CN114306359A - Analgesic application of pulsatilla chinensis or extract thereof - Google Patents
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Abstract
The invention provides application of pulsatilla saponin B5 or pharmaceutically acceptable salts, co-crystals, stereoisomers, prodrugs, solvates and metabolites thereof in preparation of drugs for preventing and/or treating pain, which can significantly relieve the severity of neuropathic pain, for example, improve the mechanical pain threshold caused by von Frey nylon fiber vertical stimulation or the cold pain threshold caused by acetone stimulation of a spinal nerve ligation model, and the like.
Description
Technical Field
The invention relates to the technical field of biological medicines, in particular to application of pulsatilla saponin B5 in preparation of a medicine for treating pain.
Background
Neuropathic pain is the top killer of chronic pain due to its long course of disease, poor therapeutic effect, and severe impact on the quality of life of patients. The disease is high in morbidity, complex in pathogenesis and lack of an effective treatment method, at present, the first-line analgesic drug therapy mainly takes drug treatment as main treatment, the common first-line analgesic drug therapy comprises tricyclic antidepressant (TCA), serotonin-norepinephrine reuptake inhibitor (SNRI), gabapentin and the like, the main effects of the drugs are not analgesia, and only the drug effect of analgesia is found later, so the drugs are listed as auxiliary analgesic drugs.
In the research of treating neuropathic pain, a plurality of traditional Chinese medicines are developed around the analgesic effect, such as the application of echinacoside in preparing medicines for treating neuropathic pain, wherein the publication number is CN 112494505A; also, as disclosed in publication No. CN107137413A, entitled pasqueflower saponin B4, in the preparation of a drug for treating pain, it was found that pasqueflower saponin B4 has a good pain-relieving effect on a mouse writhing model caused by acetic acid, a thermal radiating pain model, a formalin-induced mouse pain model and a rat pain model. However, the structures of the pulsatilla saponin B4 and the pulsatilla saponin B5 are greatly different, the aglycone mother nucleus is different, the lupane saponin is used as the lupane saponin, the oleanane saponin is used as the oleanane saponin, a classical neuropathic pain (spinal nerve ligation) model is adopted, and the analgesic molecular action mechanism of the pulsatilla saponin B5 is disclosed through transcriptome sequencing.
The pulsatilla saponin B5 is one of the main active ingredients of the traditional Chinese medicine pulsatilla, belongs to saponin ingredients, and has pharmacological actions of resisting inflammation, resisting virus, resisting tumor, resisting oxidation, resisting histamine, enhancing human immunity and the like according to modern pharmacological research. Most of the previous reported researches are carried out around a lot of activities of pulsatilla saponin B4, and the current researches on the activity of pulsatilla saponin B5 are less, such as the application of the pulsatilla saponin B5 in preparing a medicament for preventing and/or treating enterovirus infection, which is disclosed as publication No. CN108030785A, and the name of the pulsatilla saponin B5 proves that the pulsatilla saponin B5 has strong antiviral activity, but the pulsatilla saponin B5 has not been reported in the aspect of analgesia at present.
Disclosure of Invention
The invention provides a new application of pulsatilla saponin B5, namely preventing and/or treating pain. The embodiment proves that the pulsatillae saponin B5 can significantly relieve the severity of neuropathic pain, for example, the mechanical pain threshold caused by von Frey nylon cellosilk vertical stimulation or the cold pain threshold caused by acetone stimulation of the spinal nerve ligation model can be improved, and the effect is more excellent than that of the conventional pregabalin. The analgesic mechanism of pulsatilla saponin B5 is related to inhibition of nerve pathways such as chemokine signals, and can be used for preparing medicines for treating neuropathic pain. And the rat has good state and no obvious side effect while effectively relieving the pain.
In a first aspect of the present invention, there is provided use of pulsatillae radix or an extract thereof for preparing a medicament for preventing and/or treating pain.
The pulsatilla chinensis is a pulsatilla chinensis plant or a dried root thereof.
The pulsatilla chinensis extract comprises pulsatilla chinensis saponin, preferably oleanane type saponin.
In one embodiment of the present invention, the pulsatilla chinensis bunge extract comprises pulsatilla chinensis bunge saponin B5, which has the following structural formula:
the pain includes neuropathic pain. Neuropathic Pain (NP) is a chronic Pain that manifests as clinical symptoms such as burning, stabbing, tearing and the like, and can also cause negative emotions such as depression and anxiety in patients. The international society for pain research defines "pain stimulated or caused by primary injuries and dysfunctions of the nervous system".
Preferably, the neuropathic pain includes peripheral sensitization, central sensitization and/or central descending inhibitory regulation change, and the like, and is particularly induced by diseases such as chemotherapy, spinal cord injury, mitochondrial dysfunction and/or diabetes. Preferably peripheral sensitized neuropathic pain.
In one embodiment of the invention, the pain comprises mechanical pain or cold pain.
Preferably, said preventing and/or treating pain comprises increasing the pain threshold.
Preferably, the preventing and/or treating pain comprises applying an effective amount of pulsatillae radix or an extract thereof to the individual.
Preferably, the medicine comprises pulsatilla chinensis or an extract thereof and pharmaceutically acceptable auxiliary materials.
In a second aspect of the invention, there is provided the use of an oleanane-type saponin or a pharmaceutically acceptable salt, co-crystal, stereoisomer, prodrug, solvate, metabolite thereof in the manufacture of a medicament for the prevention and/or treatment of pain.
The preventing and/or treating pain comprises applying an effective amount of oleanane-type saponin or pharmaceutically acceptable salt, co-crystal, stereoisomer, prodrug, solvate, metabolite thereof to the individual.
The medicine comprises oleanane type saponin or pharmaceutically acceptable salt, eutectic, stereoisomer, prodrug, solvate, metabolite and pharmaceutically acceptable auxiliary materials thereof.
In a third aspect of the invention, the application of the pulsatilla saponin B5 or the pharmaceutically acceptable salt, eutectic crystal, stereoisomer, prodrug, solvate and metabolite thereof in preparing the medicine for preventing and/or treating pain is provided.
The pain includes neuropathic pain.
The pain includes mechanical pain or cold pain.
The prevention and/or treatment of pain comprises an increase in pain threshold.
The preventing and/or treating pain comprises applying an effective amount of pasqueflower saponin B5 or its pharmaceutically acceptable salt, cocrystal, stereoisomer, prodrug, solvate, metabolite to individual.
The medicine comprises anemoside B5 or pharmaceutically acceptable salt, eutectic, stereoisomer, prodrug, solvate, metabolite and pharmaceutically acceptable auxiliary materials thereof.
Preferably, the medicine also comprises other pulsatilla chinensis extract except pulsatilla chinensis saponin B5.
The anemonin B5 can be obtained by artificial synthesis or extraction from radix Pulsatillae.
In a fourth aspect of the invention, the invention provides an application of pulsatillae radix or its extract in regulating genes or its encoded proteins, wherein the genes or its encoded proteins include one or a combination of two or more of Slc24a1, Gch1, RT1-A2, Cd74, Car13, Grk1, Rgs9, Car3, C7, Cacna1f, Tph1, A2m, Gnat2, Ddc, LOC100911545, Lama2, Cngb1, RT1-Ba, Cacna2d4, Pde6g, RT1-Da, Adrb1, Gngt1, Guca1b or Guca1 a.
In a fifth aspect of the present invention, there is provided an oleanane-type saponin or a pharmaceutically acceptable salt, a co-crystal, a stereoisomer, a prodrug, a solvate, a metabolite thereof, or an application of pulsatilla saponin B5 or a pharmaceutically acceptable salt, a co-crystal, a stereoisomer, a prodrug, a solvate, a metabolite thereof in regulating genes or encoded proteins thereof, wherein the genes or encoded proteins thereof include one or more of Slc24a1, Gch1, RT1-A2, Cd74, Car13, Grk1, Rgs9, Car3, C7, Cacna1f, Tph1, A2m, Gnat2, d 154dc 100915, Lama2, Cngb 9, RT1-Ba, Cacna2d4, Pde6g, RT1-Da, Adrb1, gca 1, Guca1 or a combination of more than two of them B.
In a sixth aspect of the present invention, there is provided a use of a gene or a protein encoded by the gene as a target for preventing and/or treating pain, wherein the gene or the protein encoded by the gene comprises one or a combination of two or more of Slc24a1, Gch1, RT1-A2, Cd74, Car13, Grk1, Rgs9, Car3, C7, Cacna1f, Tph1, A2m, Gnat2, Ddc, LOC100911545, Lama2, Cngb1, RT1-Ba, Cacna2d4, Pde6g, RT1-Da, Adrb1, Gngt1, Guca1b, and Guca1 a.
In a seventh aspect of the invention, the invention provides an application of a reagent for regulating genes or encoding proteins thereof in preparing a medicament for preventing and/or treating pain, wherein the genes or the encoding proteins thereof comprise one or a combination of two or more of Slc24a1, Gch1, RT1-A2, Cd74, Car13, Grk1, Rgs9, Car3, C7, Cacnna 1f, Tph1, A2m, Gnat2, Ddc, LOC 100915, Lama2, Cngb1, RT1-Ba, Cacnna 2d4, Pde6g, RT1-Da, Adrb1, Gnggt 1, Guca1b or Guca1 a.
Preferably, the prevention and/or treatment of pain comprises regulating the expression level of a gene or the concentration of a protein encoded by the gene.
Preferably, the modulation comprises up-regulation or down-regulation. Wherein, the up-regulation can be the over-expression of the corresponding gene or the increase of the concentration of the corresponding protein. Downregulation may be a knock-out or a knock-down of the corresponding gene or the addition of an inhibitor of the corresponding protein. Further, agents that regulate a gene or its encoded protein may be adapted to the desired agent according to the method of up-regulating or down-regulating a gene or its encoded protein.
The agent for regulating the gene or the protein encoded by the gene comprises pulsatilla chinensis or an extract thereof.
The agent for regulating the gene or the encoded protein thereof comprises an oleanane-type saponin or a pharmaceutically acceptable salt, a cocrystal, a stereoisomer, a prodrug, a solvate and a metabolite thereof, or the pulsatilla saponin B5 or a pharmaceutically acceptable salt, a cocrystal, a stereoisomer, a prodrug, a solvate and a metabolite thereof.
The medicine comprises a reagent for regulating and controlling genes or coding proteins thereof and pharmaceutically acceptable auxiliary materials.
In an eighth aspect of the present invention, there is provided a method for preventing and/or treating pain, the method comprising administering an effective amount of pulsatillae radix or an extract thereof to an individual, or administering an effective amount of oleanane-type saponin or a pharmaceutically acceptable salt, cocrystal, stereoisomer, prodrug, solvate, metabolite thereof, or pulsatillae radix saponin B5 or a pharmaceutically acceptable salt, cocrystal, stereoisomer, prodrug, solvate, metabolite thereof to an individual.
In a ninth aspect of the invention, there is provided a method of preventing and/or treating pain, the method comprising modulating a gene or protein encoding the same.
The pulsatillae radix of the present invention includes but is not limited to pulsatillae radix, pulsatilla pulverata or pulsatilla, i.e., a plant belonging to ranunculus (Ranunculaceae).
The "extract of pulsatillae radix" as described in the present invention includes, but is not limited to, ranunculin, deoxypodophyllotoxin and 3-oxo- α -L-rhamnopyranosyl (1 → 2) - [ β -D-glucopyranosyl (1 → 4) ] - α -L-arabinopyranoside, etc. It can be extracted by conventional methods in the art, such as by alcohol extraction.
"prevention" as used herein means the practice of preventing or delaying the onset of a disease or disorder or condition in the body.
"treating" as used herein means slowing, interrupting, arresting, controlling, stopping, alleviating, or reversing the progression or severity of one sign, symptom, disorder, condition, or disease after the disease has begun to develop, but does not necessarily involve complete elimination of all disease-related signs, symptoms, conditions, or disorders.
An "effective amount" as referred to herein, refers to an amount or dose of a drug of the present invention which provides the desired treatment or prevention after administration to an individual or organ in single or multiple doses.
An "individual" of the invention can be a human or non-human mammal, which can be a wild animal, a zoo animal, an economic animal, a pet, a laboratory animal, and the like. Preferably, the non-human mammal includes, but is not limited to, a pig, a cow, a sheep, a horse, a donkey, a fox, a racoon dog, a mink, a camel, a dog, a cat, a rabbit, a mouse (e.g., rat, mouse, guinea pig, hamster, gerbil, dragon cat, squirrel), or a monkey, and the like.
The term "pharmaceutically acceptable" as used herein means that the biological activity and properties of the active substance are neither significantly stimulating the organism nor inhibiting the administered product.
The term "pharmaceutically acceptable salt" as used herein refers to a salt prepared from a pharmaceutically acceptable non-toxic acid or base, wherein the acid or base includes inorganic or organic acids or bases. The inorganic acid is selected from hydrochloric acid, hydrobromic acid, phosphoric acid, hydroiodic acid or sulfuric acid. The inorganic alkali is selected from calcium, magnesium, lithium, sodium, zinc, aluminum or potassium. The organic acid is selected from formic acid, glycolic acid, propionic acid, acetic acid, succinic acid, methanesulfonic acid, ethanesulfonic acid, maleic acid, glutamic acid, benzoic acid, stearic acid, alginic acid, benzenesulfonic acid, glucuronic acid, pamoic acid or galacturonic acid. The organic base is selected from diethanolamine, choline, procaine, lysine or 1, 2-ethylenediamine.
The "co-crystal" of the present invention refers to a crystal in which the compound of the present invention (for example, oleanane-type saponin or pulsatilla saponin B5) is bonded to other physiologically acceptable acid, base, or nonionic compound by non-covalent bond such as hydrogen bond, van der waals force, pi-pi stacking effect, or halogen bond.
"stereoisomers" as used herein include enantiomeric, diastereomeric and geometric forms.
The prodrug is a compound which is obtained by modifying a chemical structure of a drug, has no or less activity in vitro or at a non-specific target position, and can release an active drug (such as the oleanane-type saponin or the pulsatilla saponin B5) through enzymatic or non-enzymatic conversion in vivo to exert the drug effect.
The "solvate" of the present invention refers to a physical association of a compound of the present invention (e.g., oleanane-type saponin or pulsatilla saponin B5) with one or more solvent molecules. The physical bonding includes various degrees of ionic and covalent bonding, including hydrogen bonding. In some cases, the solvate may be isolated, for example, when one or more solvent molecules are incorporated into the crystal lattice of the crystalline solid. Solvates include solution phase and isolatable solvates. Representative solvates include ethanolates, methanolates, and the like.
The "metabolite" of the present invention refers to a product obtained by chemically degrading the compound of the present invention (e.g., oleanane-type saponin or pulsatilla saponin B5) under physiological conditions in vivo.
The "pharmaceutically acceptable adjuvant" according to the present invention includes, but is not limited to, one or more of carriers, excipients, diluents, wetting agents, fillers, binders, lubricants, disintegrants, antioxidants, buffers, suspending agents, solubilizers, thickeners, stabilizers, flavoring agents, preservatives, and the like.
The agents of the invention may be administered by any suitable route of administration, for example, gastrointestinal (e.g., oral) or parenteral (e.g., intravenous, intramuscular, subcutaneous, intradermal, intraorgan, intranasal, intraocular, instillation, intracerebral, intrathecal, transdermal, intrarectal, etc.) routes. In one embodiment of the invention, the route of administration is oral or injectable.
The pharmaceutical agent of the present invention may be in any suitable dosage form, such as a gastrointestinal administration form or a parenteral administration form, and preferably includes, but is not limited to, tablets, pills, powders, granules, capsules, lozenges, syrups, liquids, emulsions, microemulsions, suspensions, injections, sprays, aerosols, dusts, lotions, ointments, plasters, pastes, patches, eye drops, nasal drops, sublingual tablets, suppositories, aerosols, effervescent tablets, drop pills, gels, and the like.
The dose of the drug of the present invention for single application is limited to a dose that does not cause central inhibition.
Various dosage forms of the medicament of the invention can be prepared according to conventional production methods in the pharmaceutical field.
The drug of the present invention may contain 0.01 to 99.5% (specifically, 0.01%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, 99.5%) by weight of the compound (e.g., oleanane-type saponin or pulsatilla saponin B5) or a pharmaceutically acceptable salt, stereoisomer, prodrug, solvate, or metabolite thereof.
The medicament can be human medicament or veterinary medicament.
The terms "comprises" and "comprising" as used herein are intended to be open-ended terms that specify the presence of the stated elements or steps, and not substantially affect the presence of other stated elements or steps.
All combinations of items described herein as "and/or" including "are to be understood as meaning that each combination has been individually listed herein. For example, "A and/or B" includes "A", "A and B", and "B". As another example, "A, B and/or C" includes "A", "B", "C", "A and B", "A and C", "B and C", and "A and B and C".
Drawings
Embodiments of the invention are described in detail below with reference to the attached drawing figures, wherein:
FIG. 1: after administration, each group of rats had 50% withdrawal threshold test results.
FIG. 2: after administration, the number of foot contraction or licking reactions of rats in each group to cold pain caused by acetone stimulation was compared.
FIG. 3A: SNL and Con groups differentially expressed genes.
FIG. 3B: SNL and B5 group differential expression gene analysis results.
FIG. 4A: and (4) carrying out KEGG enrichment analysis on the differential expression genes to obtain signal paths mainly regulated and controlled by the differential expression genes of the SNL group and the Con group.
FIG. 4B: and carrying out KEGG enrichment analysis on the differential expression genes to obtain signal paths mainly regulated and controlled by the SNL and B5 differential expression genes.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only some embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Experimental animals used in the examples: SD rat, male, 210-: SCXK (Jing) 2019-. The animals were housed in the institute of Chinese medicine, academy of traditional Chinese medicine.
The Spinal Nerve Ligation (SNL) model used in the examples is a well-known ideal neuropathic Pain model, simulates the disease state of Neuropathic Pain (NP), and examines the analgesic effect characteristics of pulsatilla saponin B5 on NP.
The pregabalin capsules used in the examples were purchased from the pfeiffer pharmaceuticals, ltd, national drug standard J20100102.
Example 1
First, experiment method
1. Construction of SNL rat model
After anesthetizing the rats, the back skin was shaved to expose the skin. The skin is cut perpendicular to the line between the spine and the anterior superior iliac spine. The tissue was dissected microscopically and the left L6 transverse process of the vertebral body was found, exposing the L4, L5 spinal nerves. After separating the spinal nerves L4 and L5, the spinal nerves L5 were ligated with surgical suture.
2. Experimental medicine and reagent
2% sodium pentobarbital; pulsatillae saponin B5; pregabalin capsules.
3. Animal grouping and administration
Negative control group (Con), model group (SNL), anemonin B5 group (B5 for short), and Pregabalin Group (PGB).
10 rats in each group recovered for 3 days after the molding was finished, and then the administration was continued for 14 days, wherein B5 was intraperitoneally injected (dose: 4.15 mg/kg), PGB was intragastrically administered (dose: 22.5 mg/kg), and Con and SNL groups of rats were intragastrically administered with an equal volume of physiological saline.
Tissue material selection: after the dosing cycle was completed, the rats were anesthetized and the hippocampal tissue of the brain was removed. Washed with PBS and stored in a cryopreservation tube at-80 ℃ for transcriptome sequencing.
4. Method for detecting mechanical pain
The mechanical pain threshold of the rat left foot L5 reflex zone was measured using von Frey nylon fiber (stimulation force measured in the range of 0.008g-300 g). Rats were placed in individually closed cages and the environment was kept quiet. Rats were stimulated vertically with von Frey nylon fiber to the left volar skin. The stimulation strength is adjusted by changing von Frey nylon fiber. The rat paw withdrawal response was positive within 5 seconds until the fiber was bent. The 50% withdrawal response threshold was calculated according to the up-and-down method. The detection time points of the 50% foot shrinkage threshold are set at 1h, 1.5h, 2h, 3h, 5h and 7h after the last administration is finished.
5. Cold pain threshold detection method
The cold pain threshold was measured using acetone stimulation. Rats were placed in individual closed cages and the environment was kept quiet. The left dorsum pedis skin of the rats was given 20uL of acetone to stimulate the rats to either contract or lick the feet. The number of reflections from the paw withdrawal or licking within 30s was recorded. The cold pain threshold detection time point is set at the 2h after the last administration.
6. Screening for differentially expressed genes
Based on transcriptome data, we generally screened differentially expressed genes using a log2 (fold change) method and performed hierarchical clustering using an R heat map package.
7. Pathway enrichment analysis
The screened differentially expressed genes were analyzed for Cellular Components (CC), Molecular Function (MF), Biological Processes (BP) by GO database and pathway analysis by KEGG database. The related pathway of B5 for exerting analgesic effect is obtained by enrichment analysis.
Second, experimental results
1. B5 remarkably raises mechanical pain threshold of SNL rats
The results are shown in FIG. 1, and the mechanical pain threshold of SNL group is obviously reduced compared with Con group at the end of administration (1 h, 1.5h, 2h, 3h and 5 h) ((P<0.05). In the SNL group, both the B5 group and pregabalin group increased the mechanical pain threshold of the SNL rats to a different extent than the administration group. After 2h of administration, the B5 group had the most significant efficacy in increasing the mechanical pain threshold of SNL rats (P<0.05) and is significantly better than the pregabalin group (P<0.05）。
2. B5 raised cold pain threshold of SNL rats
The results are shown in fig. 2, at 2h after the end of the administration, the cold pain threshold of the SNL group is obviously reduced compared with the Con group, namely, the number of cold pain foot contraction or foot licking reactions of the animals caused by the stimulation of acetone is increased (the frequency of the cold pain foot contraction or foot licking reactions of the animals is increased: (the frequency of the cold pain foot contraction or foot licking reactions caused by the stimulation of acetone is increased)P<0.01). Compared with the administration group, the B5 group and the pregabalin group both increase the cold pain threshold of the SNL rats, namely, the number of times of cold pain foot contraction or licking response of the animals to acetone stimulation is obviously reduced, wherein the increase of the cold pain threshold of the B5 group rats is most obvious (the B5 group rats are the most obvious in the cases of cold pain of the animals in the cases of cold pain and cold pain of the animals in the cases of cold pain and cold pain of the animals in the other animals in the cases of cold pain, the cold pain of the animals in the cold pain of the animals in the B5 group of the animals in the other cases of the cold pain of the animals in the groups (the animals in the groups of the animals in the groups of the animals in the groups of the animals in the groups of the animals in the groups in theP<0.05)。
3. Differentially expressed genes
The SNL and Con groups were subjected to differential expression gene analysis to obtain 323 differential expression genes. There were 49 up-regulated genes and 274 down-regulated genes (see FIG. 3A). SNL shared 829 differentially expressed genes with 692 of these genes up-regulated and 137 of these genes down-regulated (see fig. 3B) with group B5.
4. Pathway enrichment analysis
KEGG enrichment analysis is carried out according to the differential expression genes, and signal paths mainly regulated by the differential expression genes between the SNL group and the Con group (see figure 4A) and between the SNL group and the B5 group (see figure 4B) are obtained. The common signaling pathways enriched in SNL and Con groups, B5 include Phototranducation (Phototransduction), Nitrogen metabolism (Nitrogen metabolism), Graft-cover-host disease (Graft versus host disease), Folate biosynthesis (Folate biosynthesis), allografting rejection, autoimmunity disease (Autoimmune thyroid disease), Type I diabetes mellitus (Type I diabetes), Viral mycocardias (Viral myocarditis), Cocaine adsorption (Cocaine addiction), Antigen processing and presentation (Antigen processing and presentation), composite and conjugation models (pathway), and diagnosis (Dilated cardiomyopathy). The common signal pathways contain 25 identical differentially expressed genes (Slc 24a1 gene, Gch1 gene, RT1-A2 gene, Cd74 gene, Car13 gene, Grk1 gene, Rgs9 gene, Car3 gene, C7 gene, Cacna1f gene, Tph1 gene, A2m gene, Gnat2 gene, Ddc gene, LOC100911545 gene, Lama2 gene, Cngb1 gene, RT1-Ba gene, Cacna2d4 gene, Pde6g gene, RT1-Da gene, Adrb1 gene, Gnggt 1 gene, Guca1b gene, Guca1a gene). It was suggested that pulsatillae saponin B5 could play a role in relieving neuropathic pain by regulating the above 25 genes.
The preferred embodiments of the present invention have been described in detail, however, the present invention is not limited to the specific details of the above embodiments, and various simple modifications may be made to the technical solution of the present invention within the technical idea of the present invention, and these simple modifications are within the protective scope of the present invention.
It should be noted that the various technical features described in the above embodiments can be combined in any suitable manner without contradiction, and the invention is not described in any way for the possible combinations in order to avoid unnecessary repetition.
Claims (10)
1. The application of the pulsatilla saponin B5 or pharmaceutically acceptable salts, cocrystals, stereoisomers, prodrugs, solvates and metabolites thereof in preparing medicines for preventing and/or treating pain.
2. The use of claim 1, wherein the pain comprises neuropathic pain.
3. The use according to claim 1, wherein the pain comprises mechanical pain or cold pain.
4. The use according to claim 1, wherein the prevention and/or treatment of pain comprises an increase in pain threshold.
5. The use according to claim 1, wherein the prevention and/or treatment of pain comprises administering an effective amount of pasqueflower saponin B5 or a pharmaceutically acceptable salt, co-crystal, stereoisomer, prodrug, solvate, metabolite thereof to an individual.
6. The use according to any one of claims 1 to 5, wherein the medicament comprises pulsatillae saponin B5 or a pharmaceutically acceptable salt, cocrystal, stereoisomer, prodrug, solvate, metabolite thereof, and a pharmaceutically acceptable excipient.
7. The application of a gene or a protein coded by the gene as a target for preventing and/or treating pain is characterized in that the gene or the protein coded by the gene comprises one or a combination of two or more of Slc24a1, Gch1, RT1-A2, Cd74, Car13, Grk1, Rgs9, Car3, C7, Cacna1f, Tph1, A2m, Gat 2, Ddc, LOC 100154915, Lama2, Cngb1, RT1-Ba, Cacnna 2d4, Pde6g, RT1-Da, Adrb1, Gnggt 1, Guca1b or Guca1 a.
8. The application of a reagent for regulating genes or encoding proteins thereof in preparing a medicament for preventing and/or treating pain is characterized in that the genes or encoding proteins thereof comprise one or the combination of two or more of Slc24a1, Gch1, RT1-A2, Cd74, Car13, Grk1, Rgs9, Car3, C7, Cacnna 1f, Tph1, A2m, Gnat2, Ddc, LOC 100915, Lama2, Cngb1, RT1-Ba, Cacnna 2d4, Pde6g, RT1-Da, Adrb1, Gnggt 1, Guca1b or Guca1 a.
9. The use according to claim 7 or 8, wherein the prevention and/or treatment of pain comprises regulating the expression level of a gene or the concentration of a protein encoded by the gene.
10. The use according to claim 8, wherein the agent regulating the gene or the protein encoded thereby comprises pasqueoside B5 or a pharmaceutically acceptable salt, co-crystal, stereoisomer, prodrug, solvate, metabolite thereof.
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| CN107137413A (en) * | 2017-06-21 | 2017-09-08 | 苏州大学 | Pulchinenoside B4Application in the medicine for preparing treatment pain |
| CN110200981A (en) * | 2019-06-06 | 2019-09-06 | 中国药科大学 | The medical usage and its pharmaceutical composition of pentacyclic triterpene saponin |
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| CN107137413A (en) * | 2017-06-21 | 2017-09-08 | 苏州大学 | Pulchinenoside B4Application in the medicine for preparing treatment pain |
| CN110200981A (en) * | 2019-06-06 | 2019-09-06 | 中国药科大学 | The medical usage and its pharmaceutical composition of pentacyclic triterpene saponin |
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| SU CHEN等: "Analgesic Effects of Triterpenoid", 《FRONTIERS IN PHARMACOLOGY》 * |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114681474A (en) * | 2022-05-10 | 2022-07-01 | 广西林洋药业有限公司 | Composition with detumescence and itching relieving effects |
| CN114681474B (en) * | 2022-05-10 | 2023-11-24 | 广西林洋药业有限公司 | Composition with detumescence and antipruritic effects |
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| CN114306359B (en) | 2022-06-17 |
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