Application of snake venom-like tripeptide in preparation of medicine for preventing and / or treating pain

Abstract

The invention relates to application of snake venom-like tripeptide in preparation of a medicine for preventing and / or treating pain, and belongs to the technical field of biological medicine. The invention provides an application of snake venom-like tripeptide in preparation of a medicine for preventing / or treating pain. Research finds that after injection administration and transdermal administration, the snake venom-like tripeptide can significantly inhibit pain caused by non-inflammation and non-muscle spasm, which is specifically embodied in that in a hot plate analgesia experiment, subcutaneous injection of the snake venom-like tripeptide can significantly improve the pain threshold of an ICR mouse; in a spiny frog reflex experiment, the medicine composition obtained through compatibility of transdermal drug delivery snake venom tripeptide can remarkably reduce the foot contraction frequency of brain-removed frogs. Therefore, the snake venom-like tripeptide has great application prospects in preparation of drugs for preventing / or treating pain, especially pain caused by non-inflammation and non-muscle spasm.

Description

Technical Field

[0001] The invention relates to application of a snake venom-like tripeptide in preparing a medicine for preventing and / or treating pain, and belongs to the technical field of biomedicine. Background Art

[0002] Pain is an unpleasant physical sensation and emotional experience caused by one or more factors such as inflammation, tissue damage, and nerve damage. When pain occurs, it is often accompanied by negative emotions, sleep disorders, or functional disorders. Pain not only brings physical discomfort to people, but also causes certain troubles to people's lives and mental health, such as decreased quality of life, increased psychological pressure, social difficulties, and increased economic burden. Therefore, it is necessary to pay attention to the problem of pain and actively seek its treatment.

[0003] At present, pain can be relieved through treatments such as medication, physical therapy, surgical treatment and psychotherapy. Among them, medication is one of the most commonly used methods. Pain can be relieved by oral medication or topical ointment (such as non-steroidal anti-inflammatory drugs, analgesics and local anesthetics, etc.); physical therapy is the use of physical means to relieve pain and is conducive to recovery. For example, massage can promote blood circulation and relieve muscle pain. Physical therapy can stimulate nerves and muscle tissues through electrotherapy, ultrasound and other means to relieve pain. Hot compress can dilate blood vessels, promote blood circulation and relieve pain. Cold compress can reduce tissue inflammation and relieve pain. There are also some surgical treatments, such as stellate ganglion block, minimally invasive surgery and other methods to block or remove pain-causing substances to relieve or treat pain; psychotherapy is to help patients learn skills to cope with pain through psychological counseling, cognitive behavioral therapy and other means, enhance their sense of control over pain, and reduce fear and worry about pain.

[0004] However, these treatments also have some shortcomings. First, drug therapy may have some side effects, such as drug dependence and addiction, and needs to be used reasonably under the guidance of a doctor. Secondly, physical therapy requires professionals to perform the operation. If it is not performed properly, it may cause other problems, and each treatment is very inconvenient. Thirdly, the cost of surgical treatment is relatively high, and a series of recovery problems may arise after surgery. Finally, psychotherapy requires time and patience. Patients need to communicate and train with therapists many times to achieve the desired effect. It is slow to take effect and the analgesic effect is general. Therefore, it is urgent to find a treatment method that is easy to use, reasonably priced, quick to take effect, has a good analgesic effect and is non-addictive to relieve pain, so as to make up for the shortcomings of existing treatment methods.

[0005] Snake venom is a liquid secreted from the venom glands of venomous snakes, which mainly helps venomous snakes to hunt and digest food. The composition of snake venom is very complex, including neurotoxins, blood circulation toxins, cytotoxins, mixed toxins, procoagulant components, anticoagulant components and some enzymes. The toxicity, pharmacology and toxicological effects of different venomous snake venoms have their own characteristics, which vary with the snake species. As for neurotoxins, they can be divided into two types according to the site of action and mode of action. One is to act on the presynaptic membrane of the neuromuscular junction and inhibit the release of acetylcholine in the presynaptic membrane, which is called presynaptic neurotoxin. The other is to act on the postsynaptic membrane at the junction of motor nerves and skeletal muscles, causing skeletal muscle relaxation, which is called postsynaptic neurotoxin.

[0006] Tropidolaemus Wagleri is a member of the genus Tropidolaemus of the family Viperidae. The venom of Tropidolaemus Wagleri contains four venom peptides (Waglerins 1 to Waglerins 4). Studies have shown that Waglerin 1, one of the four venom peptides, can inhibit the end plate response of mice to acetylcholine. When Waglerin 1 in the venom enters the human body, it binds to the N-type acetylcholine receptor (nAChR) at the neuromuscular junction, preventing the chemical neurotransmitter acetylcholine from binding to the receptor, thereby blocking muscle excitation. It is a postsynaptic neurotoxin among neurotoxins.

[0007] SYN-AKE is a reversible muscle-type nicotinic acetylcholine receptor (nAChR) antagonist developed based on a short amino acid sequence in the snake venom peptide Waglerin 1. It is also a unique synthetic tripeptide derivative that simulates the activity of snake venom. Studies have shown that when applied topically to the skin as a cosmetic active ingredient, SYN-AKE will also produce the effect of blocking neuromuscular excitation transmission, but the effect will not be as strong as snake venom. It will only block the excitation transmission between nerves and muscles in a small amount, and it is not addictive. SYN-AKE binds to the ε subunit of the nicotinic acetylcholine receptor on the postsynaptic membrane, so that the nicotinic acetylcholine (ACh) released from the presynaptic membrane cannot bind to the nicotinic acetylcholine receptor, causing the nicotinic acetylcholine receptor to close, the nerve excitation transmission to fail, and the local blockage of the nerve transmission muscle contraction signal to relax the muscle, thereby reducing the frequent muscle contraction at the application site and the expression lines and dynamic lines caused by it, thereby achieving the effect of reducing and lightening wrinkles. Because it simulates the mechanism of action of snake venom, it is also called snake venom peptide, snake venom tripeptide, and is often referred to as snake venom peptide.

[0008] At present, many studies have explored the mechanism of action of snake venom peptides in relieving some pain. For example, there is a certain relationship between anti-inflammation and analgesia. Excessive or persistent inflammatory response can cause pain. Anti-inflammatory drugs can effectively control the inflammatory response, reduce symptoms such as tissue redness, swelling, heat and pain, and reduce pain. Therefore, anti-inflammatory drugs usually have a certain analgesic effect. According to literature reports, snake venom tripeptides can regulate the TGF-B / Smad pathway to inhibit the release of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), thereby reducing the inflammatory response. In addition, snake venom tripeptides can also inhibit the migration and proliferation of inflammatory cells, reduce the number of inflammatory cells, and thus relieve inflammatory symptoms. It can be seen that snake venom tripeptides may be able to achieve a certain analgesic effect in pain caused by inflammation. At the same time, excessive neuromuscular excitation can easily lead to excessive muscle tension, which in turn causes muscle spasms. Muscle spasms are often accompanied by severe pain. Therefore, muscle relaxants usually also have a certain analgesic effect. Studies have shown that snake venom tripeptides can reduce the excitability of neuromuscular. It can be seen that snake venom tripeptide may be able to relieve pain caused by muscle spasm. However, there are no reports on whether snake venom tripeptide has analgesic effect on other types of pain commonly seen in clinical practice, and whether the external application of snake venom tripeptide has analgesic effect. Summary of the invention

[0009] In order to solve the above problems, the present invention provides the use of a snake venom-like tripeptide in the preparation of a drug for preventing and / or treating pain.

[0010] In one embodiment of the present invention, the pain includes pain caused by non-inflammation and non-muscle spasm.

[0011] In one embodiment of the present invention, the pain includes neuralgia, muscle pain, joint pain, shoulder and neck pain, pain caused by disease, pain caused by physical injury and / or pain caused by chemical injury.

[0012] In one embodiment of the present invention, the ingredients of the drug include snake venom tripeptide, Chuanxiong root extract, Notopterygium wilfordii extract, Safflower extract, Angelica dahurica extract, Aucklandia lappa extract, Centella asiatica extract, Codonopsis pilosula extract, Licorice extract, Ginseng extract and Artemisia argyi extract.

[0013] In one embodiment of the present invention, the ingredients of the drug further include a thermal agent, oil-soluble capsicum, a solubilizer, menthol, borneol, ethanol, oil-soluble azone, propylene glycol and water.

[0014] In one embodiment of the present invention, the amount of the snake venom tripeptide added to the medicine is 1-50 mg / kg, the amount of the Chuanxiong root extract added to the medicine is 50-400 mg / kg, the amount of the Notopterygium wilfordii extract added to the medicine is 10-600 mg / kg, the amount of the safflower extract added to the medicine is 1-600 mg / kg, the amount of the Angelica dahurica extract added to the medicine is 5-800 mg / kg, the amount of the costusroot extract added to the medicine is 10-600 mg / kg, the amount of the Centella asiatica extract added to the medicine is 100-800 mg / kg, the amount of the Codonopsis pilosula extract added to the medicine is 10-600 mg / kg, the amount of the licorice extract added to the medicine is 10-100 mg / kg, the amount of the ginseng extract added to the medicine is 10-600 mg / kg, and the amount of the Artemisia argyi extract added to the medicine is 10-600 mg / kg.

[0015] In one embodiment of the present invention, the amount of the thermal agent added to the drug is 10-100 mg / kg, the amount of the oil-soluble capsaicin added to the drug is 1-40 mg / kg, the amount of the solubilizer added to the drug is 100-1600 mg / kg, the amount of the menthol added to the drug is 100-500 mg / kg, the amount of the borneol added to the drug is 20-100 mg / kg, the amount of the ethanol added to the drug is 500-2000 mg / kg, the amount of the oil-soluble azone added to the drug is 80-400 mg / kg, the amount of the propylene glycol added to the drug is 1000-4500 mg / kg, and the amount of water added to the drug is 1000-6000 mg / kg.

[0016] In one embodiment of the present invention, the thermal agent includes vanillyl butyl ether, oil-soluble capsaicin and / or capsaicinol; the solubilizer includes CO40, polysorbates and / or polyoxyethylene fatty acid esters.

[0017] In one embodiment of the present invention, the drug is an external analgesic or an injectable analgesic.

[0018] In one embodiment of the present invention, the topical analgesic is an topical central analgesic or an topical peripheral analgesic; the injectable analgesic is an injectable central analgesic or an injectable peripheral analgesic.

[0019] In one embodiment of the present invention, the dosage form of the drug is a transdermal preparation; the transdermal preparation includes a spray, a liniment, a tincture, an oil, an ointment, a paste, a film coating, a film, a gel and / or a nipple tablet.

[0020] The present invention also provides a medicine for preventing and / or treating pain, wherein the ingredients of the medicine include the snake venom-like tripeptide.

[0021] In one embodiment of the present invention, the pain includes pain caused by non-inflammation and non-muscle spasm.

[0022] In one embodiment of the present invention, the pain includes neuralgia, muscle pain, joint pain, shoulder and neck pain, pain caused by disease, pain caused by physical injury and / or pain caused by chemical injury.

[0023] In one embodiment of the present invention, the ingredients of the drug include snake venom tripeptide, Chuanxiong root extract, Notopterygium wilfordii extract, Safflower extract, Angelica dahurica extract, Aucklandia lappa extract, Centella asiatica extract, Codonopsis pilosula extract, Licorice extract, Ginseng extract and Artemisia argyi extract.

[0024] In one embodiment of the present invention, the ingredients of the drug further include a thermal agent, oil-soluble capsicum, a solubilizer, menthol, borneol, ethanol, oil-soluble azone, propylene glycol and water.

[0025] In one embodiment of the present invention, the amount of the snake venom tripeptide added to the medicine is 1-50 mg / kg, the amount of the Chuanxiong root extract added to the medicine is 50-400 mg / kg, the amount of the Notopterygium wilfordii extract added to the medicine is 10-600 mg / kg, the amount of the safflower extract added to the medicine is 1-600 mg / kg, the amount of the Angelica dahurica extract added to the medicine is 5-800 mg / kg, the amount of the costusroot extract added to the medicine is 10-600 mg / kg, the amount of the Centella asiatica extract added to the medicine is 100-800 mg / kg, the amount of the Codonopsis pilosula extract added to the medicine is 10-600 mg / kg, the amount of the licorice extract added to the medicine is 10-100 mg / kg, the amount of the ginseng extract added to the medicine is 10-600 mg / kg, and the amount of the Artemisia argyi extract added to the medicine is 10-600 mg / kg.

[0026] In one embodiment of the present invention, the amount of the thermal agent added to the drug is 10-100 mg / kg, the amount of the oil-soluble capsaicin added to the drug is 1-40 mg / kg, the amount of the solubilizer added to the drug is 100-1600 mg / kg, the amount of the menthol added to the drug is 100-500 mg / kg, the amount of the borneol added to the drug is 20-100 mg / kg, the amount of the ethanol added to the drug is 500-2000 mg / kg, the amount of the oil-soluble azone added to the drug is 80-400 mg / kg, the amount of the propylene glycol added to the drug is 1000-4500 mg / kg, and the amount of water added to the drug is 1000-6000 mg / kg.

[0027] In one embodiment of the present invention, the thermal agent includes vanillyl butyl ether, oil-soluble capsaicin and / or capsaicinol; the solubilizer includes CO40, polysorbates and / or polyoxyethylene fatty acid esters.

[0028] In one embodiment of the present invention, the drug is an external analgesic or an injectable analgesic.

[0029] In one embodiment of the present invention, the topical analgesic is an topical central analgesic or an topical peripheral analgesic; the injectable analgesic is an injectable central analgesic or an injectable peripheral analgesic.

[0030] In one embodiment of the present invention, the dosage form of the drug is a transdermal preparation; the transdermal preparation includes a spray, a liniment, a tincture, an oil, an ointment, a paste, a film coating, a film, a gel and / or a nipple tablet.

[0031] The technical solution of the present invention has the following advantages:

[0032] The present invention provides the use of a snake venom tripeptide in the preparation of a drug for preventing / or treating pain. Studies have found that after injection and transdermal administration, the snake venom tripeptide can significantly inhibit pain caused by non-inflammation and non-muscle spasm, which is specifically reflected in: in the hot plate analgesia experiment, subcutaneous injection of a snake venom tripeptide can significantly increase the pain threshold of ICR mice; in the spinal frog reflex experiment, the pharmaceutical composition obtained by transdermal administration of a snake venom tripeptide can significantly reduce the number of foot retractions of decerebrated frogs. Therefore, the snake venom tripeptide has great application prospects in the preparation of drugs for preventing / or treating pain, especially pain caused by non-inflammation and non-muscle spasm.

[0033] Further, the ingredients of the drug include snake venom tripeptide, chuanxiong root extract, notopterygium root extract, safflower extract, angelica root extract, costus root extract, centella asiatica extract, codonopsis root extract, licorice extract, ginseng extract and wormwood leaf extract. The present invention is compatible with Chinese medicine extracts with the effects of reducing swelling and relieving pain, clearing heat and relieving itching, and combined with snake venom tripeptide to prepare a snake venom tripeptide pharmaceutical composition for various chronic pain, traumatic injuries and the like. Among them, chuanxiong root promotes blood circulation and qi, dispels wind and relieves pain; notopterygium root disperses and relieves pain; safflower promotes blood circulation and menstruation, removes blood stasis and relieves pain; angelica root dispels wind and dampness, dispels cold and relieves pain; costus root promotes qi and relieves pain; centella asiatica clears heat and dampness, detoxifies and reduces swelling; codonopsis root promotes blood circulation and improves microcirculation; licorice clears heat and detoxifies, relieves acute pain, and harmonizes various medicines; ginseng inhibits bacteria and inflammation, increases the nutrient supply of the skin to prevent dryness and dehydration of the skin, and increases the elasticity of the skin; wormwood leaf is used externally to remove dampness and relieve itching. Studies have shown that after transdermal administration, the combination of the present invention has a better effect in inhibiting pain caused by non-inflammatory and non-muscle spasm (in the spinal frog reflex experiment, compared with the single administration of the snake venom tripeptide, the transdermal administration of the combination drug can significantly reduce the onset time of the analgesic effect and prolong the duration of the analgesic effect). In addition, the combination of the present invention can effectively reduce the dosage of the snake venom tripeptide, thereby reducing the cost of the drug.

[0034] Further, the composition of the medicine also includes a heat-sensing agent, oil-soluble capsicum, a solubilizing agent, menthol, borneol, ethanol, oil-soluble azone, propylene glycol and water. The heat-sensing agent, oil-soluble capsicum and oil-soluble azone added by the pharmaceutical composition are commonly used in pharmaceutical external preparations. Wherein, the heat-sensing agent in the additive is composed of some capsicum extracts or other irritating ingredients (capsaicin, vanillyl butyl ether, etc.), which is a substance that can cause the skin or mucous membrane to feel hot, and plays the role of promoting local blood circulation, relieving pain, and relieving muscle fatigue; oil-soluble capsicum is a medicine with capsicum extract as the main ingredient, which has strong irritation and local anesthetic effect, and can change the conduction of pain signals by stimulating the skin nerve endings, so as to achieve the effect of relieving pain; oil-soluble azone has obvious transdermal penetration-assisting effect and can effectively inhibit the growth of bacteria and fungi, and reduce inflammatory reactions. The above materials jointly assist the snake venom tripeptide to promote drug penetration, antibacterial and pain relief. Borneol and menthol added to the medicine have a refreshing feeling. When applied topically, it can reduce redness and swelling, relieve itching and discomfort caused by allergies, inflammation, etc. CO40 is an emulsifier used in medicine and cosmetics. It can promote the stability of oil-water mixtures, make substances that are not easily miscible be evenly dispersed in the preparation, and can also increase its consistency and delay the release of drugs. Propylene glycol is not only a good solvent but also has less irritation to the skin. It is suitable for all types of skin and can relieve discomfort symptoms such as sensitivity and redness. It can quickly penetrate the skin, provide a lasting moisturizing effect, maintain skin moisture balance, and improve dry and rough skin conditions. Studies have shown that after transdermal administration, the pharmaceutical composition of the present invention has a better effect in inhibiting pain caused by non-inflammatory and non-muscle spasm (in the spinal frog reflex experiment, compared with the single application of the snake venom tripeptide, the transdermal administration of the pharmaceutical composition can significantly reduce the onset time of the analgesic effect, and at the same time, prolong the duration of the analgesic effect), and the pharmaceutical composition of the present invention can effectively reduce the dosage of the snake venom tripeptide, thereby reducing the cost of the drug. DETAILED DESCRIPTION

[0035] The following examples are provided for a better understanding of the present invention, but are not intended to limit the best mode of implementation, nor to limit the content and protection scope of the present invention. Any product identical or similar to the present invention obtained by anyone under the inspiration of the present invention or by combining the features of the present invention with other prior arts shall fall within the protection scope of the present invention.

[0036] If no specific experimental steps or conditions are specified in the following examples, the conventional experimental steps or conditions described in the literature in the field can be used. If no manufacturer is specified for the reagents or instruments used, they are all conventional reagent products that can be purchased commercially.

[0037] Experimental Example 1: Hot Plate Analgesia Experiment

[0038] The hot plate analgesia test is a commonly used experimental method in analgesic drug screening. It indirectly evaluates the pain threshold of animals by measuring the reaction time of animals to thermal stimulation. This experimental example explores the analgesic effect of snake venom tripeptide through the hot plate analgesia test. The experimental process is as follows:

[0039] ICR mice (female, 20-22g, purchased from Hangzhou Ziyuan Biotechnology Co., Ltd.) were placed on a hot plate at a temperature of 55±0.2℃, and the latency of ICR mice to lick their hind paws was used as a pain response index, i.e., the pain threshold. The basal pain threshold of each mouse was measured before administration, and mice with a pain threshold of more than 30 seconds were eliminated. ICR mice with qualified pain thresholds were subcutaneously injected with snake venom tripeptide (injection dose 5 mg / kg, the drug was dissolved in saline at a dose of 0.5 mg / mL and then administered, and the snake venom tripeptide used was purchased from Shanghai Yuanye Biotechnology Co., Ltd.), and the pain threshold was measured before injection and at 1, 2, 3, 4, 5, 6, and 7 hours after injection. If the mouse had no pain response on the hot plate for 60 seconds, it was counted as 60 seconds. The measurement results are shown in Table 1. Among them, the control group mice were injected with the same dose of saline as the snake venom tripeptide injection group mice.

[0040] As shown in Table 1, compared with the control group, the pain threshold of mice tended to increase 2 hours after subcutaneous injection of 5 mg / kg of snake venom tripeptide, that is, the snake venom tripeptide began to take effect, and the pain threshold of mice increased significantly at 4 hours, 5 hours, and 6 hours after administration (P<0.05, P<0.01, P<0.01, respectively). The pain threshold of mice decreased significantly 7 hours after administration, at which time, the analgesic effect of the snake venom tripeptide disappeared.

[0041] Table 1 Pain threshold of hot plate analgesia test (X±S, n=7)

[0042]

[0043]

[0044] Note: *: P<0.05; **: P<0.01 (compared with the control group)

[0045] Experimental Example 2: Spinal Frog Reflex Experiment

[0046] The frog whose brain is cut off and the rest of the frog remains basically intact is called a spinal frog. When the skin of the spinal frog is stimulated by dilute hydrochloric acid, the receptors on the skin generate nerve impulses, which are transmitted to the spinal cord along the afferent nerves. After being processed by the spinal cord, they are transmitted to the effector - the skeletal muscles of the hind limbs along the efferent nerves. The skeletal muscles then contract and cause the frog to have a leg flexion reflex. This experimental example explores the analgesic effect of snake venom tripeptide through the spinal frog reflex experiment. The experimental process is as follows:

[0047] The spinal frog reflex test was prepared according to Table 2: Drug composition 1, drug composition 2, drug composition 3, drug composition 4, drug composition 5, drug composition 6, drug composition 7 and drug composition 8 (wherein, Chuanxiong root extract, Notopterygium root extract, safflower extract, Angelica dahurica extract, costus root extract, Centella asiatica extract, Codonopsis root extract, Licorice extract, Ginseng extract and Artemisia argyi extract were purchased from Xi'an Ruilin Biotechnology Co., Ltd.); 90 frogs (purchased from the Animal Purchasing Center of Soochow University) were randomly divided into 9 groups, 10 in each group, and the 9 groups were respectively saline group, drug composition group 1, drug composition group 2, drug composition group 3, drug composition group 4, drug composition group 5, drug composition group 6, drug composition group 7 and drug composition group 8. The experiment started after the grouping was completed. During the experiment, the frog's upper jaw and brain were cut off at the level of both eyes, and its lower jaw was hooked and suspended on an iron bracket. One foot (1 / 2 of the sole) was soaked in 0.05N hydrochloric acid aqueous solution for 10 seconds. If there was a leg retraction reaction within 10 seconds, it was qualified, and those without reaction were eliminated. After each stimulation, it was rinsed with distilled water; the other sole of the frog with qualified leg retraction reaction was completely immersed in the intervention solution for 2 minutes to allow the intervention solution to evenly adhere to the frog's foot surface, and then the frog's sole was taken out. After the frog's sole was taken out of the intervention solution for 1 minute, 10 minutes, 30 minutes and 2 hours, the same sole was repeatedly soaked in 0.05N hydrochloric acid aqueous solution once, and the presence or absence of leg retraction reaction after soaking was recorded. The results are shown in Table 3. Among them, the frogs in the normal saline group used normal saline as the intervention solution, and the frogs in the drug composition group 1, drug composition group 2, drug composition group 3, drug composition group 4, drug composition group 5 and drug composition group 6 used drug composition 1, drug composition 2, drug composition 3, drug composition 4, drug composition 5, drug composition 6, drug composition 7 and drug composition 8 as the intervention solution, respectively (after the intervention solution was added to the beaker, the frogs' feet were soaked in the beaker).

[0048] As shown in Table 3, physiological saline, pharmaceutical composition 1, pharmaceutical composition 2 and pharmaceutical composition 4 all failed to play an analgesic role. Among them, pharmaceutical composition 1 and pharmaceutical composition 4 both used a large amount of snake venom tripeptide, which may be due to the fact that this experiment adopted transdermal administration, and pharmaceutical composition 1 and pharmaceutical composition 4 could not be absorbed through the skin after transdermal administration. Compared with physiological saline, pharmaceutical composition 1, pharmaceutical composition 2 and pharmaceutical composition 4, pharmaceutical composition 3, pharmaceutical composition 5, pharmaceutical composition 6, pharmaceutical composition 7 and pharmaceutical composition 8 all played a certain analgesic role. Among them, pharmaceutical composition 5 had the best analgesic effect. It played an analgesic role 1 minute after applying frog feet, and significantly inhibited the foot withdrawal reaction caused by hydrochloric acid. The analgesic time could last up to 2 hours. Although the analgesic effects of pharmaceutical composition 6, pharmaceutical composition 7 and pharmaceutical composition 8 were not as good as those of pharmaceutical composition 5, they were also better than those of pharmaceutical composition 3. This result shows that appropriate Chinese medicine compatibility can effectively enhance the analgesic effect of snake venom tripeptide after transdermal administration and prolong the duration of analgesia. Moreover, after Chinese medicine compatibility, the dosage of snake venom tripeptide was significantly reduced, which is helpful to reduce the cost of drugs.

[0049] Table 2 Formulation of the pharmaceutical composition

[0050]

[0051]

[0052] Table 3 Analgesic effect of different drug combinations on frog skin

[0053]

[0054]

[0055] Note: *: P<0.05; **: P<0.01 (compared with normal saline group)

[0056] Obviously, the above embodiments are merely examples for the purpose of clear explanation, and are not intended to limit the implementation methods. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementation methods here. The obvious changes or modifications derived therefrom are still within the scope of protection of the invention.

Claims

1. Use of a snake venom-like tripeptide in the preparation of a drug for preventing and / or treating pain.

2. The use according to claim 1, characterized in that The pain includes pain that is not caused by inflammation and muscle spasm; the pain includes muscle pain, joint pain, shoulder and neck pain, pain caused by sports injuries and / or pain caused by trauma.

3. The use according to claim 1 or 2, characterized in that: The ingredients of the medicine include snake venom tripeptide, chuanxiong root extract, notopterygium root extract, safflower extract, angelica root extract, costusroot extract, centella asiatica extract, codonopsis root extract, licorice extract, ginseng extract and mugwort leaf extract.

4. The use according to claim 3, characterized in that The ingredients of the medicine also include a heat-sensing agent, oil-soluble capsicum essence, a solubilizing agent, menthol, borneol, ethanol, oil-soluble azone, propylene glycol and water.

5. The use according to claim 3 or 4, characterized in that: The amount of the snake venom tripeptide added to the medicine is 1-50 mg / kg, the amount of the Chuanxiong root extract added to the medicine is 50-400 mg / kg, the amount of the Notopterygium wilfordii extract added to the medicine is 10-600 mg / kg, the amount of the safflower extract added to the medicine is 1-600 mg / kg, the amount of the Angelica dahurica extract added to the medicine is 5-800 mg / kg, the amount of the costusroot extract added to the medicine is 10-600 mg / kg, the amount of the Centella asiatica extract added to the medicine is 100-800 mg / kg, the amount of the Codonopsis pilosula extract added to the medicine is 10-600 mg / kg, the amount of the licorice extract added to the medicine is 10-100 mg / kg, the amount of the ginseng extract added to the medicine is 10-600 mg / kg, and the amount of the Artemisia argyi extract added to the medicine is 10-600 mg / kg.

6. A drug for preventing and / or treating pain, characterized in that: The ingredients of the drug include snake venom-like tripeptide.

7. The drug according to claim 6, characterized in that The pain includes pain that is not caused by inflammation and muscle spasm; the pain includes muscle pain, joint pain, shoulder and neck pain, pain caused by sports injuries and / or pain caused by trauma.

8. The drug according to claim 6 or 7, characterized in that The ingredients of the medicine include snake venom tripeptide, chuanxiong root extract, notopterygium root extract, safflower extract, angelica root extract, costusroot extract, centella asiatica extract, codonopsis root extract, licorice extract, ginseng extract and mugwort leaf extract.

9. The drug according to claim 8, characterized in that The ingredients of the medicine also include a heat-sensing agent, oil-soluble capsicum essence, a solubilizing agent, menthol, borneol, ethanol, oil-soluble azone, propylene glycol and water.

10. The drug according to claim 8 or 9, characterized in that The amount of the snake venom tripeptide added to the medicine is 1-50 mg / kg, the amount of the Chuanxiong root extract added to the medicine is 50-400 mg / kg, the amount of the Notopterygium wilfordii extract added to the medicine is 10-600 mg / kg, the amount of the safflower extract added to the medicine is 1-600 mg / kg, the amount of the Angelica dahurica extract added to the medicine is 5-800 mg / kg, the amount of the costusroot extract added to the medicine is 10-600 mg / kg, the amount of the Centella asiatica extract added to the medicine is 100-800 mg / kg, the amount of the Codonopsis pilosula extract added to the medicine is 10-600 mg / kg, the amount of the licorice extract added to the medicine is 10-100 mg / kg, the amount of the ginseng extract added to the medicine is 10-600 mg / kg, and the amount of the Artemisia argyi extract added to the medicine is 10-600 mg / kg.

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