CN114306357A

CN114306357A - Application of glycyrrhizic acid or its derivative in preparing medicine for treating retinitis

Info

Publication number: CN114306357A
Application number: CN202210070285.0A
Authority: CN
Inventors: 迟玮; 付云昭
Original assignee: Zhongshan Ophthalmic Center
Current assignee: Zhongshan Ophthalmic Center
Priority date: 2022-01-21
Filing date: 2022-01-21
Publication date: 2022-04-12

Abstract

The invention discloses application of glycyrrhizic acid or a derivative thereof in preparing a medicament for treating retinitis. The glycyrrhizic acid or the derivative or the pharmaceutically acceptable salt thereof can effectively reduce the ocular fundus retinal inflammation focus, inhibit the retinal microglial cell activation and the inflammatory reaction, reduce and inhibit the retinal tissue damage and the inflammatory cell infiltration, has the potential for developing a medicament for treating retinitis, and can prevent patients from suffering from diseases such as hypertension, hyperosteogeny and the like caused by hormone medicaments.

Description

Application of glycyrrhizic acid or its derivative in preparing medicine for treating retinitis

Technical Field

The invention belongs to the technical field of biological medicines, and particularly relates to application of glycyrrhizic acid or derivatives thereof in preparation of a medicine for treating retinitis.

Background

Glycyrrhizic Acid (GA) is one of the main components of Chinese medicinal material Glycyrrhrizae radix, and its molecular formula is C₄₂H₆₂O₁₆. Glycyrrhizic acid and its derivatives have wide pharmacological activity, and the activity research mainly comprises: (1) for the treatment and prevention of gastric ulcer, duodenal ulcer and common cold; (2) exerts an antiallergic effect by reducing IL-4 levels; (3) inhibiting tumor progression; (4) lowering plasma cholesterol levels by affecting cholesterol synthesis by accelerating bile acid excretion; (5) has antiviral activity against Flaviviridae; (6) can be used for treating various dermatoses such as psoriasis and psoriasisVitiligo.

Retinitis is the reactive change of retinal tissue to the damage caused by inflammatory factors. The pathological process of the retina includes degeneration of retinal tissue cells, exudation of intravascular components, and proliferative changes. Vascular endothelial autoimmune retinitis is a disease in which retinal tissue is primarily edematous, exudative, and hemorrhagic, and causes varying degrees of visual impairment, often with serious consequences. The disease is mainly common in young and middle-aged people, and the disease course is long and is easy to recur, and the blindness rate is extremely high. At present, the main clinical treatment method of retinitis is to use glucocorticoid and antibiotic to antagonize inflammatory reaction, but long-term use of the hormone is easy to induce diseases such as hypertension, arteriosclerosis, osteoporosis and the like. The exact mechanism of the onset of retinitis is not completely clear, and the development of safe and effective targeted therapeutic drugs is imminent.

Disclosure of Invention

In order to solve the technical problems, the invention provides application of glycyrrhizic acid or derivatives thereof in preparing a medicament for treating retinitis, which can realize effective treatment of retinitis.

In order to achieve the technical purpose, the invention is realized by the following technical scheme:

in a first aspect, the present invention provides the use of glycyrrhizic acid, or a derivative thereof, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment of retinitis.

The pharmaceutically acceptable salt is glycyrrhetate ammonium salt; the ammonium glycyrrhetate can be monoammonium glycyrrhizinate, diammonium glycyrrhizinate or triammonium glycyrrhizinate.

In the application, the medicine also comprises a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier refers to a conventional pharmaceutical carrier in the pharmaceutical field, and can be any suitable physiologically or pharmaceutically acceptable pharmaceutical auxiliary material; preferably, the pharmaceutical excipient is at least one selected from the group consisting of a disintegrant, a diluent, a lubricant, a binder, a wetting agent, a flavoring agent, a suspending agent, a surfactant, a preservative, and the like.

The content of the glycyrrhizic acid or the derivative thereof or the pharmaceutically acceptable salt thereof in the medicine is 2-2.5 mg/ml.

Preferably, in the above application, the drug is selected from one of tablets, capsules, pills, oral liquid preparations, granules, powders or injections.

After the medicine is applied, the inflammation focus of the fundus retina can be reduced, the activation and the inflammatory reaction of the retinal microglia can be inhibited, and the damage of retinal tissues and the infiltration of inflammatory cells can be reduced.

In a second aspect, the present invention also provides a medicament for treating retinitis, which comprises glycyrrhizic acid, or a derivative thereof, or a pharmaceutically acceptable salt thereof. The medicament also comprises a pharmaceutically acceptable carrier.

The invention has the beneficial effects that:

the invention discovers the application of glycyrrhizic acid, or a derivative thereof, or a pharmaceutically acceptable salt thereof in treating retinitis, can effectively reduce the inflammatory focus of fundus retina, inhibit the activation and inflammatory reaction of retinal microglia, reduce and inhibit the retinal tissue injury and inflammatory cell infiltration, has the potential for developing a medicament for treating retinitis, and can prevent patients from suffering from diseases such as hypertension, hyperosteogeny and the like caused by hormone medicaments.

Drawings

FIG. 1 is a diagram showing the influence of the retinal inflammation focus on the fundus of a mouse model of retinitis in an embodiment of the present invention.

FIG. 2 is a graph showing the effects of the activation of the whole layer of microglia on the retina and the inflammatory response in a mouse model of retinitis according to an embodiment of the present invention.

FIG. 3 is a graph showing the effects of retinal tissue damage and inflammatory cell infiltration in mice that are models of retinitis in accordance with the present invention.

Detailed Description

The technical solutions in the present invention will be described clearly and completely with reference to specific embodiments, and it should be understood that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Examples

Preparation of glycyrrhizic acid injection

Weighing glycyrrhizic acid powder 0.1g, placing in 1ml DMSO, standing for dissolving, adding dissolved glycyrrhizic acid into 49ml PBS, and making into glycyrrhizic acid injection 50 ml.

Examples of the experiments

15C 57 mice (18-20g) were randomized into three groups: (1) retinitis group (EAU); (2) glycyrrhizic acid treatment group for retinitis (EAU + GA); (3) control group (NC): normal C57 mice.

The model making mode of the mouse animal model with the retinitis is as follows: mixing IRBP1-20 with Freund's complete adjuvant 1:1, and emulsifying; each mouse in the model was injected subcutaneously with 150. mu.L of IRBP/complete Freund's adjuvant, followed by intraperitoneal injection of 1. mu.g of pertussis toxin.

The mice in the retinitis group are all retinitis model mice; performing glycyrrhizic acid treatment on the immunized retinitis model mouse to obtain a glycyrrhizic acid treatment group for retinitis; the specific treatment method comprises the following steps: on the first day after immunization, the mice of the retinitis model are injected with the glycyrrhizic acid injection every other day and are continuously administered for 21 days. Observing the eyeground of mice in the retinitis glycyrrhizic acid treatment group every 2-3 days after immunization on the 7 th day and scoring; simultaneously observing and scoring the eyeground of the mice in the group of the retinitis; further, fundus images of mice in the control group were used as a control. Fig. 1 is a graph showing the effect of ocular fundus retinal inflammation foci on mice of the retinitis model at day 21 of the experiment, in which the ocular fundus of two mice in each group is shown. In fig. 1, "→" indicates a diseased lesion, and it can be seen that a large area of punctate inflammatory lesions and a small fusion lesion can be seen on the fundus of the retinitis group (EAU) mouse which is not treated with glycyrrhizic acid, and the clinical score is 3 points; the eyeground of the mice in the glycyrrhizic acid treatment group (EAU + GA) for retinitis only has a few punctate lesions, no papilloma edema, no vascular inflammation and the like, and the clinical score is 1. As shown in figure 1, after the treatment by glycyrrhizic acid, the clinical score is obviously reduced, and the eyeground retinal inflammation focus is obviously reduced.

On the 21 st day of the experiment, the mice are sacrificed to take eyeball tissues, paraffin sections are taken, IBA-1 immunofluorescence staining is carried out, and the activation condition of microglia is observed; FIG. 2 is a graph showing the effects of whole retinal layer microglial activation and inflammatory responses. Wherein, the fluorescence staining section of the control group (NC) is used as a control; "→" in fig. 2 indicates a positive staining of microglia; as can be seen from fig. 2, the retinas of the retinitis group (EA U) mice that were not treated with glycyrrhizic acid had a large amount of microglial activation infiltration, while the retinitis glycyrrhizic acid treated (EAU + GA) mice had a significantly reduced microglial infiltration.

On the 21 st day of the experiment, the mice were sacrificed to take eyeball tissues, paraffin sections were taken, HE staining was performed, inflammatory infiltration of the entire retina layer and pathological manifestations such as retinal detachment, granuloma, hemorrhage and the like were observed, and inflammation was scored according to the pathological manifestations and inflammatory cell infiltration. Wherein HE stained section of control group (NC) was used as control; in fig. 3, "→" indicates retinal wrinkles and inflammatory cell infiltrates, and it can be seen that there were many retinal wrinkles and a large amount of inflammatory cell infiltrates in the whole retinal layer of the mice of the retinitis group (EAU) not treated with glycyrrhizic acid, and the pathological section score was 3 points, whereas the retinal whole inflammatory cell infiltrates were reduced, the retinal wrinkles were reduced and the degree was reduced, and the pathological section score was 0.5 point in the mice of the retinitis glycyrrhizic acid treatment group (EAU + GA). As can be seen from fig. 3, the pathological score of the retinal pathological section of the retinitis glycyrrhizic acid-treated group was significantly decreased compared to the untreated retinitis group.

The above description is only an embodiment of the present invention, and not intended to limit the scope of the present invention, and all modifications and equivalents made by the contents of the present invention or directly or indirectly applied to other related technical fields are included in the scope of the present invention.

Claims

1. Use of glycyrrhizic acid, or a derivative thereof, or a pharmaceutically acceptable salt thereof, in the preparation of a medicament for the treatment of retinitis.

2. The use according to claim 1, wherein the pharmaceutically acceptable salt is an ammonium glycyrrhetate salt.

3. The use of claim 1, wherein the medicament further comprises a pharmaceutically acceptable carrier.

4. The use according to claim 1, wherein the glycyrrhizic acid or derivative or pharmaceutically acceptable salt thereof is present in an amount of 2 to 2.5 mg/ml.

5. The use according to claim 1, wherein the medicament is selected from one of a tablet, a capsule, a pill, an oral liquid, a granule, a powder or an injection.

6. The use of claim 1, wherein the medicament is for reducing ocular fundus retinal inflammatory foci, inhibiting retinal microglial activation and inflammatory responses, reducing retinal tissue damage and inflammatory cell infiltration.

7. A medicament for treating retinitis, comprising glycyrrhizic acid, or a derivative or a pharmaceutically acceptable salt thereof.

8. The medicament for treating retinitis according to claim 7, further comprising a pharmaceutically acceptable carrier.