Application of radiofrequency device in the treatment of facial paralysis associated with movement
Through the combined use of radiofrequency surgery and pharmaceutical compositions, the problem of lack of effective treatment methods for facial paralysis and exercise is solved, significantly improving symptoms, reducing side effects, and improving treatment safety and effectiveness.
Patent Information
- Application Number
- CN202311159251.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Priority Date
- 2022-09-09
- Filing Date
- 2023-09-09
- Publication Date
- 2025-05-23
- Estimated Expiration
- 2043-09-09
AI Technical Summary
Facial paralysis and exercise are a symptom that seriously affects patients' lives and work, and the existing technology lacks effective treatment methods.
The pulsed radio frequency surgery is performed using a radio frequency device, combined with specific voltage, frequency and temperature conditions, combined with pharmaceutical compositions and rehabilitation training exercises, and is used to treat facial paralysis and joint exercises.
Through the combined use of radiofrequency surgery and pharmaceutical compositions, the joint motor symptoms of facial paralysis are significantly improved, side effects are reduced, and treatment safety and effectiveness are improved.
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Abstract
Description
Technical Field
[0001] The present invention belongs to the field of biomedicine, and specifically relates to an application of a radio frequency device in treating facial paralysis-related movements. Background Art
[0002] Facial paralysis associated movement is a complication of facial paralysis. Common clinical associated movement symptoms include slight tremor of the upper lip on the affected side when the patient blinks; involuntary closure of the affected eye when showing teeth; contraction of the frontal muscle on the affected side when trying to close the eyes; tears on the affected side when eating and chewing, accompanied by temporal skin flushing and local fever. The proportion of moderate to severe peripheral facial paralysis combined with associated movement in the middle and late stages is as high as 60%-70%. Facial paralysis associated movement seriously affects the patient's self-confidence, work and life, and there is a lack of effective treatment. The new hypothesis of the pathogenesis of facial paralysis associated movement includes facial nerve scar repair, micro-facial neuroma formation, increased entropy of the facial nerve, and the change of neural pathways from order to disorder after facial nerve injury. So far, there are no effective drugs and treatment plans for the treatment of facial paralysis associated movement in clinical practice.
[0003] Radiofrequency technology is a minimally invasive interventional technology. Continuous radiofrequency (conventional radiofrequency, CRF) can easily cause tissue protein denaturation, damage nerves, prevent the conduction of pain signals, and damage target tissues, among other side effects. The radiofrequency energy of pulsed radiofrequency (pulsed radiofrequency, PRF) is sufficient to increase the radiofrequency field effect without causing tissue damage, and is a safe and effective method for treating pain. Radiofrequency thermocoagulation is an improved pain treatment technology. Traditional PRF technology emits radiofrequency current for 20ms each time, followed by a 480ms interval, so that the heat has time to diffuse to the surrounding tissues, and the target temperature does not exceed 42°C, so it does not cause local tissue degeneration. It regulates nerve function without causing nerve tissue damage or blocking nerve conduction; it uses high voltage and pulsed current to generate voltage fluctuations, and the interval period allows the heat generated by the radiofrequency current near the nerve tissue to diffuse, ensuring that the tip temperature does not exceed 42°C, and does not cause local tissue degeneration; Kapural studies have shown that compared with monopolar radiofrequency, bipolar radiofrequency can produce a wider range of action.
[0004] Patent applications (CN2023100429139, PCT / CN2023 / 073566, CN2023100429143, PCT / CN2023 / 073582) disclose technical contents related to nerve repair protein extracts and nerve repair protein compositions with repair effects. The aforementioned applications and contents serve as indispensable technical references and components of this application. Summary of the invention
[0005] The purpose of the present invention is to provide an application of a radio frequency device in treating facial paralysis-related movements.
[0006] In the preferred technical solution of the present invention, the radio frequency surgery is based on long-term temperature-controlled high-voltage variable-frequency pulse radio frequency for 800 seconds to 1400 seconds under the conditions of 41°C-42°C, 90V-140V, and 2Hz-6Hz.
[0007] In the preferred technical solution of the present invention, the radio frequency surgery is based on long-term temperature-controlled high-voltage variable-frequency pulse radio frequency for 960 seconds to 1200 seconds under the conditions of 41°C-42°C, 100V-120V, and 3Hz-5Hz.
[0008] In the preferred technical solution of the present invention, the radiofrequency surgery is optionally used in combination with any one or a combination of a pharmaceutical composition for preventing and treating facial paralysis-associated movements and rehabilitation training exercises.
[0009] In the preferred technical solution of the present invention, the treatment plan for preventing and treating facial paralysis associated with movement is pulsed radiofrequency surgery, postoperative oral medication and acupoint injection medication, and intraoperative and postoperative rehabilitation exercise training.
[0010] In the preferred technical scheme of the present invention, the rehabilitation training exercises are facial paralysis rehabilitation training exercises originally created by the inventor (copyright registration number: Guozuo Dengzi-2022-I-10250228 and copyright registration number: Guozuo Dengzi-2022-F-10250229).
[0011] In the preferred technical solution of the present invention, the rehabilitation exercise training is selected from any one of the first set of rehabilitation exercise training and the second set of rehabilitation exercise training or a combination thereof.
[0012] In the preferred technical scheme of the present invention, the first set of rehabilitation exercises includes: first, looking in the mirror; second, slowly closing the eyes, closing the eyes for 5 seconds, and then opening the eyes and keeping them for 5 seconds, while controlling the corners of the mouth to not have any upward movement, and correcting the associated movement; the first set of rehabilitation exercises is trained three times a day, and each set is trained 30 times.
[0013] In the preferred technical solution of the present invention, the second set of rehabilitation exercises includes: first, looking in the mirror; second, opening eyes and keeping the nerve branches silent as much as possible; third, pursing lips, baring teeth and puffing cheeks around the mouth; and performing three sets of the first set of rehabilitation exercises every day, with each set of exercises performed 10 times.
[0014] In the preferred technical scheme of the present invention, the facial paralysis is selected from any one or a combination of hemifacial spasm, facial paralysis / associated movement, trigeminal neuralgia, glossopharyngeal neuralgia, facial neuritis, peripheral facial paralysis, and eye muscle spasm repair.
[0015] In the preferred technical scheme of the present invention, the pharmaceutical composition for preventing and treating facial paralysis associated with movement is selected from mouse nerve growth factor, monosialoganglioside (GM1), cerebroside carnosine, methylcobalamin, adenosylcobalamin, vitamin B complex, butylphthalide, cinepazide maleate, edaravone, edaravone dextroborneol, citicoline, citicoline sodium, ganglioside, oxiracetam, brain protein, piracetam, nerve growth factor, citicoline, neurotropin, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin E, compound brain peptide ganglioside, aniracetam, neuraminic acid, any one or a combination of a nerve repair cell protein extract or a nerve repair protein composition with repair efficacy.
[0016] In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating facial paralysis with associated movements contains any one of mouse nerve growth factor, methylcobalamin, and adenosine cobalt or a combination thereof.
[0017] In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating facial paralysis-associated movement consists of a pharmaceutical composition for single oral administration and a pharmaceutical composition for single acupoint injection.
[0018] In a preferred technical solution of the present invention, the pharmaceutical composition for single administration contains any one of 0.5-1.0 mg of methylcobalamin and 0.1-0.5 mg of adenosylcobalamin or a combination thereof.
[0019] In the preferred technical scheme of the present invention, the dosage regimen of the oral pharmaceutical composition is: oral administration of methylcobalamin 0.5 mg / time, 3-4 times / day, every other month; adenosylcobalamin 0.5 mg / time, 3 times / day, for 3 consecutive weeks, stop for 1 week, and then continue to repeat for half a year;
[0020] In a preferred technical solution of the present invention, the oral pharmaceutical composition is selected from any one or a combination of simultaneous administration or sequential administration.
[0021] In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is a combination of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, and 200mg of vitamin B1.
[0022] In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupoint injection contains any one of 30-90ug of mouse nerve growth factor, 0.5-1.0mg of methylcobalamin, 0.1-0.5mg of adenosylcobalamin, and 2-5mg of dexamethasone or a combination thereof.
[0023] In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupuncture point injection is any one or a combination of mouse nerve growth factor 30-90ug, methylcobalamin 0.5-1.0mg, adenosylcobalamin 0.1-0.5mg, dexamethasone 2-5mg, 100-300mg of nerve repair cell protein extract and / or nerve repair protein composition with repair efficacy.
[0024] In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 2mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.
[0025] In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.
[0026] In the preferred technical scheme of the present invention, in the composition, the pharmaceutical composition for single acupoint injection consists of 90ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.
[0027] In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupoint injection consists of 60ug of mouse nerve growth factor, 0.8mg of methylcobalamin, 0.5mg of adenosylcobalamin, 3mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.
[0028] In a preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection optionally contains 100-300 mg of any one or a combination of a nerve repair cell protein extract and / or a nerve repair protein composition having a repair effect.
[0029] In a preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is prepared and used immediately.
[0030] In the preferred technical solution of the present invention, Yangbai point, temple, Sibai point, Yingxiang point, Juliao point, Dicang point and Jiache point on the affected side of the face are selected for acupoint injection.
[0031] In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is injected into the acupoint once a day, and the treatment course is 7 days.
[0032] In the preferred technical solution of the present invention, each acupoint injection treatment lasts for 2-6 courses, preferably 4-5 courses.
[0033] Another object of the present invention is to provide a pharmaceutical composition for preventing and treating facial paralysis associated with movement, selected from rat nerve growth factor, monosialoganglioside (GM1), cerebroside carnosine, methylcobalamin, adenosylcobalamin, vitamin B complex, butylphthalide, cinepazide maleate, edaravone, edaravone dextroborneol, citicoline, citicoline sodium, ganglioside, oxiracetam, brain protein, piracetam, nerve growth factor, citicoline, neurotropin, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin E, compound brain peptide ganglioside, aniracetam, neuraminic acid, any one or a combination thereof, of a nerve repair cell protein extract or a nerve repair protein composition having a repair effect.
[0034] In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating facial paralysis with associated movements contains any one of mouse nerve growth factor, methylcobalamin, and adenosine cobalt or a combination thereof.
[0035] In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating facial paralysis-associated movement consists of a pharmaceutical composition for single oral administration and a pharmaceutical composition for single acupoint injection.
[0036] In a preferred technical solution of the present invention, the pharmaceutical composition for single administration contains any one of 0.5-1.0 mg of methylcobalamin and 0.1-0.5 mg of adenosylcobalamin or a combination thereof.
[0037] In the preferred technical scheme of the present invention, the dosage regimen of the oral pharmaceutical composition is: oral administration of methylcobalamin 0.5 mg / time, 3-4 times / day, every other month; adenosylcobalamin 0.5 mg / time, 3 times / day, for 3 consecutive weeks, stop for 1 week, and then continue to repeat for half a year;
[0038] In a preferred technical solution of the present invention, the oral pharmaceutical composition is selected from any one or a combination of simultaneous administration or sequential administration.
[0039] In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is a combination of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, and 200mg of vitamin B1.
[0040] In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupoint injection contains any one of 30-90ug of mouse nerve growth factor, 0.5-1.0mg of methylcobalamin, 0.1-0.5mg of adenosylcobalamin, and 2-5mg of dexamethasone or a combination thereof.
[0041] In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupuncture point injection is any one or a combination of mouse nerve growth factor 30-90ug, methylcobalamin 0.5-1.0mg, adenosylcobalamin 0.1-0.5mg, dexamethasone 2-5mg, 100-300mg of nerve repair cell protein extract and / or nerve repair protein composition with repair efficacy.
[0042] In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 2mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.
[0043] In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.
[0044] In the preferred technical scheme of the present invention, in the composition, the pharmaceutical composition for single acupoint injection consists of 90ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.
[0045] In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupoint injection consists of 60ug of mouse nerve growth factor, 0.8mg of methylcobalamin, 0.5mg of adenosylcobalamin, 3mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.
[0046] In a preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection optionally contains 100-300 mg of any one or a combination of a nerve repair cell protein extract and / or a nerve repair protein composition having a repair effect.
[0047] In a preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is prepared and used immediately.
[0048] In the preferred technical solution of the present invention, Yangbai point, temple, Sibai point, Yingxiang point, Juliao point, Dicang point and Jiache point on the affected side of the face are selected for acupoint injection.
[0049] In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is injected into the acupoint once a day, and the treatment course is 7 days.
[0050] In the preferred technical solution of the present invention, each acupoint injection treatment lasts for 2-6 courses, preferably 4-5 courses.
[0051] In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating facial paralysis-associated movement is optionally used in combination with any one of radiofrequency surgery and rehabilitation training exercises or a combination thereof.
[0052] In the preferred technical solution of the present invention, the radio frequency surgery is based on long-term temperature-controlled high-voltage variable-frequency pulse radio frequency for 800 seconds to 1400 seconds under the conditions of 41°C-42°C, 90V-140V, and 2Hz-6Hz.
[0053] In the preferred technical solution of the present invention, the radio frequency surgery is based on long-term temperature-controlled high-voltage variable-frequency pulse radio frequency for 960 seconds to 1200 seconds under the conditions of 41°C-42°C, 100V-120V, and 3Hz-5Hz.
[0054] In the preferred technical scheme of the present invention, the rehabilitation training exercises are facial paralysis rehabilitation training exercises originally created by the inventor (copyright registration number: Guozuo Dengzi-2022-I-10250228 and copyright registration number: Guozuo Dengzi-2022-F-10250229).
[0055] In the preferred technical solution of the present invention, the rehabilitation exercise training is selected from any one of the first set of rehabilitation exercise training and the second set of rehabilitation exercise training or a combination thereof.
[0056] In the preferred technical scheme of the present invention, the first set of rehabilitation exercises includes: first, looking in the mirror; second, slowly closing the eyes, closing the eyes for 5 seconds, and then opening the eyes and keeping them for 5 seconds, while controlling the corners of the mouth to not have any upward movement, and correcting the associated movement; the first set of rehabilitation exercises is trained three times a day, and each set is trained 30 times.
[0057] In the preferred technical solution of the present invention, the second set of rehabilitation exercises includes: first, looking in the mirror; second, opening eyes and keeping the nerve branches silent as much as possible; third, pursing lips, baring teeth and puffing cheeks around the mouth; and performing three sets of the first set of rehabilitation exercises every day, with each set of exercises performed 10 times.
[0058] In the preferred technical solution of the present invention, the treatment plan for preventing and treating facial nerve paralysis in the recovery period is pulsed radiofrequency surgery, postoperative oral medication and acupoint injection medication, and intraoperative and postoperative rehabilitation exercise training.
[0059] In the preferred technical scheme of the present invention, the facial nerve paralysis is selected from any one of hemifacial spasm, facial paralysis / associated movement, trigeminal neuralgia, glossopharyngeal neuralgia, facial neuritis, peripheral facial paralysis, and eye muscle spasm repair, or a combination thereof.
[0060] Another object of the present invention is to provide a treatment plan for preventing and treating facial paralysis-related movements, which includes a pharmaceutical composition for preventing and treating facial paralysis-related movements, optionally used in combination with any one of radiofrequency surgery and rehabilitation exercises or a combination thereof.
[0061] In the preferred technical scheme of the present invention, the pharmaceutical composition for preventing and treating facial paralysis associated with movement is selected from mouse nerve growth factor, monosialoganglioside (GM1), cerebroside carnosine, methylcobalamin, adenosylcobalamin, vitamin B complex, butylphthalide, cinepazide maleate, edaravone, edaravone dextroborneol, citicoline, citicoline sodium, ganglioside, oxiracetam, brain protein, piracetam, nerve growth factor, citicoline, neurotropin, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin E, compound brain peptide ganglioside, aniracetam, neuraminic acid, any one or a combination of a nerve repair cell protein extract or a nerve repair protein composition with repair efficacy.
[0062] In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating facial paralysis with associated movements contains any one of mouse nerve growth factor, methylcobalamin, and adenosine cobalt or a combination thereof.
[0063] In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating facial paralysis-associated movement consists of a pharmaceutical composition for single oral administration and a pharmaceutical composition for single acupoint injection.
[0064] In a preferred technical solution of the present invention, the pharmaceutical composition for single administration contains any one of 0.5-1.0 mg of methylcobalamin and 0.1-0.5 mg of adenosylcobalamin or a combination thereof.
[0065] In the preferred technical scheme of the present invention, the dosage regimen of the oral pharmaceutical composition is: oral administration of methylcobalamin 0.5 mg / time, 3-4 times / day, every other month; adenosylcobalamin 0.5 mg / time, 3 times / day, for 3 consecutive weeks, stop for 1 week, and then continue to repeat for half a year;
[0066] In a preferred technical solution of the present invention, the oral pharmaceutical composition is selected from any one or a combination of simultaneous administration or sequential administration.
[0067] In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is a combination of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, and 200mg of vitamin B1.
[0068] In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupoint injection contains any one of 30-90ug of mouse nerve growth factor, 0.5-1.0mg of methylcobalamin, 0.1-0.5mg of adenosylcobalamin, and 2-5mg of dexamethasone or a combination thereof.
[0069] In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupuncture point injection is any one or a combination of mouse nerve growth factor 30-90ug, methylcobalamin 0.5-1.0mg, adenosylcobalamin 0.1-0.5mg, dexamethasone 2-5mg, 100-300mg of nerve repair cell protein extract and / or nerve repair protein composition with repair efficacy.
[0070] In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 2mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.
[0071] In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.
[0072] In the preferred technical scheme of the present invention, in the composition, the pharmaceutical composition for single acupoint injection consists of 90ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.
[0073] In the preferred technical scheme of the present invention, the pharmaceutical composition for single acupoint injection consists of 60ug of mouse nerve growth factor, 0.8mg of methylcobalamin, 0.5mg of adenosylcobalamin, 3mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.
[0074] In a preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection optionally contains 100-300 mg of any one or a combination of a nerve repair cell protein extract and / or a nerve repair protein composition having a repair effect.
[0075] In a preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is prepared and used immediately.
[0076] In the preferred technical solution of the present invention, Yangbai point, temple, Sibai point, Yingxiang point, Juliao point, Dicang point and Jiache point on the affected side of the face are selected for acupoint injection.
[0077] In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is injected into the acupoint once a day, and the treatment course is 7 days.
[0078] In the preferred technical solution of the present invention, each acupoint injection treatment lasts for 2-6 courses, preferably 4-5 courses.
[0079] In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating facial paralysis-associated movement is optionally used in combination with any one of radiofrequency surgery and rehabilitation training exercises or a combination thereof.
[0080] In the preferred technical solution of the present invention, the radio frequency surgery is based on long-term temperature-controlled high-voltage variable-frequency pulse radio frequency for 800 seconds to 1400 seconds under the conditions of 41°C-42°C, 90V-140V, and 2Hz-6Hz.
[0081] In the preferred technical solution of the present invention, the radio frequency surgery is based on long-term temperature-controlled high-voltage variable-frequency pulse radio frequency for 960 seconds to 1200 seconds under the conditions of 41°C-42°C, 100V-120V, and 3Hz-5Hz.
[0082] In the preferred technical scheme of the present invention, the rehabilitation training exercises are facial paralysis rehabilitation training exercises originally created by the inventor (copyright registration number: Guozuo Dengzi-2022-I-10250228 and copyright registration number: Guozuo Dengzi-2022-F-10250229).
[0083] In the preferred technical solution of the present invention, the rehabilitation exercise training is selected from any one of the first set of rehabilitation exercise training and the second set of rehabilitation exercise training or a combination thereof.
[0084] In the preferred technical scheme of the present invention, the first set of rehabilitation exercises includes: first, looking in the mirror; second, slowly closing the eyes, closing the eyes for 5 seconds, and then opening the eyes and keeping them for 5 seconds, while controlling the corners of the mouth to not have any upward movement, and correcting the associated movement; the first set of rehabilitation exercises is trained three times a day, and each set is trained 30 times.
[0085] In the preferred technical solution of the present invention, the second set of rehabilitation exercises includes: first, looking in the mirror; second, opening eyes and keeping the nerve branches silent as much as possible; third, pursing lips, baring teeth and puffing cheeks around the mouth; and performing three sets of the first set of rehabilitation exercises every day, with each set of exercises performed 10 times.
[0086] In the preferred technical solution of the present invention, the treatment plan for preventing and treating facial nerve paralysis in the recovery period is pulsed radiofrequency surgery, postoperative oral medication and acupoint injection medication, and intraoperative and postoperative rehabilitation exercise training.
[0087] In the preferred technical scheme of the present invention, the facial nerve paralysis is selected from any one of hemifacial spasm, facial paralysis / associated movement, trigeminal neuralgia, glossopharyngeal neuralgia, facial neuritis, peripheral facial paralysis, and eye muscle spasm repair, or a combination thereof.
[0088] In order to clearly describe the present invention, the nerve repair cell protein extract or nerve repair cell protein composition with repair efficacy described in the present invention is prepared with reference to patent applications (CN2023100429139, PCT / CN2023 / 073566, CN2023100429143, PCT / CN2023 / 073582).
[0089] In the preferred technical solution of the present invention, the method for preparing the nerve repair cell protein extract having nerve repair efficacy comprises the following steps:
[0090] S-1: The density is 5.0×10 6 / mL-5.0×10 7 Mesenchymal stem cells (100 g / mL) were placed in a culture medium containing 40-50% DMEM / F12, 40-50% RPMI1640, 0.1-2% bovine serum albumin (BSA), 1-15ug / mL epidermal growth factor (EGF), 1-15ug / mL fibroblast growth factor (FGF), 1-15ug / mL insulin transferrin, 0.01-0.1% compound amino acid (18AA) and 2-10μmol / L stressor, and then placed at 37.0°C ± 0.5°C, 5% ± 1.0% CO 2 After culturing for 2h-6h under the conditions, separating, washing and collecting the cells, wherein the stressor is selected from any one or a combination of compounds 1-16;
[0091]
[0092]
[0093] S-2: Collect cells at a density of 5.0×10 6 / mL-5.0×10 7 pcs / mL is dispersed in a solvent, and then subjected to ultrasonic treatment at 2°C-8°C to obtain a cell lysate, wherein the solvent is selected from any one of physiological saline, 5% glucose solution, phosphate buffered saline (PBS), TBPS buffer, TBST buffer, and Tris buffer or a combination thereof;
[0094] S-3: After the cell lysate obtained in step S-2 is separated, the obtained separation solution is filtered through 0.45um and 0.22um filter membranes in sequence.
[0095] In the preferred technical scheme of the present invention, the culture medium of step S-1 contains DMEM / F12 42-45%, RPMI164042-45%, bovine serum albumin (BSA) 0.5-1.5%, epidermal growth factor (EGF) 5-10ug / mL, fibroblast growth factor (FGF) 5-10ug / mL, insulin transferrin 5-10ug / mL, compound amino acid (18AA) 0.02-0.05% and 3-8μmol / L of stressor.
[0096] In the preferred technical scheme of the present invention, the culture medium of step S-1 contains DMEM / F12 45%, RPMI164045%, bovine serum albumin (BSA) 0.5%, epidermal growth factor (EGF) 10ug / mL, fibroblast growth factor (FGF) 10ug / mL, insulin transferrin 10ug / mL, compound amino acid (18AA) 0.05% and 4-6μmol / L of stressor.
[0097] In the preferred technical solution of the present invention, the density of mesenchymal stem cells in step S-1 is 8.0×10 6 -2.0×10 7 / mL, preferably 8.0×10 6 -1.0×10 7 Pieces / mL.
[0098] In a preferred technical solution of the present invention, the mesenchymal stem cells in step S-1 are cultured in the culture medium for 3h-5h, preferably 3.5h-4.5h.
[0099] In a preferred technical solution of the present invention, the solvent for washing cells in step S-1 is selected from any one of physiological saline, 5% glucose solution, phosphate buffered saline (PBS), TBPS buffer, TBST buffer, Tris buffer or a combination thereof, and the number of cell washing times is 2-5 times, preferably 3-4 times.
[0100] In the preferred technical scheme of the present invention, the separation described in step S-1 is selected from any one of centrifugation and filtration or a combination thereof, wherein the centrifugation conditions are 1000-2000rpm*3-15min, preferably 1200rpm-1500rpm*5-10min.
[0101] In the preferred technical solution of the present invention, the ultrasonic conditions of step S-2 are: working for 3s and then resting for 1s at 2°C-8°C, 25kHZ, 360W, and ultrasonic treatment for 1-5min.
[0102] In the preferred technical solution of the present invention, the separation in step S-3 is selected from any one of 2000-8000rpm*10-30min centrifugation, multi-stage centrifugation, multi-stage filtration or a combination thereof, preferably 3000-7000rpm*15-25min.
[0103] In the preferred technical solution of the present invention, the multi-stage centrifugation in step S-3 is 3000-4000rpm*3-5min, 5000-6000rpm*3-5min and 7000rpm*5-8min respectively.
[0104] In the preferred technical solution of the present invention, the pore size of the filter membrane for multi-stage filtration is selected from any one of 80um, 50um, 30um, 10um, and 5um.
[0105] In a preferred technical solution of the present invention, the cell protein extract obtained in step S-3 is frozen, preferably at -40°C to -20°C.
[0106] In a preferred technical solution of the present invention, the cell protein extract obtained in step S-3 is hydrolyzed by either nuclease or omnipotent nuclease and then separated and purified.
[0107] In a preferred technical solution of the present invention, the culture of the mesenchymal stem cells or the culture of the primary mesenchymal stem cells adopts a culture method in the art.
[0108] In the preferred technical solution of the present invention, the culture of mesenchymal stem cells comprises the following steps: primary mesenchymal stem cells are cultured at an initial density of 5.0×10 5 -5.0×10 6 100 μg / ml was added to the subculture medium, which was then placed at 37.0°C ± 0.5°C and 5% ± 1.0% CO 2 The cells were cultured under the same conditions for 10-15 days, and the subculture medium was replaced by half every 2-3 days after the culture medium turned yellow. The subculture medium contained DMEM / F12 medium containing 10% FBS, 100U / ml penicillin and 100ug / ml streptomycin.
[0109] In the preferred technical solution of the present invention, the culture of primary mesenchymal stem cells comprises the following steps:
[0110] 1) After cleaning and disinfecting the umbilical cord, dissect the tissue, take the Wharton's jelly tissue, and cut it into 3mm 3 The tissue blocks were collected by centrifugation, washing, and placed in DMEM / F12 medium containing 10% fetal bovine serum FBS, 100ug / ml penicillin, and 100ug / ml streptomycin, and then placed at 37.0℃±0.5℃, 5%±1.0% CO 2Culture under the same conditions, replace half of the medium every 2-3 days, and culture until the tissue mass crawls out of the cells;
[0111] 2) Shake and collect the lower layer cells, wash with PBS, add 0.25% trypsin to digest for 2min-3min, add an equal volume of trypsin stop solution to stop digestion, pipette gently to blow, centrifuge at 1200-1500rpm / min*5-8min, and collect the cells.
[0112] Unless otherwise specified, when the present invention relates to the percentage between liquids, the percentage is volume / volume percentage; when the present invention relates to the percentage between liquids and solids, the percentage is volume / weight percentage; when the present invention relates to the percentage between solids and liquids, the percentage is weight / volume percentage; the rest are weight / weight percentages.
[0113] Unless otherwise stated, the present invention is evaluated using the following method:
[0114] 1. Acupoint selection: The acupoints are located according to the National Standard of the People's Republic of China "Names and Locations of Acupoints" (GB / T 12345-2006) issued by the State Bureau of Technical Supervision.
[0115] 2. Facial paralysis motor function evaluation scale
[0116] 3. Facial Paralysis Quality of Life Assessment Scale
[0117] Compared with the prior art, the present invention has the following beneficial effects:
[0118] 1. The present invention adopts a radio frequency method for the treatment of facial paralysis-associated movements, does not require open surgery, avoids the trauma and pain of traditional treatment, and is combined with a pharmaceutical composition for the treatment of associated movements. The components synergize with each other, the pharmaceutical composition has a fast onset of action, a prolonged duration of action, and a good therapeutic effect. It can reduce the side effects caused by the use of a single drug, and at the same time accelerate the improvement of facial paralysis symptoms. The treatment is safe and reliable, and there are no obvious side effects and complications.
[0119] 2. The present invention can save the amount of drugs used, significantly reduce production costs, is easy to operate, and is suitable for large-scale industrial production. DETAILED DESCRIPTION
[0120] The details of the present invention are further explained and described below in conjunction with specific embodiments, but the protection scope of the present invention is not limited thereto.
[0121] Example 1 Preparation of nerve repair cell protein extract with repair effect
[0122] 1. Culture of primary mesenchymal stem cells
[0123] The culture of primary mesenchymal stem cells includes the following steps:
[0124] 1) After cleaning and disinfecting the umbilical cord, dissect the tissue, take the Wharton's jelly tissue, and cut it into 3mm 3 The tissue blocks were collected by centrifugation, washed, and placed in a culture bottle. DMEM / F12 medium containing 10% fetal bovine serum (FBS), 100ug / ml penicillin, and 100ug / ml streptomycin was added, and then placed at 37°C and 5% CO. 2 Culture under the appropriate conditions to promote adhesion. After the culture medium turns yellow every 2-3 days, replace half of the culture medium. Culture for 10-12 days until cells can be seen crawling out of the edge of the tissue block.
[0125] 2) Gently shake the tissue blocks to make them fall off, collect the tissue blocks and the lower layer cells respectively, and culture the collected tissue blocks again on the wall;
[0126] 3) After washing the collected lower layer cells with PBS, add an appropriate amount of 0.25% trypsin to digest for 2min-3min, add an equal volume of trypsin stop solution to stop digestion, gently blow the bottom of the bottle with a pipette, centrifuge at 1500rpm*5min, and collect the cells.
[0127] 2. Subculture of primary mesenchymal stem cells (Cultivation of mesenchymal stem cells)
[0128] Subculture of primary mesenchymal stem cells (culture of mesenchymal subcultured stem cells): primary mesenchymal stem cells were cultured at an initial density of 5.0×10 5 -5.0×10 6 100 μg / ml was added to DMEM / F12 medium containing 10% FBS, 100 U / ml penicillin and 100 μg / ml streptomycin, and then placed at 37.0°C ± 0.5°C and 5% ± 1.0% CO 2 Culture under the same conditions for 10-15 days, and replace half of the culture medium every 2-3 days after the culture medium turns yellow.
[0129] 3. The preparation of compounds 1-16 refers to document 1 (New limonophyllines AC from the stem of Atalantia monophylla and cytotoxicity against cholangiocarcinoma and HepG2 cell lines, Arch. Pharm. Res. (2018) 41: 431-437).
[0130] A method for preparing a nerve repair cell protein extract having a nerve repair effect comprises the following steps:
[0131] (1) Mesenchymal cells were cultured at a density of 8.0×10 6 10 μg / mL was added to a medium containing DMEM / F12 45%, RPMI1640 45%, bovine serum albumin (BSA) 0.5%, epidermal growth factor (EGF) 10 μg / mL, fibroblast growth factor (FGF) 10 μg / mL, insulin transferrin 10 μg / mL, compound amino acid (18AA) 0.05% and 5 μmol / L of compound 16, and then placed at 37°C, 5% CO 2 After culturing for 4 h under the same conditions, the cells were centrifuged at 1200 rpm for 5 min, washed three times with PBS, and then the cells were collected;
[0132] (2) The cells collected in step (1) were cultured at a density of 1.0×10 7 Cells were dispersed in normal saline and sonicated for 3s, 1s at rest, and 2min at 2-8°C, 25kHz, and 360W to obtain cell lysate.
[0133] (3) centrifuging the cell lysate obtained in step (2) at 7000 rpm for 20 min, and filtering the resulting centrifuge through 0.45 um and 0.22 um filter membranes in turn to obtain a cell protein extract;
[0134] (4) Add a required amount of mannitol to the cell protein extract obtained in step (3), stir, mix evenly, and then freeze-dry. The resulting freeze-dried preparation contains 5% mannitol (m / m).
[0135] Test Example 1 Study on the therapeutic effect of the pharmaceutical composition of the present invention on facial paralysis associated with movement
[0136] Forty patients with associated movements of facial paralysis were selected and divided into group 1 (10 patients), group 2 (20 patients), and group 3 (10 patients). Patient inclusion criteria: meeting the diagnostic criteria of associated movements of traditional Chinese medicine and Western medicine, with onset of the disease for more than 6 months; age 20-70 years old; HB grade above grade II; informed consent to accept this trial; good compliance. Contraindications: complete rupture or loss of the facial nerve; infection or skin damage at the puncture site; local tumors or other space-occupying lesions involving the facial nerve; coagulation disorders, which may increase the risk of bleeding or hematoma; pacemaker implants, which may interfere with the normal operation of the pacemaker; pregnant or lactating women, which may affect the health of the fetus or baby; allergic to electrode needles or local anesthetics, which may cause allergic reactions or other adverse reactions; mental disorders or inability to cooperate with rehabilitation or corrective training treatment.
[0137] Treatment plan for Group 1 (each course of treatment is 7 days, and the treatment is for 4 courses): the drug composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, and 200mg of vitamin B1, which is prepared and used on the spot. The Yangbai, temple, Sibai, Yingxiang, Juliao, Dicang and Jiache points on the affected side of the face are selected for acupoint injection, and the acupoint injection is given once a day.
[0138] The treatment regimen of the two groups (each course of treatment was 7 days, and the treatment lasted for 4 courses) included pulsed radiofrequency surgery, postoperative oral medication and acupoint injection medication, and intraoperative and postoperative rehabilitation exercise training.
[0139] 1. Pulsed radiofrequency surgery: A radiofrequency temperature-controlled coagulator (model R-2000B M1, purchased from Beiqi Medical) was used to perform a micro-correction surgery on the lesion site for neural activation, repair and regulation based on long-term temperature-controlled high-voltage variable-frequency pulsed radiofrequency technology (pulse width 20ms, rest period 480ms, maximum voltage 100V, pulse frequency 2HZ). The pulsed radiofrequency was performed for 1200 seconds at 41-42°C, 90-140V, and 2-5Hz. During the surgery, two groups of facial exercises were performed, including keeping eyes open, repeatedly gritting teeth, and repeatedly blowing air.
[0140] 2. The scheme of simultaneous and / or sequential administration of oral medications after surgery:
[0141] After surgery, take methylcobalamin 0.5 mg / time, 4 times / day, every other month; adenosylcobalamin 0.5 mg / time, 3 times / day, for 3 consecutive weeks, stop for 1 week, and then continue to take for half a year;
[0142] 3. Postoperative acupuncture injection regimen:
[0143] The pharmaceutical composition for single acupuncture point injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride. It is prepared and used on the spot. The Yangbai point, temple, Sibai point, Yingxiang point, Juliao point, Dicang point and Jiache point on the affected side of the face are selected for acupuncture point injection. The acupuncture point injection is given once a day.
[0144] 4. Postoperative rehabilitation training:
[0145] The first set of rehabilitation exercises: one is to look in the mirror; the second is to slowly close your eyes, close your eyes for 5 seconds, then open your eyes and keep them open for 5 seconds, while controlling the corners of your mouth from lifting up, correcting the joint movements. Train three sets a day, 30 times each; the second set of rehabilitation exercises: one is to look in the mirror; the second is to open your eyes and try to keep the nerve branches silent; the third is to pout, show your teeth and puff your cheeks around your mouth. Train three sets a day, 10 times each.
[0146] The treatment regimen of the three groups (each course of treatment was 7 days, and the treatment lasted for 4 courses) included pulsed radiofrequency surgery, postoperative oral medication and acupoint injection medication, and intraoperative and postoperative rehabilitation exercise training.
[0147] 1. Pulsed radiofrequency surgery: A radiofrequency temperature-controlled coagulator (model R-2000B M1, purchased from Beiqi Medical) was used to perform a micro-correction surgery on the lesion site by nerve activation, repair and regulation based on long-term temperature-controlled high-voltage variable-frequency pulsed radiofrequency technology (pulse width 20ms, rest period 480ms, maximum voltage 100V, pulse frequency 2HZ). The pulsed radiofrequency was performed for 1200 seconds at 41-42°C, 90-140V, and 2-5Hz. During the surgery, two groups of facial exercises were performed, including keeping eyes open, repeatedly baring teeth, and repeatedly blowing air.
[0148] 2. The scheme of simultaneous and / or sequential administration of oral medications after surgery:
[0149] After surgery, take methylcobalamin 0.5 mg / time, 4 times / day, every other month; adenosylcobalamin 0.5 mg / time, 3 times / day, for 3 consecutive weeks, stop for 1 week, and then continue to take for half a year;
[0150] 3. Postoperative acupuncture injection regimen:
[0151] (1) The pharmaceutical composition for single acupuncture point injection is composed of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride. It is prepared and used on the spot. The Yangbai, Taiyang, Sibai, Yingxiang, Juliao, Dicang and Jiache points on the affected side of the face are selected for acupuncture point injection. The acupuncture point injection is once a day.
[0152] (2) Single acupoint injection: 130 μg of the freeze-dried preparation of the nerve repair cell protein extract prepared in Example 1 was dissolved in 2 ml of normal saline and injected into the Yangbai, Taiyang, Sibai, Yingxiang, Juliao, Dicang and Jiache points on the affected side of the face, the Taiyang and Dicang points on the opposite side, and the Hegu points on both hands. The injection was performed once a day.
[0153] 4. Postoperative rehabilitation training:
[0154] The first set of rehabilitation exercises: one is to look in the mirror; the second is to slowly close your eyes, close your eyes for 5 seconds, then open your eyes and keep them open for 5 seconds, while controlling the corners of your mouth from lifting up, correcting the joint movements. Train three sets a day, 30 times each; the second set of rehabilitation exercises: one is to look in the mirror; the second is to open your eyes and try to keep the nerve branches silent; the third is to pout, show your teeth and puff your cheeks around your mouth. Train three sets a day, 10 times each.
[0155] Efficacy evaluation: Satisfaction questionnaire and clinical scoring House-Brakmann facial nerve function grading efficacy evaluation form.
[0156]
[0157]
[0158] Group 1: Repeated treatment for 4-6 courses, more than 50% of patients had symptom improvement.
[0159] Group 2: Immediate effective rate was 70%, marked effective rate was 50%. Patient satisfaction after surgery was 80%. All patients had no side effects or adverse events. Repeat the treatment 2-3 times within 6 months, and the efficacy is cumulative.
[0160] Group 3: The patients' motor symptoms were significantly improved, with an immediate effective rate of 100% and a marked effective rate of 90%. The postoperative satisfaction rate was 100%. All the patients had no side effects, adverse events, or recurrence.
[0161] The above description of the specific embodiments of the present invention does not limit the present invention. Those skilled in the art may make various changes or modifications based on the present invention. As long as they do not depart from the spirit of the present invention, they should all fall within the scope of protection of the claims of the present invention.
Claims
1. A pharmaceutical composition for preventing and treating facial paralysis associated with movement, comprising a nerve repair cell protein extract having a repairing effect, and the remaining components are selected from a combination of mouse nerve growth factor, methylcobalamin, adenosylcobalamin, vitamin B1, dexamethasone, and lidocaine hydrochloride; a method for preparing the nerve repair cell protein extract, comprising the following steps: S-1: The density is 5.0×10 6 / mL-5.0×10 7 Mesenchymal stem cells (100 g / mL) were placed in a culture medium containing DMEM / F12 40-50%, RPMI1640 40-50%, bovine serum albumin 0.1-2%, epidermal growth factor 1-15 ug / mL, fibroblast growth factor 1-15 ug / mL, insulin transferrin 1-15 ug / mL, compound amino acid 18AA 0.01-0.1% and 2-10 μmol / L stressor, and then placed at 37.0°C ± 0.5°C, 5% ± 1.0% CO 2 After culturing for 2h-6h under the same conditions, the cells were separated, washed, and collected. in, The stressor is selected from the following compounds; ; S-2: Collect cells at a density of 5.0×10 6 / mL-5.0×10 7 pcs / mL is dispersed in a solvent, and then subjected to ultrasonic treatment at 2°C-8°C to obtain a cell lysate, wherein the solvent is selected from any one of physiological saline, 5% glucose solution, phosphate buffer, TBPS buffer, TBST buffer, Tris buffer or a combination thereof; S-3: After the cell lysate obtained in step S-2 is separated, the obtained separation solution is filtered through 0.45 um and 0.22 um filter membranes in sequence.
2. The pharmaceutical composition as claimed in claim 1, wherein the pharmaceutical composition for preventing and treating facial paralysis-associated movement consists of a pharmaceutical composition for single oral administration and a pharmaceutical composition for single acupoint injection.
3. The pharmaceutical composition according to claim 2, wherein a single dose of the pharmaceutical composition contains any one of 0.5-1.0 mg of methylcobalamin and 0.1-0.5 mg of adenosylcobalamin or a combination thereof.
4. The pharmaceutical composition according to claim 2, wherein the dosage regimen of the oral pharmaceutical composition is: oral administration of methylcobalamin 0.5 mg / time, 3-4 times / day, every other month; adenosylcobalamin 0.5 mg / time, 3 times / day, for 3 consecutive weeks, stop for 1 week, and then continue to repeat for half a year.
5. The pharmaceutical composition according to claim 2, wherein the oral pharmaceutical composition is selected from any one or a combination of simultaneous administration or sequential administration.
6. The pharmaceutical composition according to claim 2, wherein the pharmaceutical composition for single acupoint injection is a combination of 30 ug of mouse nerve growth factor, 0.5 mg of methylcobalamin, and 200 mg of vitamin B1.
7. The pharmaceutical composition according to claim 2, wherein the pharmaceutical composition for single acupoint injection contains any one of 30-90ug of mouse nerve growth factor, 0.5-1.0mg of methylcobalamin, 0.1-0.5mg of adenosylcobalamin, and 2-5mg of dexamethasone or a combination thereof.
8. The pharmaceutical composition as claimed in claim 2, wherein the pharmaceutical composition for single acupoint injection is any one of 30-90ug of mouse nerve growth factor, 0.5-1.0mg of methylcobalamin, 0.1-0.5mg of adenosylcobalamin, 2-5mg of dexamethasone, or 100-300mg of a nerve repair cell protein extract with repair efficacy or a combination thereof.
9. The pharmaceutical composition according to claim 2, wherein the pharmaceutical composition for single acupoint injection is composed of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 2mg of dexamethasone and 1ml of lidocaine hydrochloride, in, The concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.
10. The pharmaceutical composition according to claim 2, wherein the pharmaceutical composition for single acupoint injection is composed of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, in, The concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.
11. The pharmaceutical composition according to claim 2, wherein the pharmaceutical composition for single acupoint injection is composed of 90ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, in, The concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.
12. The pharmaceutical composition according to claim 2, wherein the pharmaceutical composition for single acupoint injection is composed of 60ug of mouse nerve growth factor, 0.8mg of methylcobalamin, 0.5mg of adenosylcobalamin, 3mg of dexamethasone and 1ml of lidocaine hydrochloride, in, The concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.
13. The pharmaceutical composition according to claim 2, wherein the pharmaceutical composition for single acupoint injection optionally contains 100-300 mg of any one or a combination of nerve repair cell protein extracts having repair efficacy.
14. The pharmaceutical composition according to claim 2, wherein the pharmaceutical composition for single acupoint injection is prepared and used immediately.
15. The pharmaceutical composition according to claim 2, wherein the Yangbai point, the Taiyang point, the Sibai point, the Yingxiang point, the Juliao point, the Dicang point and the Jiache point on the affected side of the face are selected for acupoint injection.
16. The pharmaceutical composition according to claim 2, wherein the pharmaceutical composition for single acupoint injection is injected into the acupoint once a day, and the course of treatment is 7 days.
17. The pharmaceutical composition according to claim 16, wherein each acupoint injection treatment lasts for 2-6 courses.
18. The pharmaceutical composition according to claim 17, wherein each acupoint injection treatment lasts for 4-5 courses.
19. The pharmaceutical composition according to any one of claims 1 to 18, wherein the pharmaceutical composition for preventing and treating facial paralysis-associated movement is optionally used in combination with any one of radiofrequency surgery and rehabilitation training exercises or a combination thereof.
20. The pharmaceutical composition according to claim 19, wherein the radiofrequency surgery is based on long-term temperature-controlled high-voltage variable-frequency pulse radiofrequency for 800 seconds to 1400 seconds under the conditions of 41°C-42°C, 90V-140V, and 2Hz-6Hz.
21. The pharmaceutical composition according to claim 20, wherein the radiofrequency surgery is based on long-term temperature-controlled high-voltage variable-frequency pulse radiofrequency for 960 seconds to 1200 seconds under the conditions of 41°C-42°C, 100V-120V, and 3Hz-5Hz.
22. The pharmaceutical composition according to claim 19, wherein the rehabilitation exercise training is selected from any one of the first set of rehabilitation exercise training, the second set of rehabilitation exercise training, or a combination thereof.
23. The pharmaceutical composition according to claim 22, wherein the first set of rehabilitation exercises comprises: first, looking in the mirror; second, slowly closing the eyes, closing the eyes for 5 seconds, and then opening the eyes for 5 seconds, while controlling the corners of the mouth to avoid upward movement and correcting the associated movements; the first set of rehabilitation exercises is performed three times a day, and each set is trained 30 times.
24. The pharmaceutical composition according to claim 22, wherein the second set of rehabilitation exercises comprises: first, looking in the mirror; second, opening eyes and keeping the nerve branches silent as much as possible; third, pursing lips, baring teeth and puffing cheeks around the mouth; and performing three sets of the first set of rehabilitation exercises every day, with each set of exercises performed 10 times.
25. The pharmaceutical composition according to any one of claims 1 to 18, wherein the treatment regimen for preventing and treating facial paralysis associated with movement is pulsed radiofrequency surgery, postoperative oral administration and acupoint injection, and intraoperative and postoperative rehabilitation training.
26. as claim 1-18 any one of described pharmaceutical composition, described facial paralysis is selected from any one or its combination in hemifacial spasm, facial paralysis / associated movement, trigeminal neuralgia, glossopharyngeal neuralgia, facial neuritis, peripheral facial paralysis, eye muscle spasm repair.
27. The pharmaceutical composition according to claim 1, wherein the culture medium in step S-1 contains DMEM / F12 42-45%, RPMI1640 42-45%, bovine serum albumin 0.5-1.5%, epidermal growth factor 5-10ug / mL, fibroblast growth factor 5-10ug / mL, insulin transferrin 5-10ug / mL, compound amino acid 18AA 0.02-0.05% and 3-8μmol / L of stressor.
28. The pharmaceutical composition according to claim 27, wherein the culture medium in step S-1 contains DMEM / F12 45%, RPMI1640 45%, bovine serum albumin 0.5%, epidermal growth factor 10ug / mL, fibroblast growth factor 10ug / mL, insulin transferrin 10ug / mL, compound amino acid 18AA 0.05% and 4-6μmol / L of stressor.
29. The pharmaceutical composition according to claim 1, wherein the density of mesenchymal stem cells in step S-1 is 8.0×10 6 -2.0×10 7 Pieces / mL.
30. The pharmaceutical composition according to claim 29, wherein the density of mesenchymal stem cells in step S-1 is 8.0×10 6 -1.0×10 7 Pieces / mL.
31. The pharmaceutical composition according to claim 1, wherein the mesenchymal stem cells in step S-1 are cultured in the culture medium for 3h-5h.
32. The pharmaceutical composition according to claim 31, wherein the mesenchymal stem cells in step S-1 are cultured in the culture medium for 3.5h-4.5h.
33. The pharmaceutical composition as claimed in claim 1, wherein the solvent for washing the cells in step S-1 is selected from any one of physiological saline, 5% glucose solution, phosphate buffer, TBPS buffer, TBST buffer, Tris buffer or a combination thereof, and the number of cell washing times is 2-5 times.
34. The pharmaceutical composition of claim 33, wherein the solvent for washing the cells in step S-1 is selected from any one of physiological saline, 5% glucose solution, phosphate buffer, TBPS buffer, TBST buffer, Tris buffer, or a combination thereof, and the cells are washed 3-4 times.
35. The pharmaceutical composition according to claim 1, wherein the separation in step S-1 is selected from any one of centrifugation and filtration or a combination thereof, in, The centrifugal condition is 1000-2000rpm*3-15min.
36. The pharmaceutical composition according to claim 35, wherein the separation in step S-1 is selected from any one of centrifugation and filtration or a combination thereof, in, The centrifugal condition is 1200rpm-1500rpm*5-10min.
37. The pharmaceutical composition according to claim 1, wherein the ultrasonic conditions of step S-2 are: working for 3s and then resting for 1s at 2°C-8°C, 25kHZ, 360W, and ultrasonic treatment for 1-5min.
38. The pharmaceutical composition according to claim 1, wherein the separation in step S-3 is selected from any one of 2000-8000 rpm*10-30 min centrifugation, multi-stage centrifugation, multi-stage filtration, or a combination thereof.
39. The pharmaceutical composition according to claim 38, wherein the separation in step S-3 is selected from any one of 3000-7000 rpm*15-25 min centrifugation, multi-stage centrifugation, and multi-stage filtration, or a combination thereof.
40. The pharmaceutical composition according to claim 39, wherein the multi-stage centrifugation in step S-3 is 3000-4000 rpm*3-5 min, 5000-6000 rpm*3-5 min and 7000 rpm*5-8 min, respectively.
41. The pharmaceutical composition of claim 38, wherein the pore size of the filter membrane of the multi-stage filtration is selected from any one of 80um, 50um, 30um, 10um, and 5um.
42. The pharmaceutical composition of claim 1, wherein the cell protein extract obtained in step S-3 is cryopreserved.
43. The pharmaceutical composition according to claim 42, wherein the cell protein extract obtained in step S-3 is frozen at -40°C to -20°C.
44. The pharmaceutical composition according to claim 1, wherein the cell protein extract obtained in step S-3 is hydrolyzed by either nuclease or omnipotent nuclease and then separated and purified.
45. The pharmaceutical composition according to claim 1, wherein the culture of the mesenchymal stem cells comprises the following steps: culturing the primary mesenchymal stem cells at an initial density of 5.0×10 5 -5.0×10 6 Add 100 μg / ml of culture medium to the culture medium, and then culture it at 37.0℃±0.5℃, 5%±1.0% CO2 for 10-15 days. Every 2-3 days, replace half of the culture medium after the culture medium turns yellow. in, The subculture medium contains DMEM / F12 medium containing 10% FBS, 100 U / ml penicillin and 100 ug / ml streptomycin.
46. The pharmaceutical composition of claim 45, wherein the culturing of primary mesenchymal stem cells comprises the following steps: 1) After cleaning and disinfecting the umbilical cord, dissect the tissue, take the Wharton's jelly tissue, and cut it into 3mm 3 The tissue blocks were collected by centrifugation, washing, and placed in DMEM / F12 medium containing 10% fetal bovine serum FBS, 100ug / ml penicillin, and 100ug / ml streptomycin, and then placed at 37.0℃±0.5℃, 5%±1.0%CO 2 Culture under the same conditions, replace half of the medium every 2-3 days, and culture until the tissue mass crawls out of the cells; 2) Shake and collect the lower layer cells, wash with PBS, add 0.25% trypsin to digest for 2 min-3 min, add an equal volume of trypsin stop solution to stop digestion, pipette gently, centrifuge at 1200-1500 rpm / min*5-8 min, and collect the cells.