats in each group.
Fig. 3: expression of P62 protein in distal peripheral nerve tissue of limbs of rats administered for 14 days.
Fig. 4: expression of the protein Beclin1 in distal peripheral nerve tissue of the limb of the rat 14 days after administration.
Fig. 5: expression of tumor necrosis factor-alpha (TNF-alpha) in peripheral nerve tissue of rats.
Detailed Description
The present invention will be further described with reference to examples for the purpose of making the objects and technical aspects of the present invention more apparent, but the scope of the present invention is not limited to these examples, which are only for explaining the present invention. It will be understood by those skilled in the art that variations or equivalent substitutions that do not depart from the spirit of the invention are intended to be included within the scope of the invention.
Pharmacodynamic experiments
The pharmacodynamics data adopts SPSS22.0 software to carry out statistical analysis on the obtained data, and the data is measuredN=10, and P <0.05 is statistically significant, and in the figure, ", P <0.01 is indicated.
In order to verify the application and the action effect of the pharmaceutical composition in treating neuritis diseases, the inventor conducts related pharmacodynamic test research. The pharmaceutical composition only shows a partial dosage ratio, and the weight ratio of EGCG to tartronic acid is 2-5: the same or similar effects are achieved within the range of 1 to 3. The following experimental study is carried out on the basis of the acute toxicity test and the long-term toxicity test to prove the safety of the medicine, and the administration dosage is within the safe dosage range.
1 Material
1.1 Animals:
SD rats, SPF grade, 180-220g, experimental animal license number: SYXK (robust) 2018 0008, and were adapted for one week prior to the experiment.
1.2 Medicament and dosage
Experiment a group: 2.25mg/kg (EGCG), 1.13mg/kg (tartronic acid)
Experiment B group: 3.38mg/kg (EGCG), 2.25mg/kg (tartronic acid)
Experiment C group: 3.38mg/kg (EGCG), 1.13mg/kg (tartronic acid)
Control group: 0.06mg/kg (mecobalamin tablet)
2. Modeling, grouping and administration
2.1 Method of Forming mold
The molding method comprises the following steps: the P257-81 polypeptide was weighed by an electronic balance, and phosphate buffer was added to 100. Mu.l to prepare a polypeptide solution (2 g/l). The polypeptide solution is uniformly mixed with the complete Freund's adjuvant with the same volume, and is emulsified to prepare an antigen emulsion (1 g/l). The antigen emulsion was extracted and injected into the hind limb plantar of the rat, and 50 μl of the antigen emulsion solution was injected into the plantar of each hind limb of the rat, respectively, to induce an EAN rat model.
2.2 Grouping
Rats successfully molded were randomly divided into a model group, an experiment A group, an experiment B group, an experiment C group and a control group, each group comprising 10 rats.
Blank 10 rats were subjected to sham surgery.
2.3 Administration of drugs
The corresponding medicines are respectively given to the experiment A, the experiment B, the experiment C and the control group according to the administration and the dosage of 1.2; the blank group and the model group were administered with an equal amount of physiological saline, and the administration was performed intragastrically for 14d.
3. Project index detection and result analysis
3.1 Rat behavior
TABLE 1 rat behavioral scoring criteria
| Rat behavior | Scoring of |
| Normal state | 0 |
| Weakness of tail and decrease of muscular tension | １~3 |
| Paralysis of hind limb, loss of the everting and regular reflection part | 4~6 |
| Obvious paralysis of hind limb, total disappearance of eversion and regular reflection | 7~9 |
| Paralysis of four limbs | 10~12 |
And observing the disease condition in the same time period every day, and carrying out scoring statistics. The criteria for behavior scoring are shown in table 1.
Table 2 rat behavioural score statistics
% P < 0.01 in comparison to the model group.
Table 2 shows that the neuroinflammation of rats in the invention group A, group B and group C is gradually improved, and the difference is statistically significant (P < 0.01) compared with rats in the model group according to the statistical analysis of the behavior of rats. The pharmaceutical composition of the invention can improve the symptoms of neuritis rats.
3.2 Rat weight changes
The weight of the rat is weighed before molding, and the weight change of the rat is compared on the 5 th day and the 10 th day of molding, the 7 th day and the 4 th day of administration are all weighed in the same time period.
Fig. 1 shows the change curves of the weights of rats, and it can be seen that the weights of rats in a model group, a test group A, a test group B, a test group C and a control group show a decreasing trend before administration, and the weights of rats in the control group slightly recover after administration, but the effect is poor, the weights of rats in the model group drop immediately, the weights of rats in a blank group show an increasing trend, and the weights of rats in the test group A, the test group B and the test group C recover gradually, and basically recover to the initial weights after 14 days of administration, which indicates that the pharmaceutical composition of the invention can improve the uncomfortable symptoms of neuritis rats and enable the rats to recover gradually.
3.3 Study of peripheral nerve potential nerve conduction velocity of rat
14 Days after administration, the rats were anesthetized by intraperitoneal injection, peripheral nerves at the distal ends of the limbs were isolated, stimulation electrodes and recording electrodes were placed along the isolated nerves from the proximal end to the distal end, and nerve conduction velocity CV (m·s-1) =distance/conduction time between the stimulation electrodes and recording electrodes, and the measurement was repeated 10 times to calculate an average value.
FIG. 2 shows peripheral nerve potential nerve conduction velocity of rats in each group. Compared with the model group, the differences of rats in the experiment A group, the experiment B group and the experiment C group have statistical significance (P is less than 0.01). The medicine composition provided by the invention can stimulate the electrical conduction of rat facial nerves and promote nerve recovery.
3.4 Expression of P62 protein and Beclin1 protein in peripheral nerve tissue of rat
The content of P62 protein in distal peripheral nerve tissue of the limb of the rat is detected by adopting an RT-PCR technology, and the expression content of the protein Beclin1 in distal peripheral nerve tissue of the limb of the rat is detected by adopting an immunohistochemical method.
FIG. 3 shows the expression of P62 protein in distal peripheral nerve tissue of limb of rat at 14 days of administration. FIG. 4 shows the expression of the protein Beclin1 in distal peripheral nerve tissue of the limb of the rat at 14 days of administration. Compared with the model group, the differences of rats in the experiment A group, the experiment B group and the experiment C group have statistical significance (P is less than 0.01). Proved by the invention, the pharmaceutical composition can reduce the expression of the Beclin1 protein in the distal peripheral nerve tissue of the rat, raise the level of the P62 protein, participate in the autophagy regulation and control mechanism and promote the peripheral nerve function recovery.
3.5 Expression of tumor necrosis factor-alpha (TNF-alpha) in peripheral nerve tissue of rat
The content of tumor necrosis factor-alpha (TNF-alpha) in peripheral nerve tissue of the rat is detected by adopting an immunohistochemical method.
FIG. 5 shows the expression of tumor necrosis factor-alpha (TNF-alpha) in peripheral nerve tissue of rats administered for 14 days. The TNF-alpha level was reduced in rats in groups A, B and C compared to rats in the model group, and the differences were statistically significant (P < 0.01).
The dosage of the pharmaceutical composition of the present invention to rats is as follows: pharmacodynamics experiments and researches are carried out on EGCG within the range of 2.25-5.64 mg/kg and tartronic acid within the range of 1.13-3.38 mg/kg, and the EGCG has better treatment effect on neuritis model rats within the dosage range. According to calculation, the dosage range is equivalent to the weight ratio of EGCG to tartronic acid of 2-5: 1-3.
In addition, two groups of comparison experiments are also carried out, and the comparison group 1 is: rats were dosed with EGCG 3.38mg/kg, control group 2: the mode of administration of 2.25mg/kg of tartronic acid to rats and the mode of administration are the same as those of the experimental group. Experiments showed that rats of control group 1 were dosed for 14 days: the behavioural score was 6.3.+ -. 1.24, the body weight was 174.62.+ -. 5.44, the peripheral nerve potential nerve conduction velocity was 4.81.+ -. 0.28, the P62 protein in peripheral nerve tissue was 0.012.+ -. 0.0009, the Beclin1 protein was 0.81.+ -. 0.043, and the TNF- α was 0.38.+ -. 0.019. Control group 2 rats: the behavioural score is 8.2+/-1.93, the body weight is 171.05 +/-6.31, the peripheral nerve potential nerve conduction speed is 4.30+/-0.31, the P62 protein in peripheral nerve tissue is 0.008+/-0.0014, the Beclin1 protein is 0.91+/-0.051 and the TNF-alpha is 0.41+/-0.022. As can be seen from comparison with the experimental group, the treatment effect of the comparative group 1 and the comparative group 2 is far inferior to that of the experimental group, and even cannot achieve the treatment and improvement effects.
EGCG-containing pharmaceutical composition preparation
In order to facilitate the administration of patients, accurately control the dosage and ensure the curative effect and safety of the medicine, the invention also prepares the medicine composition containing EGCG into various preparations, and the preparation of the medicine is also an important link and a conventional means in the modern medicine production and clinical application.
EGCG-containing pharmaceutical composition tablet
The formula comprises the following components:
60mg of EGCG, 30mg of tartronic acid, 200mg of starch, 80mg of lactose, 10mg of carboxymethyl starch sodium and 1mg of magnesium stearate.
The preparation method comprises the following steps: mixing EGCG, tartronic acid, starch, lactose, carboxymethyl starch sodium and magnesium stearate, and tabletting.
EGCG-containing pharmaceutical composition granules
The formula comprises the following components:
90mg of EGCG, 60mg of tartronic acid, 60mg of microcrystalline cellulose, 80mg of starch, 40mg of mannitol, 15mg of low-substituted hydroxypropyl methylcellulose and 2mg of magnesium stearate.
The preparation method comprises the following steps:
Mixing EGCG, tartronic acid, starch, microcrystalline cellulose, mannitol, low-substituted hydroxypropyl methylcellulose and magnesium stearate, wetting with ethanol, granulating, drying, and packaging.
EGCG-containing pharmaceutical composition oral liquid
The formula comprises the following components:
EGCG 90mg, tartronic acid 30mg, sodium benzoate 0.01mg, sucrose 5mg, purified water to 15ml.
The preparation method comprises the following steps:
Dissolving EGCG, tartronic acid and sucrose in appropriate amount of purified water, adding sodium benzoate, and adding purified water to 15 ml.
The above-mentioned pharmaceutical composition tablets, granules and oral liquids containing EGCG are only exemplified, and only a part of specific prescriptions and preparation methods are also exemplified, but those skilled in the art can prepare other dosage forms such as capsules, powders and the like according to conventional methods, and the prescriptions, auxiliary materials and preparation methods of the above-mentioned preparations can be replaced or increased or decreased according to general choices.
Claims (10)
1. The EGCG-containing pharmaceutical composition is characterized by comprising the following components in percentage by weight: 1-3 parts of EGCG and tartronic acid.
2. The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is a composition comprising, by weight, 3: EGCG and tartronic acid of 1.
3. The pharmaceutical composition according to claim 1 or 2, characterized in that it comprises, in weight ratio, 3: EGCG of 2 and tartronic acid.
4. The pharmaceutical composition according to claim 1 or 2, wherein the pharmaceutical composition is in a weight ratio of 2: EGCG and tartronic acid of 1.
5. A formulation, characterized in that it is made from the ECGC-containing pharmaceutical composition of claim 1 and pharmaceutically acceptable excipients.
6. The formulation of claim 5, wherein the formulation is a granule, an oral liquid, a tablet, a capsule, a pill, a powder, a paste.
7. Use of a pharmaceutical composition comprising EGCG as claimed in claim 1 in a medicament for the treatment of neuritis.
8. The use according to claim 7, wherein the neuritis is mononeuritis, polyneuritis.
9. The use according to claim 7, wherein the neuritis is neuronal inflammation, radiculitis, nerve Cong Yan, neuritis, peripheral neuritis, neuro-myositis.
10. The use according to claim 7, wherein said neuritis is caused by one or more of a drug, an infection, a wound, an autoimmune disease, a metabolic disorder, a poisoning, an innate factor.
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Non-Patent Citations (3)
| Title |
|---|
| 刘子明: "HPLC法测黄瓜籽中芸香苷、异槲皮苷含量", 食品研究与开发, vol. 36, no. 20, 31 October 2015 (2015-10-31), pages 149 * |
| 姜文娟: "EGCG抑制TNFα/TNFR1介导的Lipocalin2改善神经免疫微环境的作用机制研究", 博士电子期刊, vol. 2022, 15 February 2022 (2022-02-15) * |
| 杨祥伟等: "表没食子儿茶素没食子酸酯的神经系统药理学作用及机制研究进展", 中国现代应用药学, vol. 40, no. 14, 31 July 2023 (2023-07-31), pages 2032 * |
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