CN115381853A - Use of molybdenum carbide in preparation of medicament for treating fibromyalgia syndrome and/or depression - Google Patents

Use of molybdenum carbide in preparation of medicament for treating fibromyalgia syndrome and/or depression Download PDF

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Publication number
CN115381853A
CN115381853A CN202210868657.4A CN202210868657A CN115381853A CN 115381853 A CN115381853 A CN 115381853A CN 202210868657 A CN202210868657 A CN 202210868657A CN 115381853 A CN115381853 A CN 115381853A
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molybdenum carbide
medicament
depression
pain
fibromyalgia syndrome
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张定坤
蒋玲
熊怡霄
李涛
龚萌
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West China Hospital of Sichuan University
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West China Hospital of Sichuan University
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/22—Anxiolytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

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Abstract

The invention provides a molybdenum carbide nanoenzyme which has an effective relieving effect on chronic pain and an improving effect on depression symptoms, and provides a new choice for clinical treatment of fibromyalgia syndrome and/or depression.

Description

Use of molybdenum carbide in preparation of medicament for treating fibromyalgia syndrome and/or depression
Technical Field
The invention belongs to the field of biomedicine, and particularly relates to application of molybdenum carbide in preparation of a medicament for treating fibromyalgia syndrome and/or depression.
Background
Fibromyalgia syndrome (FMS) is a clinical syndrome characterized by chronic widespread pain at multiple pressure points, node stiffness, with a global FMS prevalence of 2.7%. Research shows that FMS is commonly encountered with various somatic diseases, such as rheumatoid arthritis, sicca syndrome, ankylosing spondylitis, osteoarthritis and the like. In the meantime, FMS is also commonly encountered with a variety of mental diseases, including depression, anxiety disorders, panic disorders, and post-traumatic stress disorder, with depression and anxiety disorders being most common with FMS (Bernikm, et al. Fibrous sympathology with instant disorders and preferences: combined medical and psychological treatment [ J ]. Current Panel Headrac Rep,2013,17 (9): 358 BuilaD, et al. Compliance of fibrous and psychological disorders J. Current Panel Headrac Rep,2007,11 (5): 333-338.). Investigations have shown that 25% to 30% of patients with FMS have major depression at the time of diagnosis, while the lifetime prevalence of FMS for depression and anxiety disorders is 74% and 60%, respectively. Meanwhile, depression also has certain physical symptoms, and pain is common. Currently, there have been reports of cases of fibromyalgia syndrome with depression (Dendrogen, yuanyin, ouiyi, et al. One example of fibromyalgia syndrome with depression [ J ]. J. Chinese J. Psychiatric, 2021,54 (6): 476-479.).
To date, the causes of FMS are still unknown, the pain is diverse in nature and difficult to relieve after rest, and the FMS is combined with the common disease manifestations of other body diseases and even mental diseases, so that the treatment difficulty is high, and the life quality and social functions of patients are seriously affected. Therefore, it is of great interest to explore drugs that are effective in the treatment of FMS.
With the rapid development of nanotechnology, the biomedical application of nanoenzymes prepared from nano wood materials simulating natural enzymes has become a research hotspot. The nano material of the mimic enzyme mainly comprises noble metal, transition metal sulfur/oxide, carbon-based nano material, metal organic framework material and the like. Molybdenum is a trace element and a nutrient necessary for the survival of all living bodies from bacteria, plants to humans, and is a cofactor for various molybdenum-based enzymes such as xanthine dehydrogenase, aldehyde oxidase, sulfite oxidase, which act as catalytic oxygen in biological systemsThe key components of the natural enzymes of redox and oxygen transfer reactions have been well documented. Currently, molybdenum-based nanoenzymes have been extensively studied, among which molybdenum carbide (Mo) 2 C) The nano enzyme has the characteristics of unique biochemical activity, high conductivity, high mechanical hardness, good thermal stability, flexible surface modification and the like. Hitherto, mo 2 Biomedical applications of C have involved cancer therapy, biosensing and biocatalysis, and have achieved a number of leading-edge efforts. However, the therapeutic effect on diseases such as FMS has not been reported.
Disclosure of Invention
The invention aims to provide a new application of molybdenum carbide.
The invention provides application of molybdenum carbide in preparing a medicament for treating fibromyalgia syndrome and/or depression.
Further, the molybdenum carbide is a molybdenum carbide nanosheet.
Further, the size of the molybdenum carbide nanosheet is 50 to 800nm, preferably 500nm.
Further, the above-mentioned drugs are pain-relieving drugs.
Furthermore, the medicine is used for relieving despair and anxiety.
The invention also provides a medicament which is a preparation prepared by taking molybdenum carbide as an active ingredient and adding pharmaceutically acceptable auxiliary materials.
Further, the molybdenum carbide is a molybdenum carbide nanosheet.
Further, the size of the molybdenum carbide nanosheet is 50 to 800nm, preferably 500nm.
Further, the above preparation is an injection.
Further, the above-mentioned supplementary material is physiological saline.
The invention has the beneficial effects that: the invention proves that the molybdenum carbide can relieve chronic pain, strengthen muscle strength, improve depression symptoms and provide a new choice for clinical treatment of fibromyalgia syndrome and/or depression.
It will be apparent that various other modifications, substitutions and alterations can be made in the present invention without departing from the basic technical concept of the invention as described above, according to the common technical knowledge and common practice in the field.
The present invention will be described in further detail with reference to the following examples. This should not be understood as limiting the scope of the above-described subject matter of the present invention to the following examples. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention.
Detailed Description
Mo of the invention 2 C nanoenzyme is two-dimensional Mo 2 C nanosheet (500 nm), purchased from Fushan neo-alkene nanomaterial science and technology Co. Mice were purchased from laboratory animal technology, limited, of Weitonglihua, beijing.
The remaining starting materials and equipment are, unless otherwise stated, known products, obtained by purchasing commercially available products.
Example 1, mo 2 Preparation of C nano enzyme injection
Mo 2 Mixing the nanometer C enzyme with normal saline to obtain injection.
The beneficial effects of the present invention are demonstrated by the following experimental examples.
Experimental example 1 therapeutic Effect of Mo2C nanoenzyme
1. Experimental methods
1.1Mo 2 Constructing a mouse model for treating muscle pain by using C nano enzyme:
the technique of reserpine-induced generation of muscle pain is a well established and widely used in vivo model. In an organism, reserpine may consume biogenic amines (including dopamine, 5-hydroxytryptamine, norepinephrine, and norepinephrine) to increase ROS levels to induce the production of muscle pain. Meanwhile, the construction of a depression model by utilizing reserpine is widely accepted. Thus. According to literature reports ([ 1)]Nociceptin/orphanin FQ receptor modulates painful and fatigue symptoms in a mouse model of fibromyalgia.[J].Pain,2019；[2]Therapeutic inhibition of inflammatory monocyte recruitment reduces steatohepatitis and liver fibrosis[J].Hepatology Official Journal of the American Association for the Study of Liver Diseases,2018.；[3]Development of mouse model for depression-induced by reserpine in Gao Xue Song, wang Yongzhi, li, etc. [ J ] research progress]Experimental animal science, 2017,34 (2): 57-61.doi, 10.3969/j, issn.1006-6179.2017.02.013, etc.), and the inventor's preliminary experiments, by continuous intraperitoneal injection of reserpine (1 mg/kg/d) for 3 days to male BALB/c mice for 8-10 weeks, muscle pain models and/or depression models can be successfully established, facilitating further exploration of Mo, and the like 2 C nano-enzyme has relieving effect on muscle pain and depression.
1.2 mice were grouped
Control group: 7 male BALB/c mice 8-10 weeks were injected with saline for 3 consecutive days.
Model group: 7 male BALB/c mice at 8-10 weeks were injected intraperitoneally with reserpine (1 mg/kg/d) continuously for 3 days.
Mo 2 Treatment group C: after 7 male BALB/c mice 8-10 weeks had been continuously intraperitoneally injected with reserpine (1 mg/kg/d) for 3 days, the Mo prepared in example 1 was injected into the tail vein 2 C nano enzyme injection (20 mg/kg) or normal saline, and behavioral assessment is carried out 24h after injection.
1.2 behavioral assessment of mice:
a. mechanical pain threshold detection: the mouse is placed in an organic transparent glass cover on a steel wire mesh frame with small holes, adaptive movement is carried out for 30min, two von Frey fiber needles with different stimulation intensities, namely 0.07g and 0.4g, are utilized to vertically contact the central part of the hind paw of the mouse through the small holes below the steel wire mesh frame, then pressure is applied to enable the needles to bend and stimulate the hind paw, and whether the hind paw of the mouse is lifted or not is observed. The duration of stimulation is 1.5s at the maximum, the time interval between two times of stimulation is more than 5min, the stimulation is carried out for 10 times, and the times of the foot-contracting reaction of the mouse in 10 times of detection are recorded. Wherein the percentage of the times of leg contraction reaction obtained by 0.07g of stimulation to the soles of the mice is called the frequency of hyperalgesia reaction, and the percentage of the times of leg contraction reaction obtained by 0.4g of stimulation is called the frequency of hyperalgesia reaction;
b. heat stimulation paw withdrawal latency: the mice were placed in a transparent plexiglass hood and placed over the pain-measuring instrument glass plate and allowed to move acclimatically for 30min until quiet. And 2-3min before measurement, turning on an instrument power switch to preheat the machine, and then adjusting the intensity of a radiation light source and the parameters of the radiation photo-thermal pain detector to maintain the basal value of the thermal stimulation foot contraction latency of the mouse at 10s. And then starting detection, moving the infrared light source to the middle part of the rear sole of the mouse, starting a start key, starting the test, simultaneously starting timing by a digital timer, and stopping timing by an instrument key and displaying the duration time on a display when the pain prompts the mouse to lift the rear foot. This time is the heat stimulation paw withdrawal latency. In order to avoid mouse injury caused by stimulating thermal stimulation, the maximum thermal stimulation upper limit time is set to be 20s. The hind paw of each mouse needs to be measured repeatedly for 5 times, each time is separated by 5min, and the average value is the final heat stimulation paw withdrawal latent period.
c. And (3) detecting the holding power: lifting the tail of the mouse, recording the maximum gripping force of the forelimb of the mouse for gripping the grid, recording 6 times of experiments and taking an average value;
d. forced swimming experiment: putting the mouse into a glass round jar with the water depth of 10cm, swimming for 6min at the water temperature of 25 ℃, and recording the accumulated immobile time of the mouse within 4 min;
e. elevated plus maze: the mouse is lightly placed in the central area of the uterine body of the instrument, the animal faces to the open arm, and then the experimenter leaves the instrument quickly and quietly; and recording the times of entering the open arm, the duration time in the open arm, the times of closing the arm and the movement time of closing the arm, and calculating the total times of entering the open arm and the closed arm, the proportion of the times of entering the open arm and the proportion of the stay time of the open arm.
2. Results of the experiment
(1) In the mechanical pain threshold test, the frequency of the allodynia reaction and the frequency of the hyperalgesia reaction in the model group are significantly increased compared with those in the control group. And Mo 2 The frequency of hyperalgesia and hyperalgesia in the treatment group C was significantly reduced.
(2) In the heat stimulus paw withdrawal latency test, the latency time of exposure to the heat stimulus in the heat allergy test (10.8 s) was significantly reduced in the model group compared to the control (15.2 s) group. In contrast, mo 2 C treatment prevented thermal pain and was effective in curing the pain caused by reserpine to normal levels (14.7 s).
(3) In the forced swim test, compared to the control group (103.7 seconds),the immobility time of the model group mice was significantly increased (164.8 s). And Mo 2 The immobility time was significantly reduced in the C treatment group (91.2 seconds).
(4) Grip loss (1.4N) ratio Mo of model group in grip strength test 2 The treatment group C (1.6N) and the control group (1.8N) were more significant.
(5) In the elevated plus maze test, the movement activity of the model group is weakened, and the total entry times (8.2 times) of the opening and closing arms are obviously reduced compared with the control group (18.1 times). To give Mo 2 C treated Mo 2 The activity was significantly improved in the treatment group C (15.7 times). Furthermore, the time taken for the model set to enter the opening and closing arms is much lower than Mo 2 C treatment group and control group.
In conclusion, the molybdenum carbide nanoenzyme provided by the invention has the effects of relieving chronic pain and improving muscle strength and improving depression symptoms, and provides a new choice for clinical treatment of fibromyalgia syndrome and/or depression.

Claims (10)

1. Use of molybdenum carbide for the manufacture of a medicament for the treatment of fibromyalgia syndrome and/or depression.
2. Use according to claim 1, wherein the molybdenum carbide is molybdenum carbide nanoplates.
3. Use according to claim 2, wherein the molybdenum carbide nanoplates have a size of 50-800 nm, preferably 500nm.
4. Use according to any one of claims 1 to 3, wherein the medicament is a pain-relieving medicament.
5. The use according to any one of claims 1 to 3, wherein the medicament is a medicament for relieving despair, anxiety mood.
6. The medicine is characterized in that the medicine is a preparation prepared by taking molybdenum carbide as an active ingredient and adding pharmaceutically acceptable auxiliary materials.
7. The drug of claim 6, wherein the molybdenum carbide is molybdenum carbide nanoplates.
8. Pharmaceutical according to claim 7, characterized in that the size of the molybdenum carbide nanoplates is between 50 and 800nm, preferably 500nm.
9. The medicament of claim 6, wherein the formulation is an injectable solution.
10. The medicament of claim 9, wherein the excipient is normal saline.
CN202210868657.4A 2022-07-22 2022-07-22 Use of molybdenum carbide in preparation of medicament for treating fibromyalgia syndrome and/or depression Pending CN115381853A (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113667633A (en) * 2021-07-29 2021-11-19 四川大学华西医院 Method for constructing cortical organoid model of schizophrenia dysplasia
CN114028396A (en) * 2021-12-10 2022-02-11 北京大学第三医院（北京大学第三临床医学院） Application of tetrandrine in preparation of medicine for treating fibromyalgia

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113667633A (en) * 2021-07-29 2021-11-19 四川大学华西医院 Method for constructing cortical organoid model of schizophrenia dysplasia
CN114028396A (en) * 2021-12-10 2022-02-11 北京大学第三医院（北京大学第三临床医学院） Application of tetrandrine in preparation of medicine for treating fibromyalgia

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DINGKUN ZHANG ET AL.: "Integrated metabolomics revealed the fibromyalgia-alleviation effect of Mo2C nanozyme through regulated homeostasis of oxidative stress and energy metabolism", BIOMATERIALS, pages 2 - 3 *
张文钲;: "钼基催化剂技术发展现状", 中国钼业, no. 02 *

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