Application of morusin M in preparation of medicine for treating peripheral neuritis
By combining santhin M with the commonly used clinical drug adenosine cobalamin, the problem of poor treatment of peripheral neuritis in the prior art was solved, and significant enhancement of efficacy was achieved, especially in improving mechanical and cold stimulation sensitivity.
Patent Information
- Application Number
- CN202510471459.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-04-15
- Publication Date
- 2025-06-13
AI Technical Summary
The prior art has poor effect on the treatment of peripheral neuritis, and the long-term use of commonly used drugs is prone to toxic side effects, making it difficult to achieve the purpose of complete cure.
Sancinin M is used as an active ingredient, combined with other commonly used drugs for treating peripheral neuritis in clinical practice, especially in combination with adenosine-cobalamin. Through the synergistic effect of specific dosage ratios, the treatment effect is significantly enhanced.
Sancinin M significantly enhances the efficacy of drug in the treatment of peripheral neuritis, especially in combination with adenosine-cobalamin, which can significantly improve the mechanical and cold stimulation sensitivity of rats, demonstrating its significant synergistic effect in the treatment of peripheral neuritis.
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Abstract
Description
Technical Field
[0001] The present invention belongs to the field of new pharmaceutical uses, and particularly relates to the use of mulberroside M in the preparation of a medicament for treating peripheral neuritis. Background Art
[0002] Peripheral neuritis, also known as peripheral polyneuritis or multiple neuritis, is a dysfunction of the distal nerves of the limbs caused by various etiologies. The manifestations of peripheral neuritis are mainly abnormal sensory, motor, and autonomic nerve functions within the innervation range of the damaged nerves. The symptoms of peripheral neuritis include hypoesthesia, pain, numbness or pricking, formication, burning, hyperesthesia, etc. Peripheral neuritis may be multiple or single, symmetrical or asymmetrical, and is one of the most common diseases in the nervous system. At present, there are not many effective treatment methods for peripheral neuritis in clinical practice. Clinically, high-dose vitamin B complex can be used to treat peripheral neuritis caused by various reasons. Analgesics and sedatives are used for those with obvious pain. Adrenal cortical hormones, such as prednisone, dexamethasone, or hydrocortisone, can be used for those with inflammatory demyelinating lesions. However, most of these drugs have high toxic and side effects if used for a long time, and it is also difficult to achieve the goal of complete cure.
[0003] Research on traditional Chinese medicine shows that treatment methods such as oral administration of traditional Chinese medicine decoctions or patent traditional Chinese medicines, acupuncture, and massage have certain curative effects on patients with peripheral neuritis. Traditional Chinese medicine has the characteristics of syndrome differentiation and treatment, and can achieve good curative effects on patients with peripheral nerve diseases of unknown causes, and is not prone to recurrence, having certain advantages over Western medicine. However, at present, there is less research on the treatment of traditional Chinese medicine, the types of traditional Chinese medicine prescriptions and patent traditional Chinese medicines available are limited, and the common methods for treating peripheral neuritis in clinical practice of traditional Chinese medicine, such as acupuncture, electrotherapy, oral administration of traditional Chinese medicine decoctions, and external application of traditional Chinese medicine lotion, etc., have complex usage methods, are invasive, and require treatment by professionals in the hospital, so it brings many inconveniences to patients and leads to poor treatment compliance of patients.
[0004] Mulberry bark (Cortex Mori) is the dried root bark of the mulberry (Morus Alba L) plant of the Moraceae family. It is sweet, slightly bitter, and cold in nature, and belongs to the lung meridian. It has the effects of moistening the lungs and relieving asthma, promoting diuresis and reducing edema, and is mainly used for treating cough and asthma due to lung heat, edema and fullness with scanty urine, and swelling of the face, eyes and skin. Modern medicine shows that it has functions such as antiseptic and bactericidal, antioxidant, hypoglycemic, anti-tumor, anti-asthmatic and anti-inflammatory. There are literature reports that the extract of mulberry bark can prevent the decrease of cGMP and cAMP contents in the sciatic nerve of diabetic rats and Na + -K +The reduction of -ATPase activity plays a certain role in preventing and treating diabetic neuropathy (for example, see "Experimental study on the prevention and treatment of early peripheral nerve lesions in diabetic rats by Morus alba L. root bark extract", Ma Songtao et al., Journal of Chinese Medicinal Materials, Vol. 29, No. 12, December 2006, pp. 1343-1345). However, the preparation method of Morus alba L. root bark extract is not described in this literature, nor is the type of natural product monomers contained in Morus alba L. root bark extract clarified. Some studies have shown that sanggenone C, a flavonoid component with a relatively high content in Morus alba L. root bark, has obvious antihypertensive, anti-inflammatory, blood pressure-lowering, blood sugar-lowering, anti-atherosclerotic and anti-tumor effects (for example, see Wang Yi et al., "Study on the anti-tumor effects of sanggenone C in vivo and in vitro", Journal of Shihezi University (Natural Science Edition), Vol. 37, No. 4, August 2019, pp. 524-528). Sanggenol M is a phenolic component in the root bark of the mulberry plant Morus alba L., which can be extracted from Morus alba L. root bark or obtained by artificial synthesis. Existing studies have shown that sanggenol M has functions such as anti-inflammatory, asthma treatment, anti-tumor, analgesic and anti-HIV activities. However, there is currently no study on which natural product monomers in Morus alba L. root bark have a therapeutic effect on peripheral neuritis.
[0005] In the process of studying the treatment of peripheral neuritis with natural products and their extract-related monomers, the inventors of the present application first discovered that sanggenol M can be used to treat peripheral neuritis. In addition, the inventors also found that sanggenol M can significantly enhance the efficacy of other commonly used drugs for treating peripheral neuritis clinically. Summary of the Invention
[0006] The purpose of the present invention is to solve the deficiencies of the prior art, realize the development and utilization of natural products by modern research methods, and provide a new use of sanggenol M in the preparation of drugs for treating peripheral neuritis through a large number of experimental screenings.
[0007] Specifically, the present invention is achieved through the following technical solutions:
[0008] The present invention provides the use of sanggenol M in the preparation of drugs for treating peripheral neuritis.
[0009] As an optional way, in the above use, the peripheral neuritis is selected from one or more of the following: facial neuritis, diabetic peripheral neuritis, viral peripheral neuritis, peripheral neuritis caused by chemotherapeutic drugs or Guillain-Barré syndrome.
[0010] As an optional way, in the above use, the peripheral neuritis is peripheral neuritis caused by chemotherapeutic drugs.
[0011] As an optional way, in the above use, the peripheral neuritis caused by chemotherapeutic drugs is peripheral neuritis caused by platinum-based chemotherapeutic drugs.
[0012] As an alternative, in the above uses, the platinum-based chemotherapeutic drug is cisplatin, carboplatin, oxaliplatin or nedaplatin.
[0013] As an alternative, in the above uses, the symptoms of peripheral neuritis include hypoesthesia, pain, numbness or pins and needles, formication, burning, and hyperesthesia.
[0014] As an alternative, in the above uses, the use of sanggenon M as the sole active ingredient in the preparation of a drug for treating peripheral neuritis.
[0015] As an alternative, in the above uses, the drug contains the active ingredient sanggenon M and other drugs commonly used clinically for treating peripheral neuritis.
[0016] As an alternative, in the above uses, the active ingredient of the drug consists of sanggenon M and other drugs commonly used clinically for treating peripheral neuritis.
[0017] As an alternative, in the above uses, the other drugs commonly used clinically for treating peripheral neuritis are selected from one or more of the following: vitamin B1, vitamin B6, vitamin B12, mecobalamin, adenosylcobalamin or coenzyme Q10.
[0018] As an alternative, in the above uses, the other drug commonly used clinically for treating peripheral neuritis is adenosylcobalamin.
[0019] As an alternative, in the above uses, the mass ratio of sanggenon M to the other drugs commonly used clinically for treating peripheral neuritis is 5:1 to 15:1.
[0020] As an alternative, in the above uses, the mass ratio of sanggenon M to the other drugs commonly used clinically for treating peripheral neuritis is 3:2.
[0021] As an alternative, in the above uses, the drug contains the active ingredient and one or more pharmaceutically acceptable excipients.
[0022] As an alternative, in the above uses, the drug is an oral preparation or a non-oral preparation.
[0023] Preferably, the oral preparation is selected from one or more of tablets, capsules, dripping pills, granules, powders, oral films or oral liquids.
[0024] Additionally preferably, the non-oral preparation can be selected from one or more of injections, ointments, creams or suppositories.
[0025] It should be understood that within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features specifically described hereinafter (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be elaborated one by one here.
[0026] The present invention has the following beneficial effects compared with the prior art:
[0027] (1) During the research process on the treatment of peripheral neuritis with natural products and their extract-related monomers, the inventors of the present application first discovered that moracin M can be used to treat peripheral neuritis. In addition, the inventors also found that moracin M can significantly enhance the efficacy of other drugs commonly used in clinical treatment of peripheral neuritis. In particular, it was found that the combination of moracin M and cobamamide in a specific dosage ratio has a significant synergistic effect.
[0028] (2) The moracin M used in the present invention can be extracted and separated from plants such as mulberry bark containing this active ingredient. Its source is wide, the cost is low, it is economical and practical, and the safety is high. Specific Embodiments
[0029] The following further describes the present invention with reference to specific embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the scope of the present invention.
[0030] For those technical or conditions not specified in the embodiments, they shall be in accordance with the techniques or conditions described in the literature in this field or in accordance with the product instructions. For reagents or instruments without indicating the manufacturer, they are all conventional products that can be obtained through regular channels.
[0031] The experimental methods in the following examples are all conventional methods unless otherwise specified. The test materials used in the following examples are all commercially available products unless otherwise specified.
[0032] The moracin M used in the present invention can be extracted and separated from plants such as mulberry bark containing this active ingredient by using conventional extraction and purification methods in the field of natural medicine chemistry, or it can be purchased from commercially available products.
[0033] Example:
[0034] 1. Experimental Purpose
[0035] To investigate the efficacy of moracin M in treating oxaliplatin-induced peripheral neuritis.
[0036] 2. Experimental Materials
[0037] 2.1 Animals: SPF-grade female Wistar rats, weighing 160 - 180 g, purchased from Liaoning Changsheng Biotechnology Co., Ltd.
[0038] 2.2 Main drugs and reagents: Sanggenone M (purity 99.5%) and cobamamide (purity 99.9%) were purchased from Shenyang Sandu Medical Technology Co., Ltd. Oxaliplatin (trade name: Eloxatin) injection was purchased from Jiangsu Hengrui Medicine Co., Ltd.
[0039] 3. Experimental methods
[0040] 3.1. Grouping of experimental animals, model establishment and dosing regimen
[0041] After female Wistar rats were adaptively fed for one week, they were divided into 7 groups according to the random numbers generated by SPSS, with 8 rats in each group: blank group, model group, sanggenin M group, sanggenone C group, cobamamide group, sanggenin M + cobamamide group, sanggenone C + cobamamide group.
[0042] Oxaliplatin was diluted with 5% glucose to 1 mg / mL. Rats in the model group, sanggenin M group, cobamamide group, and sanggenin M + cobamamide group were intraperitoneally injected with oxaliplatin at 4 mg / kg, and the blank group was injected with 0.9% normal saline. The injection was given twice a week for 2 consecutive weeks (equivalent to injecting on the 1st, 2nd, 8th, and 9th days respectively). On the 7th day after the start of modeling, a mechanical sensitivity experiment was conducted. If the mechanical stimulus sensitivity of the experimental animals in the model group was significantly reduced compared with that of the blank group, it indicated that the modeling was successful.
[0043] The grouping and dosing of this experiment are as follows:
[0044] (1) Blank group;
[0045] (2) Model group;
[0046] (3) Sanggenin M (3 mg / kg) group;
[0047] (4) Sanggenone C (3 mg / kg) group;
[0048] (5) Cobamamide (2 mg / kg) group;
[0049] (6) Sanggenin M (3 mg / kg) + cobamamide (2 mg / kg) group;
[0050] (7) Sanggenone C (3 mg / kg) + cobamamide (2 mg / kg) group.
[0051] Medication started on day 0. Rats in the blank group and the model group were intragastrically administered 0.9% normal saline, and the remaining treatment groups were intragastrically administered according to the body weight of the rats once a day for 14 consecutive days.
[0052] 3.2. Evaluation indicators
[0053] 3.2.1 Mechanical sensitivity experiment
[0054] The test rats were placed on a metal net with 1 cm × 1 cm small squares at the bottom, and surrounded by transparent plexiglass on all sides to prevent the rats from moving around randomly. The rats were allowed to adapt in a quiet environment for 15 min, waiting for their exploratory and grooming behaviors to basically disappear. The Up and Down method was used for testing. Eight Von Frey filaments with different gram weights (purchased from North Coast Medical, Inc., USA) were used for increasing and decreasing tests, which were 0.41 g, 0.70 g, 1.20 g, 2.04 g, 3.63 g, 5.50 g, 8.51 g, and 15.14 g respectively. First, the 2.04 g filament was used for the initial test. The filament was used to stimulate the skin of the right plantar surface of the rat, and the stimulation duration each time was 6 - 8 s. According to whether the rat withdrew its foot, its positivity or negativity was judged. When the rat withdrew its foot, the gram weight was decreased, and vice versa. A total of 9 tests were conducted, and the relevant results were recorded. Calculations were made using a conventional formula, and finally the 50% mechanical pain threshold value (g) was obtained, which was detected once a week.
[0055] 3.2.2 Cold Stimulation Sensitivity Experiment
[0056] The same method as in the above "3.2.1" section was adopted to let the rats adapt in a quiet environment. Subsequently, 50 μL of acetone was sprayed onto the skin of the right paw plantar surface of the rats using a 1 mL syringe, and each rat was sprayed 3 times. The start time of spraying was set as 0 seconds, and a total of 40 seconds was counted. The number of times the rats withdrew their feet within 40 seconds was calculated, which was detected once a week.
[0057] 3.2.3 Statistical Analysis Method
[0058] The results were analyzed using SPSS 23.0 statistical software, and the data were expressed as mean ± standard deviation. One-way ANOVA was used for comparison among multiple groups, and the t-test was used for comparison between two groups. p < 0.05 indicated that the difference was statistically significant.
[0059] 4. Experimental Results
[0060] The results of the mechanical sensitivity experiment in rats are shown in Table 1. Compared with the model group, the 50% mechanical pain threshold values (g) of the rats in the blank group were significantly different on the 7th and 14th days (**p < 0.01, ***p < 0.001). Compared with the model group, the 50% mechanical pain threshold values (g) of the rats in the sanggenin M group were significantly different on the 7th and 14th days (*p < 0.05, **p < 0.01), indicating that sanggenin M has the effect of improving mechanical sensitivity in model rats. At the experimental dose, cobamamide also had a certain effect on improving the 50% mechanical pain threshold value (g) of rats, but the difference compared with the model group was not significant. However, it is worth noting that after combining sanggenin M and cobamamide, a significant synergistic effect was produced between them. Compared with the model group, the 50% mechanical pain threshold values (g) of the rats in the combined group were extremely significantly different on the 7th and 14th days (**p < 0.01, ***p < 0.001). However, it can also be seen from the results in Table 1 that, as an extract from the same cortex mori, sanggenone C basically had no effect on improving mechanical sensitivity in model rats, indicating that the effect of sanggenin M in treating oxaliplatin-induced peripheral neuritis may be somewhat related to its chemical structure.
[0061] Table 1: Results of the mechanical sensitivity experiment in rats (50% mechanical pain threshold value, unit: g)
[0062]
[0063] Note: Compared with the model group, *p < 0.05, **p < 0.01, ***p < 0.001.
[0064] The results of the cold stimulus sensitivity experiment in rats are shown in Table 2. Compared with the model group, the number of foot withdrawals of the rats in the blank group was significantly different on the 7th and 14th days (*p < 0.05, **p < 0.01). Compared with the model group, the number of foot withdrawals of the rats in the sanggenin M group was significantly different on the 7th and 14th days (*p < 0.05), indicating that sanggenin M has the effect of improving cold stimulus sensitivity in model rats. At the experimental dose, cobamamide also had a certain effect on improving the number of foot withdrawals of rats, but the difference compared with the model group was not significant. However, it is worth noting that after combining sanggenin M and cobamamide, a significant synergistic effect was produced between them. Compared with the model group, the number of foot withdrawals of the rats in the combined group was extremely significantly different on the 7th and 14th days (*p < 0.05, **p < 0.01). However, it can also be seen from the results in Table 2 that, as an extract from the same cortex mori, sanggenone C basically had no effect on improving cold stimulus sensitivity in model rats, indicating that the effect of sanggenin M in treating oxaliplatin-induced peripheral neuritis may be somewhat related to its chemical structure.
[0065] Table 2: Results of cold stimulation sensitivity experiment in rats (number of foot withdrawals, unit: times)
[0066]
[0067] Note: Compared with the model group, *p < 0.05, **p < 0.01.
[0068] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalent technologies, the present invention is also intended to include these modifications and variations.
Claims
1. Use of sansinsu M in preparing medicine for treating peripheral neuritis.
2. The use according to claim 1, characterized in that: The peripheral neuritis is selected from one or more of the following: facial neuritis, diabetic peripheral neuritis, viral peripheral neuritis, peripheral neuritis caused by chemotherapy drugs or Guillain-Barré syndrome.
3. The use according to claim 2, characterized in that: The peripheral neuritis caused by the chemotherapy drugs is peripheral neuritis caused by platinum chemotherapy drugs.
4. The use according to claim 1, characterized in that: The symptoms of peripheral neuritis include decreased sensation, pain, numbness or tingling, tingling, burning, hyperesthesia.
5. The use according to claim 1, characterized in that: Use of sancinol M as the sole active ingredient in preparing medicines for treating peripheral neuritis.
6. The use according to claim 1, characterized in that: The medicine comprises an active ingredient, sansinsu M, and other medicines commonly used in clinical practice for treating peripheral neuritis.
7. The use according to claim 6, characterized in that: The other commonly used drugs for treating peripheral neuritis in clinical practice are selected from one or more of the following: vitamin B1, vitamin B6, vitamin B12, methylcobalamin, adenosylcobalamin or coenzyme Q10.
8. The use according to claim 6, characterized in that: The mass ratio of the sansinsu M to the other clinically commonly used drugs for treating peripheral neuritis is 5:1 to 15:
1.
9. The use according to claim 1, characterized in that: The medicament comprises an active ingredient and one or more pharmaceutically acceptable excipients.
10. The use according to claim 1, characterized in that: The medicine is an oral preparation or a non-oral preparation, the oral preparation is selected from one or more of tablets, capsules, pills, granules, powders, oral films or oral liquids, and the non-oral preparation can be selected from one or more of injections, ointments, creams or suppositories.