Composition for relieving postoperative pain and application thereof

Abstract

The invention discloses a composition for relieving postoperative pain and application thereof. The composition comprises astragaloside and / or fucoidin, the purity of the astragaloside is at least 98wt%, the fucoidin comprises fucose, uronic acid and monosaccharide, the content of the fucose in the fucoidin is at least 98wt%, and the total content of the uronic acid and the monosaccharide in the fucoidin is lower than 2wt%. The composition composed of astragaloside and fucoidin is orally taken before an operation, neuroinflammation is successfully relieved through combination of astragaloside and fucoidin, and post-operation pain is relieved. The application range of astragaloside and fucoidin is effectively expanded, and it is found for the first time that the composition can be applied to relieving postoperative pain. In addition, the fish oil is added, so that the pain relieving effect of astragaloside and fucoidin can be further improved, and the fish oil has a synergistic effect.

Description

Technical Field

[0001] The present invention relates to a pain treatment medicine and application thereof, and in particular to a composition for relieving postoperative pain and application thereof. Background Art

[0002] Acute postoperative pain is common in clinical practice. Some patients even face persistent postoperative pain, which may progress to chronic postoperative pain. Even with optimized oral opioids and non-opioid adjuvant therapy, patients undergoing surgery still have significant postoperative pain. Acute postoperative pain remains a major medical problem. Surgical trauma can lead to peripheral sensitization of the affected area (increased pain sensitivity of peripheral nerves) and central sensitization (increased sensitivity to afferent input of noxious neurons in the central nervous system), thereby affecting the pain sensitivity of the surgical area and surrounding structures [TJBRENNAN.Pathophysiology of postoperative pain[J].Pain,2011,152(3Suppl):S33-s40.]. Increased nerve pain sensitivity may be induced by surgical tissue damage, inflammatory environment, nerve damage, and the use of opioids during surgery. Among them, neuroinflammation can induce pain sensitization and aggravate postoperative pain. Studies have also found that reducing neuroinflammation can relieve postoperative pain [C QIAN, Y FAN, L ZONG, et al. Opening K (ATP) channels induces inflammatory tolerance and prevents chronic pain [J]. Brain Behav Immun, 2023, 107: 76-86.].

[0003] Fucoidan is a polysaccharide mainly composed of L-fucose and sulfate groups, which is mainly found in the extracellular matrix of marine invertebrates and brown algae. Fucoidan has a wide range of biological functions, including anti-inflammatory, antioxidant, anti-tumor, antiviral and gastrointestinal protection. Fucoidan cannot be digested by gastric and pancreatic enzymes. Most fucoidans can play a protective role against obesity, diabetes, and inflammatory bowel disease by regulating intestinal microbiota after entering the intestine. Fucoidan can increase claudin-1 expression, promote intestinal mucosal regeneration, and increase its intestinal protective function [X LIU, Y ZHANG, W LI, et al. Fucoidan Ameliorated Dextran Sulfate Sodium-Induced Ulcer ative Colitis by Modulating Gut Microbiota and Bile Acid Metabolism [J]. J Agric Fo od Chem, 2022, 70(47): 14864-76.]. Fucoidan can also reshape the structure of the intestinal microbiota, reduce the relative abundance of Bacteroidetes bacteria, increase the ratio of Firmicutes / Bacteroidetes abundance, and prevent pathogenic bacteria from invading the intestinal mucosa. In addition, fucoidan can adjust the ratio of villus length to crypt depth and repair intestinal mucosal damage, which has an indispensable protective effect on the function of the mucosal barrier and intestinal health. In an in vivo study by Shang et al., fucoidan attenuated intestinal microecological imbalance in mice by increasing the abundance of Ruminococcus and Lactobacillus, and also alleviated colon inflammation and dysbiosis by inhibiting IL-1β, IL-6 and TNF-α [L LIU, J XU, Z ZHANG, et al. Metabolic Ho meostasis of Amino Acids and Diabetic Kidney Disease[J]. Nutrients, 2022, 15(1).]. Research by Shi et al. showed that fucoidan increased the abundance of bacteria that can produce short-chain fatty acids (SCFAs), such as Coccoccus and Clostridium butyricum, thereby reducing intestinal mucosal damage [Y WANG, Q WANG, L DUAN, et al. Fucoida n ameliorates LPS-induced neuronal cell damage and cognitive impairment in mice [J]. Int J Biol Macromol, 2022, 222 (PtA): 759-71.]. Studies have shown that fucoidan can relieve neuroinflammation by protecting the intestinal barrier.

[0004] Astragaloside IV is one of the main active ingredients of Astragalus and is widely used in traditional Chinese medicine. Astragaloside IV has multiple pharmacological effects such as immunomodulation, anti-oxidation, and anti-inflammatory. Astragaloside IV can inhibit the release of inflammatory mediators, such as tumor necrosis factor-α and interleukin-6 [J ZHANG, C WU, L GAO, et al. Astragaloside IV derived from Astragalus membranaceus: A research review on the pharmacological effects [J]. Adv Pharmacol, 2020, 87: 89-112.]. Studies have shown that astragaloside IV can regulate K ATP -JNK gap junction signaling pathway alleviates neuropathic pain [WL DAI, L ZHANG, L HAN, et al. Regulation of the K(ATP)-JNK gap junction signaling pathway by immunomodulator astragaloside IV attenuates neuropathic pain[J]. Reg Anesth Pain Med, 2020, 45(12): 955-63.]. In addition, activation of K ATP Channels can relieve neuroinflammation and relieve chronic pain [C QIAN, Y FAN, L ZONG, et al. Opening K (ATP) channels induces inflammatory tolerance and prevents chronic pain [J]. Brain Behav Immun, 2023, 107: 76-86.].

[0005] At present, there is no research on the effects of astragaloside IV and fucoidan on postoperative pain, and there is no specific drug in clinical practice to relieve postoperative pain and further reduce the use of opioids. Summary of the invention

[0006] Purpose of the invention: The purpose of the present invention is to provide a composition to solve the problem of how to relieve postoperative pain. Another purpose of the present invention is to propose an application of the above composition in the preparation of pain relief drugs to solve the problem of how to prepare pain relief drugs.

[0007] Technical solution: A composition described in the present invention comprises astragaloside IV and / or fucoidan.

[0008] Preferably, the purity of astragaloside Ⅳ is at least 98 wt%.

[0009] Preferably, the fucoidan comprises fucose, uronic acid and monosaccharides, the content of fucose in the fucoidan is at least 98 wt %, and the total content of uronic acid and monosaccharides in the fucoidan is less than 2 wt %.

[0010] Preferably, the composition consists of astragaloside IV and fucoidan in a mass ratio of 1-3:1-3.

[0011] Preferably, the composition also comprises fish oil.

[0012] Preferably, the composition comprises 37.5 wt% fish oil and 62.5 wt% fucoidan.

[0013] Preferably, the composition consists of astragaloside IV, fucoidan and fish oil in a mass ratio of 8-16:10-30:5-10.

[0014] The second aspect of the present invention provides a use of the above composition in the preparation of a pain relief drug.

[0015] Preferably, the pain is postoperative pain.

[0016] Beneficial effects: Compared with the prior art, the present invention has the following significant advantages:

[0017] The present invention orally takes a composition composed of astragaloside IV and fucoidan before surgery, successfully relieving neuroinflammation and postoperative pain through astragaloside IV combined with fucoidan. The present invention effectively expands the application scope of astragaloside IV and fucoidan, and for the first time finds that the composition can be used to relieve postoperative pain. In addition, the addition of fish oil can further enhance the pain relief effect of astragaloside IV and fucoidan, and has a synergistic effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 This is the result of the experiment on relieving postoperative pain by single administration of fucoidan;

[0019] Figure 2 The figure shows the experimental results of relieving postoperative pain by administering astragaloside IV and fucoidan alone or in combination;

[0020] Figure 3 This is a graph showing the results of an experiment on relieving postoperative pain by administering astragaloside IV, fucoidan, and fish oil alone or in combination;

[0021] Figure 1 to Figure 3In the table, Control represents the double distilled water group, POP represents the single surgery modeling group, POP+Fuc+AST IV represents the combined treatment of fucoidan + astragaloside IV + surgical modeling, POP+Fuc represents the single treatment of fucoidan + surgical modeling, POP+Pad4- / - represents Pad knockout mice + surgical modeling, POP+AST IV represents the single treatment of astragaloside IV + surgical modeling, POP+Fuc+AST IV+EPA represents the combined treatment of fucoidan + astragaloside IV + fish oil + surgical modeling, and POP+EPA represents the single treatment of fish oil + surgical modeling. DETAILED DESCRIPTION

[0022] The technical solution of the present invention is further described below in conjunction with the accompanying drawings.

[0023] Example 1: A composition is obtained by thoroughly mixing astragaloside IV:fucoidan in a weight ratio of 37.5:62.5.

[0024] In this embodiment, the content of astragaloside IV in the astragaloside IV is 98.5wt%, the fucoidan contains fucose, uronic acid and monosaccharides, the content of fucose in the fucoidan is 98.4wt%, the total content of uronic acid and monosaccharides in the fucoidan is 1.3wt%, and the remainder is impurities.

[0025] The animal experiment on astragaloside IV combined with fucoidan to relieve postoperative pain is as follows:

[0026] Fucoidan and astragaloside IV were dissolved in water to prepare a composite solution, wherein the final concentration of fucoidan was 20 mg / mL, and the final concentration of astragaloside IV was 12 mg / mL.

[0027] The ICR mice were randomly divided into 5 groups, with 10 mice in each group, namely, double distilled water group, single surgery modeling group, surgery + astragaloside IV + fucoidan administration group, surgery + fucoidan administration group, and surgery + astragaloside IV administration group.

[0028] The method of postoperative pain modeling is as follows: after the mice are anesthetized, an incision of about 0.5 cm long is made from the right hind paw of the mouse 0.25 cm away from the heel to the toe, and the ligaments and muscles in the middle of the sole are cut longitudinally, but the origin and attachment of the muscles are kept intact, and the muscles are separated longitudinally with a blunt dissector. After exposing the ligaments and muscles for 30 seconds, the wound is sutured with fine thread. The pain threshold of the model animals is reduced and the difference is significant, indicating that the model is successfully established.

[0029] The specific drug administration process is shown in Table 1:

[0030] Table 1 Dosage regimen for each group

[0031]

[0032]

[0033] The Von Frey test was performed on the wound site on the surgical side of the mouse every day to detect the mechanical pain threshold of the surgical side of the mouse. Figure 2 shown. Figure 2 The results showed that on the 5th to 6th day after modeling, the effect of the combination on alleviating postoperative pain was significantly better than that of the single-dose group.

[0034] Embodiment 2: The rest is the same as Embodiment 1, except that

[0035] The specific drug administration process is shown in Table 2:

[0036] Table 2 Dosage regimen for each group

[0037]

[0038] Pad4- / - represents Pad4 knockout mice.

[0039] The results are as follows Figure 1 As shown, fucoidan can significantly improve postoperative pain.

[0040] Embodiment 3: The rest is the same as Embodiment 1, except that:

[0041] The specific drug administration process is shown in Table 3:

[0042] Table 3 Dosage regimen for each group

[0043]

[0044]

[0045] The concentration of fish oil in the composition solution is 100 mg / mL.

[0046] The results are as follows Figure 3 As shown, the combined administration of fucoidan + astragaloside I + fish oil can significantly improve postoperative pain, and the effect is significantly better than that of the single administration group.

[0047] In summary, Figure 1-3 Von frey data showed that the combination of fucoidan, astragaloside IV and fish oil can significantly relieve postoperative pain.

Claims

1. A composition, characterized in that Contains astragaloside IV and / or fucoidan.

2. The composition according to claim 1, characterized in that The purity of astragaloside IV is at least 98 wt %.

3. The composition according to claim 1, characterized in that The fucoidan contains fucose, uronic acid and monosaccharide, the content of fucose in the fucoidan is at least 98wt%, and the total content of uronic acid and monosaccharide in the fucoidan is less than 2wt%.

4. The composition according to claim 1, characterized in that It is composed of astragaloside IV and fucoidan in a mass ratio of 1-3:1-3.

5. The composition according to claim 1, characterized in that Also contains fish oil.

6. The composition according to claim 5, characterized in that Contains 37.5wt% fish oil and 62.5wt% fucoidan.

7. The composition according to claim 5, characterized in that It consists of astragaloside IV, fucoidan and fish oil in a mass ratio of 8-16:10-30:5-10.

8. Use of the composition according to any one of claims 1 to 7 in the preparation of a pain relief drug.

9. The use according to claim 8, characterized in that: The pain is postoperative pain.

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