Application of atractylodes lactone II in the preparation of medicines for treating diabetic retinopathy

Abstract

The present invention discloses the use of Atractylodes lactone II in the preparation of a medicament for treating diabetic retinopathy. The use of Atractylodes lactone II disclosed in the present invention in the preparation of a medicament for treating diabetic retinopathy has the following beneficial effects: 1. Through the hypoglycemic, anti-inflammatory, antioxidant, and vascular protective effects of Atractylodes lactone II, a non-invasive, multi-target treatment strategy is provided, and diabetic metabolic disorders and retinal microvascular lesions are simultaneously improved, thereby overcoming the singleness and limitations of existing technologies; 2. Atractylodes lactone II can effectively lower blood sugar in diabetic mice; 3. Atractylodes lactone II can effectively improve glucose tolerance in diabetic mice; 4. Atractylodes lactone II can alleviate vascular occlusion in the retinas of diabetic mice and make the vascular morphology of diabetic mice closer to that of control mice; 5. Atractylodes lactone II can reduce the degree of pathological damage to the retinal tissue of diabetic mice.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine, and particularly relates to the application of atractylodes lactone II in the preparation of a medicine for treating diabetic retinopathy. Background Art

[0002] Diabetic retinopathy (DR) is the most common microvascular complication of diabetes, characterized by retinal vascular leakage, occlusion, and neovascularization, ultimately leading to vision loss. Globally, over 640 million people with diabetes develop DR, a leading cause of blindness in adults. The pathogenesis of DR is closely linked to hyperglycemia-induced oxidative stress, inflammation, overexpression of vascular endothelial growth factor (VEGF), and disruption of the blood-retinal barrier.

[0003] The main treatments for diabetic retinopathy are:

[0004] Drug treatment: 1. Anti-VEGF drugs (such as ranibizumab and bevacizumab): Intravitreal injection inhibits neovascularization and can effectively relieve macular edema. However, repeated injections are required and are costly, leading to high treatment costs, poor patient compliance, and significant side effects with long-term use (possibly leading to complications such as increased intraocular pressure or retinal fibrosis). 2. Microcirculatory-enhancing drugs (such as calcium dobesilate): These drugs work by providing antioxidant benefits and reducing vascular leakage, but their efficacy is limited and they are only suitable for early-stage lesions.

[0005] Laser photocoagulation: It reduces oxygen demand by destroying the peripheral retina and protects macular function, but it will sacrifice part of the visual field and has limited effect on mid- and late-stage lesions.

[0006] Surgical treatment: Vitrectomy is suitable for severe vitreous hemorrhage or retinal detachment, but the surgical risk is high and postoperative visual recovery is limited, especially for mid- to late-stage lesions.

[0007] Traditional Chinese Medicine Treatment: Tongluo Mingmu Capsules: Composed of red peony root and astragalus root, they have an overall efficacy rate of 61% and can improve retinal microcirculation. However, their target of action is unclear, and their efficacy still requires large-scale validation. Furthermore, they lack dual regulation of glucose metabolism and retinal microvascular disease. Tangning Tongluo Tablets: Reduce inflammation by inhibiting the ERS / NF-κB pathway and have been clinically shown to reverse fundus hemorrhages in non-proliferative DR, but long-term safety data are still needed. Summary of the Invention

[0008] Purpose of the invention: The present invention aims to improve the problems existing in the above-mentioned prior art, that is, the present invention discloses the use of Atractylodes lactone II in the preparation of drugs for the treatment of diabetic retinopathy. Existing treatment options for diabetic retinopathy mostly target a single pathological link (such as inhibiting VEGF or improving microcirculation), and are unable to simultaneously address synergistic pathogenic factors such as hyperglycemia, oxidative stress, inflammation, and vascular occlusion. The present invention takes Atractylodes lactone II as the core, combines its known anti-inflammatory and metabolic regulation properties, and applies it to the treatment of diabetic retinopathy for the first time. Through multi-target intervention (hypoglycemic, anti-inflammatory, and vascular protection), it makes up for the shortcomings of the single mechanism of action of the existing scheme, and has the advantages of both the safety of natural medicines and comprehensive efficacy.

[0009] Gaps in the application of natural medicines in retinal protection: Although Atractylodes lactone II has been shown to have anti-inflammatory and metabolic regulatory effects, its specific efficacy and mechanism in diabetic retinopathy have not been explored, and existing technologies do not cover its potential to protect retinal structure and function.

[0010] Technical solution: Use of Atractylodes lactone II as the sole active ingredient in the preparation of a medicament for treating diabetic retinopathy, wherein the structural formula of the Atractylodes lactone II is as follows:

[0011] .

[0012] Furthermore, in the above application, the drug is composed of Atractylodes lactone II and a pharmaceutically acceptable carrier.

[0013] Furthermore, the drug is in the form of tablets, capsules, oral liquids, and granules.

[0014] Furthermore, the tablet is one of ordinary compressed tablets, sugar-coated tablets, effervescent tablets, chewable tablets, multi-layer tablets, sustained-release tablets, and controlled-release tablets.

[0015] Furthermore, the oral liquid preparation is one of a solution, a syrup, an emulsion, and a suspension.

[0016] Furthermore, the granules are one of soluble granules, suspension granules and effervescent granules.

[0017] A drug for treating diabetic retinopathy, comprising atractylodes lactone II as the sole active ingredient, wherein the structural formula of the atractylodes lactone II is as follows:

[0018] .

[0019] The dosage of the above-mentioned drug for treating diabetic retinopathy is 30 to 60 mg / kg.

[0020] Beneficial effects: The use of the Atractylodes lactone II disclosed in the present invention in the preparation of a medicament for treating diabetic retinopathy has the following beneficial effects:

[0021] 1. Through the hypoglycemic, anti-inflammatory, antioxidant, and vascular protective effects of Atractylodes lactone II, this drug provides a non-invasive, multi-target treatment strategy that simultaneously improves diabetic metabolic disorders and retinal microvascular disease, thereby overcoming the singleness and limitations of existing technologies.

[0022] 2. Atractylodes lactone II can effectively lower blood sugar in diabetic mice;

[0023] 3. Atractylodes lactone II can effectively improve glucose tolerance in diabetic mice;

[0024] 4. Atractylodes lactone II can alleviate vascular occlusion in diabetic mice and make the vascular morphology of diabetic mice closer to that of control mice;

[0025] 5. Atractylodes lactone II can reduce the degree of pathological damage to the retinal tissue of diabetic mice. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 Schematic diagram of blood glucose levels in each group of mice.

[0027] Figure 2 Schematic diagram of fasting glucose tolerance of mice in each group.

[0028] Figure 3 Schematic diagram of the area under the fasting glucose tolerance curve of each group of mice.

[0029] Figure 4 Schematic diagram of food intake of mice in each group.

[0030] Figure 5 Schematic diagram of water drinking amount of mice in each group.

[0031] Figure 6 Schematic diagram of PAS staining of the retinas of mice in each group.

[0032] Figure 7 Schematic diagram of H&E staining of the retinas of mice in each group. DETAILED DESCRIPTION

[0033] The specific embodiments of the present invention are described in detail below.

[0034] The "ranges" disclosed herein are defined in the form of lower and upper limits. A given range is defined by selecting a lower limit and an upper limit, and the selected lower and upper limits define the boundaries of the particular range. Ranges defined in this manner can be inclusive or exclusive and can be combined arbitrarily, i.e., any lower limit can be combined with any upper limit to form a range. For example, if a range of 10 to 50 is listed for a particular parameter, it is understood that ranges of 10 to 40 and 20 to 50 are also contemplated. Furthermore, if the minimum range values ​​listed are 1 and 2, and if the maximum range values ​​listed are 3, 4, and 5, then the following ranges are all contemplated: 1 to 3, 1 to 4, 1 to 5, 2 to 3, 2 to 4, and 2 to 5. In this application, unless otherwise specified, the numerical range "a to b" is an abbreviation for any combination of real numbers between a and b, where a and b are real numbers. For example, the numerical range "0 to 5" means that all real numbers between "0 to 5" are listed herein, and "0 to 5" is simply an abbreviation for these numerical combinations.

[0035] Unless otherwise specified, all embodiments and optional embodiments of the present application can be combined with each other to form a new technical solution.

[0036] Unless otherwise specified, all technical features and optional technical features of this application can be combined with each other to form a new technical solution.

[0037] Unless otherwise specified, all steps of the present application may be performed sequentially or randomly, preferably sequentially. For example, the method includes steps (a) and (b), indicating that the method may include steps (a) and (b) performed sequentially, or may include steps (b) and (a) performed sequentially. For example, the method may further include step (c), indicating that step (c) may be added to the method in any order, for example, the method may include steps (a), (b) and (c), or may include steps (a), (c) and (b), or may include steps (c), (a) and (b), etc.

[0038] Unless otherwise specified, the terms "include" and "comprising" used in this application may be open-ended or closed-ended. For example, "include" and "comprising" may mean that other components not listed may also be included or that only the listed components are included.

[0039] Unless otherwise specified, the reaction is carried out at room temperature and pressure.

[0040] Unless otherwise specified, all parts or percentages are by weight.

[0041] In the present invention, all substances used are known substances and can be purchased or synthesized by known methods.

[0042] In the present invention, the devices or equipment used are all conventional devices or equipment known in the art and are commercially available.

[0043] The use of atractylodes lactone II as the sole active ingredient in the preparation of a medicament for treating diabetic retinopathy, wherein the structural formula of the atractylodes lactone II is as follows:

[0044] .

[0045] Furthermore, in the above application, the drug is composed of Atractylodes lactone II and a pharmaceutically acceptable carrier.

[0046] In one embodiment, the drug is in the form of a tablet, which is a conventional compressed tablet. In another embodiment, the drug is in the form of a tablet, which is a sugar-coated tablet. In another embodiment, the drug is in the form of a tablet, which is an effervescent tablet. In another embodiment, the drug is in the form of a tablet, which is a chewable tablet. In another embodiment, the drug is in the form of a tablet, which is a multilayer tablet. In another embodiment, the drug is in the form of a tablet, which is a sustained-release tablet. In another embodiment, the drug is in the form of a tablet, which is a controlled-release tablet.

[0047] In one embodiment, the drug is in the form of a capsule.

[0048] In one embodiment, the drug is in the form of an oral liquid, which is a solution. In another embodiment, the drug is in the form of an oral liquid, which is a syrup. In another embodiment, the drug is in the form of an oral liquid, which is an emulsion. In another embodiment, the drug is in the form of an oral liquid, which is a suspension.

[0049] In one embodiment, the drug is in the form of granules, which are soluble granules. In another embodiment, the drug is in the form of granules, which are suspension granules. In yet another embodiment, the drug is in the form of granules, which are effervescent granules.

[0050] A drug for treating diabetic retinopathy, comprising atractylodes lactone II as the sole active ingredient, wherein the structural formula of the atractylodes lactone II is as follows:

[0051] .

[0052] In one embodiment, the dosage of the drug for treating diabetic retinopathy is 30 mg / kg. In another embodiment, the dosage of the drug for treating diabetic retinopathy is 45 mg / kg. In yet another embodiment, the dosage of the drug for treating diabetic retinopathy is 60 mg / kg.

[0053] Animals: Male SPF C57 mice weighing 18-22 g were selected and used in the experiments after one week of adaptive feeding.

[0054] Reagents: STZ (streptozotocin); Atractylodes lactone II.

[0055] Example 1

[0056] 1.1. Experimental Animal Grouping and Model Establishment:

[0057] Grouping: The mice were randomly divided into control group, model group, low-dose Atractylodes lactone II group (30 mg / kg), and high-dose Atractylodes lactone II group (60 mg / kg), with 10 mice in each group.

[0058] 1.2 Modeling:

[0059] Except for the control group, mice in other groups were injected with STZ (50 mg / kg) via intraperitoneal injection to establish the model. The control group was injected with an equal volume of sodium citrate buffer.

[0060] STZ can selectively destroy pancreatic β cells and induce hyperglycemia in mice, thereby simulating the diabetic state and providing the basic pathological conditions for the occurrence and development of diabetic retinopathy.

[0061] 1.3. Drug administration:

[0062] After the model was successfully established, the mice in the low-dose Atractylodes lactone II group and the high-dose Atractylodes lactone II group were gavaged with the corresponding doses of Atractylodes lactone II, and the model group and the control group were given equal volumes of normal saline for 8 consecutive weeks.

[0063] Example 2: Observation indicators

[0064] 2.1. Blood glucose testing: Blood was collected regularly every week to test the random blood glucose levels of mice in each group and observe the regulatory effect of Atractylodes lactone II on blood glucose.

[0065] 2.2 Fasting glucose tolerance test: During the administration period, fasting glucose tolerance test was performed regularly to understand whether the glucose tolerance of each group of mice was improved.

[0066] 2.3. Behavioral observation: The food intake and water intake of each group of mice were recorded to observe changes in polyphagia and polydipsia.

[0067] 2.4. Retinal Histopathological Examination: After the experiment, the retinal tissues of the mice were removed and subjected to H&E and PAS staining to observe the morphological changes of the retinal tissue and the status of vascular occlusion.

[0068] Example 3: Experimental results

[0069] 3.1. Blood glucose level: Compared with the model group, the random blood glucose levels of mice in the low-dose and high-dose Atractylodes lactone II groups were significantly reduced (P<0.05 or P<0.01), and the high-dose group had a more obvious blood glucose-lowering effect (e.g. Figure 1 shown).

[0070] 3.2 Fasting glucose tolerance test results: The fasting glucose tolerance curves of mice in the low-dose and high-dose Atractylodes lactone II groups showed that their glucose tolerance was significantly improved, with reduced blood glucose peaks and a faster recovery rate to baseline blood glucose levels (e.g. Figure 2 and Figure 3 shown).

[0071] 3.3 Behavioral manifestations: During the administration period, the polyphagia and polydipsia of mice in the low-dose and high-dose Atractylodes lactone II groups gradually decreased. Compared with the model group, the food intake and water intake were significantly reduced (P < 0.05 or P < 0.01). Figure 4 and Figure 5 shown).

[0072] 3.4. PAS staining showed that the retinal vascular occlusion was more serious in the model group mice, while the vascular occlusion was alleviated in the low-dose Atractylodes lactone II group and the high-dose Atractylodes lactone II group, and the retinal vascular morphology was closer to that of the control group (e.g. Figure 6 shown).

[0073] 3.5. Retinal Pathological Changes: H&E staining results showed that the retinal tissues of the model group mice showed obvious pathological changes, such as vascular dilation, exudation, hemorrhage, and disordered ganglion cell arrangement, while the pathological damage of the retinal tissues of the mice in the low-dose Atractylodes lactone II group and the high-dose Atractylodes lactone II group was alleviated (e.g. Figure 7 shown).

[0074] The embodiments of the present invention have been described in detail above, but the present invention is not limited to the above embodiments, and various modifications can be made within the scope of knowledge possessed by those skilled in the art without departing from the spirit of the present invention.

Claims

1. Use of Atractylodes lactone II as the sole active ingredient in the preparation of a medicament for treating diabetic retinopathy, wherein the structural formula of the Atractylodes lactone II is as follows: 。 2. The use according to claim 1, characterized in that The medicine consists of atractylodes lactone II and a pharmaceutically acceptable carrier.

3. The use according to claim 2, characterized in that The drug is in the form of tablets, capsules, oral liquids, and granules.

4. The use according to claim 3, characterized in that The tablet is one of ordinary compressed tablets, sugar-coated tablets, effervescent tablets, chewable tablets, multi-layer tablets, sustained-release tablets, and controlled-release tablets.

5. The use according to claim 3, characterized in that The oral liquid preparation is one of a solution, a syrup, an emulsion, and a suspension.

6. The use according to claim 3, characterized in that The granule is one of soluble granules, suspension granules and effervescent granules.

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