Application of Nimbidiol in preparation of medicine for preventing and treating inflammation-induced angiogenesis

Abstract

The invention belongs to the technical field of medicine, and particularly relates to application of Nimbidiol in preparation of medicine for preventing and treating inflammation-induced angiogenesis, Nimbidiol can remarkably inhibit migration, invasion and lumen formation of vascular endothelial cells induced by inflammation conditions, effectively destroy inflammation-condition-induced angiogenesis in an in-vitro simulated body and in an in-vivo model at the same time, and can be used for preparing medicine for preventing and treating inflammation-induced angiogenesis. Therefore, the Nimbidiol can be used for inhibiting angiogenesis induced by inflammation (such as rheumatoid arthritis), and can be used as a novel candidate medicine in developing an anti-angiogenesis strategy for treating rheumatoid arthritis.

Description

Technical Field

[0001] The invention belongs to the field of medical technology, and specifically relates to an application of Nimbidiol in preparing a medicine for preventing and treating inflammation-induced angiogenesis. Background Art

[0002] Angiogenesis refers to the process of forming new blood vessels by sprouting on existing vascular structures. Angiogenesis plays an important role in wound healing, placental formation, and even embryonic development. At the same time, the occurrence of many diseases is closely related to angiogenesis, such as rheumatoid arthritis, cancer, and diabetic retinopathy. Under normal circumstances, angiogenesis is regulated by angiogenesis-promoting factors and angiogenesis-inhibiting factors. In normal human metabolism, the two are balanced and orderly, and regulate each other. Angiogenesis only occurs during specific periods, such as embryo formation, wound repair, and menstrual cycle. However, when diseases such as inflammation occur, growth factors are unbalanced, making the expression or effect of angiogenesis-promoting factors stronger than inhibitors, leading to endothelial cell activation and the formation of angiogenesis phenotype, which causes excessive blood vessel growth and leads to pathological angiogenesis.

[0003] Anti-angiogenic drugs are one of the directions to block the progression of inflammatory lesions. Taking rheumatoid arthritis as an example, currently, the main rheumatoid drug market in China is non-steroidal anti-inflammatory drugs, slow-acting drugs and traditional Chinese medicine. Traditional Chinese medicine has unique advantages in treating rheumatoid arthritis. It is necessary to find pharmacological substances that inhibit angiogenesis from traditional Chinese medicine for anti-rheumatoid arthritis and clarify their mechanism of action so as to better apply them in clinical practice. However, based on the complexity and variability of the pathological mechanism of inflammation-induced angiogenesis, the discovery of drugs requires a long period of design, exploration and testing. At present, no drug with good efficacy has been reported for the treatment of inflammation-induced angiogenesis.

[0004] The Chinese medicine Acer truncatum is the root and vine stem of Celastrus aculeatus Merr. of the Celastraceae family. It is bitter and pungent, cool in nature, and enters the liver and bladder meridians. It has the effects of dispelling wind and dampness, promoting qi and blood circulation, reducing swelling and detoxifying. It is often used in the treatment of rheumatic pain. It is clinically used for rheumatic pain, gout, nephritis, cholecystitis, leukemia and other diseases. At present, there are also studies reporting that the Chinese medicine Acer truncatum has the effect of resisting joint inflammation in animal models of rheumatoid arthritis. Among them, the chemical composition of Acer truncatum is complex and diverse, and the main components include terpenes, flavonoids, alcohol compounds, etc. Among them, Nimbidiol is one of the active ingredients of the rohanane-type diterpenes in Acer truncatum. Summary of the invention

[0005] The purpose of the present invention is to provide a new application of Nimbidiol in medicine, specifically the application of Nimbidiol in preparing a drug for preventing and / or treating inflammation-induced angiogenesis.

[0006] The above-mentioned purpose is achieved by the following technical solutions.

[0007] The first aspect of the present invention provides a use of Nimbidiol as the sole active ingredient in the preparation of a drug for preventing and / or treating inflammation-induced angiogenesis.

[0008] In some embodiments, the inflammatory disease is rheumatoid arthritis.

[0009] In some embodiments, the Nimbidiol targets and inhibits the proliferation of vascular endothelial cells induced by inflammation when used.

[0010] In some embodiments, the Nimbidiol is used to target and inhibit inflammation-induced migration of vascular endothelial cells.

[0011] In some of these embodiments, the Nimbidiol, when used, targets and inhibits inflammation-induced invasion of vascular endothelial cells.

[0012] In some of the embodiments, the Nimbidiol is used to target and inhibit inflammation-induced lumen formation of vascular endothelial cells.

[0013] In some of these embodiments, the Nimbidiol is used to target and inhibit inflammation-induced microangiogenesis in arterial rings.

[0014] In some of the embodiments, the Nimbidiol is used to inhibit inflammation-induced microangiogenesis in chick chorioallantoic membrane.

[0015] In some embodiments, the drug is in the form of an oral preparation or an injection.

[0016] The second aspect of the present invention provides a pharmaceutical composition for preventing and / or treating inflammation-induced angiogenesis, wherein the pharmaceutical composition comprises an active ingredient and a pharmaceutically acceptable excipient, wherein the active ingredient is Nimbidiol.

[0017] In some embodiments, the inflammatory disease is rheumatoid arthritis.

[0018] In some embodiments, the pharmaceutical composition is in the form of an oral preparation or an injection.

[0019] In the present invention, it is discovered for the first time that Nimbidiol can be used as the sole active ingredient to inhibit angiogenesis induced by inflammatory conditions, wherein experiments have verified that Nimbidiol can significantly inhibit the migration, invasion and lumen formation of vascular endothelial cells induced by inflammatory conditions, and effectively destroy angiogenesis induced by inflammatory conditions in in vitro simulations and in vivo models. Therefore, Nimbidiol can be used to inhibit angiogenesis induced by inflammation (such as rheumatoid arthritis), and can be used as a new candidate drug in the development of anti-angiogenesis strategies for the treatment of inflammation (such as rheumatoid arthritis). BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 The effect of Nimbidiol on the activity of HUVECs. Figure 1 A is the chemical structural formula of Nimbidiol; Figure 1 B is the IC of Nimbidiol on HUVECs 50 value; Figure 1 C is the effect of Nimbidiol on TNF-α-induced HUVECs proliferation.

[0021] Figure 2 The effect of Nimbidiol on the migration and invasion of HUVECs induced by TNF-α. Figure 2 A is the effect of Nimbidiol on the horizontal migration ability of HUVECs induced by TNF-α (scratch test); Figure 2 B is the effect of Nimbidiol on the vertical migration ability of HUVECs induced by TNF-α (Transwell experiment); Figure 2 C is the effect of Nimbidiol on the invasion ability of HUVECs induced by TNF-α.

[0022] Figure 3 The effects of Nimbidiol on angiogenesis in vivo and in vitro models. Figure 3 A is the effect of Nimbidiol on TNF-α-induced HUVECs lumen formation; Figure 3 B is the effect of Nimbidiol on TNF-α-induced angiogenesis in vitro (rat artery ring experiment); Figure 3 C is the effect of Nimbidiol on TNF-α-induced angiogenesis in vivo (chicken embryo chorioallantoic membrane experiment). DETAILED DESCRIPTION

[0023] In order to facilitate the understanding of the present invention, the present invention will be described more fully below. The present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the understanding of the disclosure of the present invention more thorough and comprehensive.

[0024] The experimental methods in the following examples without specifying specific conditions are usually carried out under conventional conditions or conditions recommended by the manufacturers. The various commonly used chemical reagents used in the examples are all commercially available products.

[0025] Unless otherwise defined, all technical and scientific terms used in the present invention have the same meaning as those commonly understood by those skilled in the art to which the present invention belongs. The terms used in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The term "and / or" used in the present invention includes any and all combinations of one or more of the related listed items.

[0026] Endothelial cells (human umbilical vein endothelial cells, HUVECs) are one of the key cells in angiogenesis. They are cells attached to the inner layer of the blood vessel wall and are usually in a dormant state in a healthy human body. However, when inflammation occurs, growth factors are unbalanced and these cells can be rapidly activated to form new blood vessels, causing excessive blood vessel growth, thus leading to pathological angiogenesis.

[0027] Nimbidiol is one of the active ingredients of the rhodanese-type diterpenoids in Acer truncatum. Nimbidiol can be extracted and separated from Acer truncatum by conventional extraction technology combined with chromatography or other appropriate separation techniques.

[0028] The embodiment of the present invention provides a use of Nimbidiol as the sole active ingredient in the preparation of a drug for preventing and / or treating inflammation-induced angiogenesis.

[0029] According to the above, the inventors first discovered that Nimbidiol can be used as the only active ingredient to inhibit angiogenesis induced by inflammatory conditions: by establishing an inflammatory model and detecting the effects of Nimbidiol on inflammation-induced HUVECs proliferation, migration, invasion and lumen formation, it was found that Nimbidiol can significantly inhibit the proliferation of vascular endothelial cells induced by inflammatory conditions, and block the key links of angiogenesis: migration, invasion and lumen formation of vascular endothelial cells; at the same time, it effectively destroys angiogenesis induced by inflammatory conditions in vitro simulations and in vivo models. Therefore, the Nimbidiol can be used in the treatment of angiogenesis induced by inflammation, such as rheumatoid arthritis, and can be used as a new candidate drug in the development of anti-angiogenesis strategies for the treatment of rheumatoid arthritis.

[0030] The dosage form of the drug can be an oral preparation, such as a capsule, tablet, etc., or an injection, etc. The pharmaceutical composition containing the active ingredient of the present invention can be formulated into a form suitable for topical, parenteral, oral, pulmonary, intratracheal, intranasal, transdermal or intraduodenal administration. Typical routes of administration are parenteral, intranasal or transdermal administration or administration by inhalation; the active ingredient of the present invention can also be administered parenterally, whether subcutaneously, intravenously, intramuscularly, intrasternal, transdermally or by infusion technology, without particular limitation.

[0031] In certain embodiments of the present invention, a patient suffering from inflammation is treated. The patient can be any animal suffering from inflammation, preferably a mammal, preferably a human. The drug is prepared in a dosage form suitable for children or adults.

[0032] Inflammation may include respiratory tract infection, digestive system infection, skin infection, urinary system infection, arthritis, lymphadenitis, myocarditis, hepatitis, nephritis, fibrinous inflammation, suppurative inflammation, serous inflammation, hemorrhagic inflammation, etc. In a preferred embodiment of the present invention, the inflammation is rheumatoid arthritis.

[0033] The present invention is further described in detail below with reference to specific embodiments.

[0034] Material

[0035] Human umbilical vein endothelial cells (HUVECs) were primary cells extracted and cultured in the laboratory; SPF-grade eggs (chicken embryos) were purchased from Guangzhou Zhongbo Biotechnology Co., Ltd., China; SPF-grade SD rats were purchased from Charles River Company, China; Nimbidiol was purchased from Sigma-Aldrich Company, USA, with the structural formula as shown below: Figure 1 As shown in A; penicillin-streptomycin solution was purchased from Biosharp, China; endothelial cell culture medium ECM was purchased from ScienCell, USA; Matrigel high concentration matrix gel was purchased from BD, USA; CCK-8 kit was purchased from AbMole, USA; Transwell was purchased from Corning, USA; recombinant human TNF-α was purchased from Peprotech, USA.

[0036] Example 1: Effect of Nimbidiol on HUVECs activity

[0037] Cell culture: Human umbilical vein endothelial cells (HUVECs) were cultured in endothelial cell culture medium (ECM) at 37°C in a 5% CO2 incubator.

[0038] Cytotoxicity assay: 1×10 4HUVECs were inoculated in 96-well plates, 100 μL per well, and cultured in a 37°C, 5% CO2 incubator. After the cells were cultured with complete medium for 24 hours, they were divided into the following groups: blank group with only medium, control group with only cells without drugs, and Nimbidiol drug group (2.5, 5, 10, 15, 20, 30, 40, and 50 μM). Each group had 6 replicate wells and was cultured in a 37°C, 5% CO2 incubator for 24 hours. The CCK-8 method was used to detect cell survival. The results are shown in Figure 2. Figure 1 As shown in B, Nimbidiol has the effect of reducing the survival of HUVECs, and its IC 50 It is 26.41μM.

[0039] TNF-α induced HUVECs proliferation experiment: HUVECs were cultured in 96-well plates for 24 hours, the old culture medium was removed, and 5% FBS culture medium (total culture medium volume 100 μL) without or with TNF-α (10 ng / mL) and Nimbidiol (10 μM) was added to different groups of cells, with 6 replicate wells set for each group, and cultured at 37°C, 5% CO2 for 24 hours. The survival was detected by CCK-8 method. The results are shown in Figure 1 As shown in C, TNF-α treatment can significantly stimulate the proliferation of HUVECs. Compared with the proliferation of HUVECs after TNF-α treatment, the survival rate of HUVECs to which TNF-α and Nimbidiol were added was significantly downregulated, indicating that Nimbidiol can inhibit the proliferation of HUVECs induced by TNF-α.

[0040] Example 2: Effect of Nimbidiol on TNF-α-induced HUVECs migration and invasion

[0041] Cell scratch migration experiment: HUVECs were seeded in a 6-well plate. After the cells grew to 90% full, they were treated with 5% FBS culture medium for 6 hours. A 20μL pipette tip was used to make scratches against a ruler. The cells were gently rinsed with PBS twice, and the scratched cells were washed away. Culture medium without or with TNF-α (10ng / mL) and Nimbidiol (10μM) and 1% FBS was added. The plates were placed in a 37°C, 5% CO2 incubator for 18 hours. The plates were observed under an inverted microscope, photographed, and recorded. The results are shown in Figure 2. Figure 2 As shown in A, in the cell scratch test, compared with the TNF-α group, the number of migrating HUVECs in the Nimbidiol-treated group was significantly reduced, proving that Nimbidiol has the effect of weakening the ability of TNF-α-induced horizontal migration of HUVECs.

[0042] Cell chemotaxis migration experiment: Transwell was used to detect the effect of Nimbidiol on the chemotaxis of HUVECs. HUVECs were diluted to a concentration of 2×10 5 600 μL of medium without or with TNF-α (10 ng / mL) and Nimbidiol (10 μM) and 20% FBS was added to the lower chamber of the Transwell. HUVECs (2×10 4 Cells / well) were placed in the upper chamber of the Transwell, and 100 μL of culture medium containing Nimbidiol (10 μM) and 5% FBS was added. Incubate for 14 h at 37°C and 5% CO2, remove the Transwell chamber, remove the cells that have not migrated with a cotton swab, gently rinse with PBS, dry, fix with 4% paraformaldehyde, stain with 0.1% crystal violet, rinse with double distilled water to remove excess crystal violet stain, and dry. Count the cells on the lower surface of the Transwell under a microscope, take pictures and record. The results are shown in Figure 2 As shown in B, a small number of HUVECs in the blank control group underwent autonomous migration; under the induction of TNF-α, the number of cells migrating out of the chamber increased significantly, and the difference was statistically significant compared with the blank control group; after treatment with Nimbidiol, the number of cell migration was significantly reduced compared with the TNF-α group, indicating that Nimbidiol has the effect of weakening the ability of TNF-α-induced HUVECs to vertically migrate.

[0043] Cell invasion assay: 8 h in advance, apply Matrigel matrix gel dilution gel on the upper surface of Transwell and place it at 37°C and 5% CO2 to solidify the matrix gel dilution gel. Take out the pretreated Transwell. Dilute HUVECs to a concentration of 4×10 5 600 μL of medium without or with TNF-α (10 ng / mL) and Nimbidiol (10 μM) and 20% FBS was added to the lower chamber of the Transwell. HUVECs (4×10 4 Cells / well) were placed in the upper chamber of the Transwell, and 100 μL of culture medium containing Nimbidiol (10 μM) and 5% FBS was added. Incubate for 24 hours at 37°C and 5% CO2, remove the Transwell, use a cotton swab to clean the cells and Matrigel that have not invaded the Transwell, rinse gently with PBS, dry, fix with 4% paraformaldehyde, stain with 0.1% crystal violet, rinse the excess crystal violet stain with double distilled water, and dry. Count the cells in the Transwell under a microscope and take pictures for record. The results are shown in Figure 2As shown in C, under the induction of TNF-α, the number of HUVECs invading the chamber increased significantly; while the average number of cells invading the chamber in the Nimbidiol-treated group was significantly reduced compared with the TNF-α group, indicating that Nimbidiol has the effect of reducing the TNF-α-induced HUVECs invasion ability.

[0044] Example 3: Effects of Nimbidiol on Angiogenesis in In Vitro and In Vitro Models

[0045] HUVECs tube formation experiment: Place Matrigel in a 4°C refrigerator overnight to melt, add Matrigel diluted gel to the pre-cooled 96-well plate 8 hours in advance, and place in a carbon dioxide incubator to solidify the Matrigel diluted gel. Take out the pre-treated 96-well plate from the carbon dioxide incubator. 4 HUVECs were added to 96-well plates at 100 cells / well. 5% FBS culture medium without or with TNF-α (10 ng / mL) and Nimbidiol (10 μM) was added to the cells of different groups and cultured at 37°C and 5% CO2 for 8 h. Tube formation was observed under an inverted microscope. Figure 3 As shown in A, TNF-α can increase the number and length of tubes formed by HUVECs; compared with the TNF-α group, Nimbidiol can significantly reduce the number and length of tubes formed by HUVECs, indicating that Nimbidiol can inhibit TNF-α-induced tube formation of HUVECs.

[0046] Rat artery ring experiment: 8h in advance, add Matrigel matrix gel dilution gel to 96-well culture plate, place in 37℃, 5% CO2 incubator, let Matrigel matrix gel solidify, and set aside. Open the rat chest cavity, separate the thoracic aorta, remove the peripheral membrane tissue and fibrous tissue of the aorta, and cut the blood vessel into artery rings with a length of about 1.0-1.5mm. Place the artery ring in a 96-well plate pre-coated with Matrigel matrix gel dilution gel; in addition, carefully add 60μL of pre-melted Matrigel matrix gel dilution gel to cover the blood vessel ring, stand the artery ring upright, and incubate at 37℃, 5% CO2 for 30min to solidify the gel to fix the blood vessel. The experiment was divided into: blank group, TNF-α group (10ng / mL), drug group (10μM Nimbidiol + 100ng / mL TNF-α), and the culture medium volume was 100μL. The artery ring was cultured at 37℃, 5% CO2, and the growth of microvessels was observed every day. The culture medium and drugs were replaced every 3 days. On the 9th day, the culture was terminated, the culture medium was discarded, and PBS was used as the background. The microscopic camera system photographed the rat arterial ring culture system and recorded the growth of microvessels in the rat arterial ring. Figure 3 As shown in B, it can be observed that a large number of endothelial cells migrated outward from the incision of the arterial segment and proliferated around the arterial ring in the TNF-α group, vascular buds grew out from the arterial wall and were arranged compactly, and the new microvessels of the branched microvascular lumen-like structure were dense. The proliferation of endothelial cells around the arterial ring in the Nimbidiol-treated group was reduced; compared with the TNF-α group, the proliferation of endothelial cells was significantly reduced, and the formation of capillary-like structures in the arterial ring was significantly reduced, proving that Nimbidiol can reduce TNF-α-induced microangiogenesis in the arterial ring in vitro.

[0047] Chicken embryo chorioallantoic membrane experiment: The chicken embryos were placed in an incubator at a temperature of 37°C and a humidity of 60-62%. The chicken embryos were ventilated regularly and the position of the chicken embryos was adjusted every 12 hours. On the 5th day, two yolk veins were observed about 0.5 cm in front of the embryo. The area between them was called the avascular zone. A window of about 1.5×1.5 cm was marked in this area and the border was drawn. To ensure the integrity of the shell membrane, a tiny hole was opened above the air chamber, and the concave area of ​​the eggshell was gently lifted using fine tweezers. During this process, about 1-2 mL of sterile PBS buffer was dripped onto the shell membrane to promote its separation from the capsule membrane. A tiny window was opened on the shell membrane above the pseudo-air chamber, and then the shell membrane was carefully removed to expose the chicken embryo chorioallantoic membrane, thereby forming a pseudo-air chamber. Check whether there are other visible injuries besides the exposed chorion to confirm whether the pseudo-air chamber has been successfully created. Cover the pseudo-air chamber with sterile tape to prevent displacement. After two days of incubation, the chicken embryos with intact pseudo-air cells and unaffected growth were randomly divided into treatment groups (blank group, TNF-α group (10 ng / mL), and drug group (10 μM Nimbidiol + 100 ng / mL TNF-α)). Under sterile conditions, the protective film of the window was carefully removed, and then the corresponding concentration of drugs was evenly dripped on the placental chorioallantoic membrane of each group of pseudo-air cells. After the window was re-sealed with sterile tape, the treated chicken embryos were returned to the incubator for incubation. After 48 hours of drug action, the sterile tape was carefully peeled off, and the chicken embryo chorioallantoic membrane culture system was photographed by a microscopic camera system, and the growth of its blood vessels was recorded. The results are as follows: Figure 3 As shown in C, the blood vessels in the blank group grew radially and the blood vessel development was relatively clear; after TNF-α treatment, the main blood vessels grew vigorously and formed obvious collateral circulation; after Nimbidiol treatment, the generated blood vessels were thinner, smaller, and fewer, with a lower blood vessel coverage rate, and even blank areas without angiogenesis appeared, indicating that Nimbidiol can inhibit TNF-α-induced microangiogenesis in the chick embryo chorioallantoic membrane.

[0048] In summary, vascular endothelial cells (human umbilical vein endothelial cells, HUVECs) are one of the key cells in angiogenesis. Therefore, in the above embodiments of the present invention, TNF-α was used to induce HUVECs to establish an inflammatory model, and the CCK-8 method was used to determine the IC of Nimbidiol in HUVECs, one of the key cells in angiogenesis. 50 The effect of Nimbidiol on TNF-α-induced HUVECs proliferation was detected by using scratch migration assay, chemotaxis migration assay, invasion assay and lumen formation assay of HUVECs, as well as rat artery ring and chicken embryo chorioallantoic membrane assay, to detect the effect of Nimbidiol on angiogenesis induced by inflammatory conditions in vivo and in vitro. The results showed that Nimbidiol can significantly inhibit the proliferation of vascular endothelial cells induced by inflammatory conditions, and block the key links of angiogenesis: migration, invasion and lumen formation of vascular endothelial cells; at the same time, it can effectively destroy angiogenesis induced by inflammatory conditions in vitro simulation and in vivo models. Therefore, Nimbidiol can be used in the treatment of angiogenesis induced by inflammation, such as rheumatoid arthritis, and can be used as a new candidate drug in the development of anti-angiogenesis strategies for the treatment of rheumatoid arthritis.

[0049] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0050] The above-mentioned embodiments only express several implementation methods of the present invention, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. Use of Nimbidiol as the sole active ingredient in the preparation of a drug for preventing and / or treating inflammation-induced angiogenesis.

2. The use according to claim 1, characterized in that The inflammation is rheumatoid arthritis.

3. The use according to any one of claims 1 to 2, characterized in that: The Nimbidiol, when applied, targets and inhibits the proliferation of vascular endothelial cells induced by inflammation.

4. The use according to any one of claims 1 to 2, characterized in that: The Nimbidiol, when applied, targets and inhibits the migration of vascular endothelial cells induced by inflammation.

5. The use according to any one of claims 1 to 2, characterized in that: The Nimbidiol, when applied, targets and inhibits inflammation-induced invasion of vascular endothelial cells.

6. The use according to any one of claims 1 to 2, characterized in that: The Nimbidiol, when applied, targets and inhibits inflammation-induced lumen formation of vascular endothelial cells.

7. The use according to any one of claims 1 to 2, characterized in that: The Nimbidiol, when applied, targets and inhibits inflammation-induced microangiogenesis in in vitro arterial rings.

8. The use according to any one of claims 1 to 2, characterized in that: The Nimbidiol, when applied, targets and inhibits inflammation-induced microangiogenesis in the chick chorioallantoic membrane.

9. The use according to any one of claims 1 to 2, characterized in that: The dosage form of the drug is an oral preparation or an injection.

10. A pharmaceutical composition for preventing and / or treating inflammation-induced angiogenesis, characterized in that: The pharmaceutical composition comprises an active ingredient and pharmaceutically acceptable excipients, wherein the active ingredient is Nimbidiol.

Images