WO2024051846A1 - Use of radio frequency apparatus in treatment of facial paralysis synkinesis - Google Patents

Use of radio frequency apparatus in treatment of facial paralysis synkinesis Download PDF

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Publication number
WO2024051846A1
WO2024051846A1 PCT/CN2023/117898 CN2023117898W WO2024051846A1 WO 2024051846 A1 WO2024051846 A1 WO 2024051846A1 CN 2023117898 W CN2023117898 W CN 2023117898W WO 2024051846 A1 WO2024051846 A1 WO 2024051846A1
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Prior art keywords
pharmaceutical composition
vitamin
facial paralysis
present
combination
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PCT/CN2023/117898
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French (fr)
Chinese (zh)
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陈琳
王宇
高文勇
李建军
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北京达尔文细胞生物科技有限公司
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Definitions

  • the invention belongs to the field of biomedicine, and specifically relates to the application of a radio frequency device in treating facial paralysis associated motion.
  • Facial paralysis is a complication of facial paralysis.
  • Common clinical associated motor symptoms include slight trembling of the upper lip on the affected side when the patient blinks; the eye on the affected side involuntarily closes when teeth are exposed; the frontalis muscle on the affected side contracts when trying to close the eyes; tears on the affected side occur when eating and chewing.
  • the proportion of moderate to severe peripheral facial paralysis combined with associated motion in the middle and late stages is as high as 60%-70%.
  • the associated motion of facial paralysis seriously affects the patient's self-confidence, work and life, and there is a lack of effective treatment methods.
  • New hypotheses on the pathogenesis of facial paralysis and associated motion include facial nerve scar repair, microfacial neuroma formation, facial nerve entropy increase, and neural pathways changing from order to disorder after facial nerve injury. So far, there are no drugs or treatment options that can be effectively used to treat facial paralysis and associated movements in clinical practice.
  • Radiofrequency technology is a minimally invasive interventional technology.
  • Continuous radiofrequency conventional radiofrequency, CRF
  • CRF pulsed radiofrequency
  • PRF pulsed radiofrequency
  • Radiofrequency thermocoagulation is an improved pain treatment technology.
  • the traditional PRF technology emits a radiofrequency current that lasts for 20 ms each time and then has an intermittent period of 480 ms, allowing the heat to have time to diffuse to the surrounding tissue.
  • the target temperature does not exceed 42°C, so it will not cause degeneration of local tissue.
  • Patent applications disclose technical content related to nerve repair protein extracts and nerve repair protein compositions with repair effects.
  • the aforementioned applications and contents are essential to this application. Few technical references and components.
  • the object of the present invention is to provide an application of a radio frequency device in treating associated movements of facial paralysis.
  • the radiofrequency surgery is performed under the conditions of 41°C-42°C, 90V-140V, 2Hz-6Hz, based on long-term temperature-controlled high-voltage variable frequency pulse radiofrequency for 800 seconds to 1400 seconds.
  • the radiofrequency surgery is performed under the conditions of 41°C-42°C, 100V-120V, 3Hz-5Hz, based on long-term temperature-controlled high-voltage variable frequency pulse radiofrequency for 960 seconds to 1200 seconds.
  • the radiofrequency surgery is optionally used in combination with any one of a pharmaceutical composition for preventing and treating associated movements of facial paralysis, rehabilitation training exercises, or a combination thereof.
  • the treatment plan for preventing and treating associated movements of facial paralysis includes pulse radiofrequency surgery, postoperative oral administration and acupoint injection administration, and intraoperative and postoperative rehabilitation exercise training.
  • the rehabilitation training exercises are facial paralysis rehabilitation training exercises originally created by the inventor (copyright registration number: Guozuodengzi-2022-I-10250228 and copyright registration number: Guozuodengzi-2022-F -10250229).
  • 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.
  • the first set of rehabilitation exercise training includes: first, looking in the mirror; second, slowly closing the eyes. After closing the eyes for 5 seconds, open the eyes and hold for 5 seconds. At the same time, the mouth and corners are controlled not to be raised together. Correct deviations and correct joint movements; train three groups of the first set of rehabilitation exercises every day, each group training 30 times.
  • the second set of rehabilitation exercise training includes: first, looking in the mirror; second, opening the eyes and keeping silent nerve branches as much as possible; third, pouting, gnashing teeth and puffing cheeks around the mouth; training the first set every day Perform three groups of rehabilitation exercises, each group training 10 times.
  • the facial paralysis is selected from any one of hemifacial spasm, facial paralysis/associated motion, trigeminal neuralgia, glossopharyngeal neuralgia, facial neuritis, peripheral facial paralysis, ophthalmospastic repair, or a combination thereof .
  • the pharmaceutical composition for preventing and treating associated movements of facial paralysis is selected from the group consisting of mouse nerve growth factor, monosialoganglioside (GM1), cerebrospinalis carnosine, methylcobalamin, and adenosine cobalt.
  • the pharmaceutical composition for preventing and treating associated movements of facial paralysis contains any one of mouse nerve growth factor, methylcobalamin, adenosine cobalt, or a combination thereof.
  • the pharmaceutical composition for preventing and treating associated movements of facial paralysis consists of a pharmaceutical composition for oral administration and a pharmaceutical composition for acupoint injection.
  • the pharmaceutical composition for single administration contains any one of 0.5-1.0 mg of methylcobalamin, 0.1-0.5 mg of adenosylcobalamin, or a combination thereof.
  • the dosage regimen of the oral pharmaceutical composition is: oral methylcobalamin 0.5 mg/time, 3-4 times/day, taken every other month; adenosylcobalamin 0.5 mg/time, 3 times/day days, 3 consecutive weeks, 1 week off, and then continue to repeat for half a year;
  • the oral pharmaceutical composition is selected from simultaneous administration or sequential administration or a combination thereof.
  • the pharmaceutical composition for a single acupoint injection is a combination of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, and 200mg of vitamin B1.
  • the pharmaceutical composition for single acupoint injection contains 30-90ug of mouse nerve growth factor, 0.5-1.0mg of methylcobalamin, 0.1-0.5mg of adenosylcobalamin, and 2-5mg of dexamethasone. any one or combination thereof.
  • the pharmaceutical composition for a single acupoint injection is mouse nerve growth factor 30-90ug, methylcobalamin 0.5-1.0mg, adenosylcobalamin 0.1-0.5mg, dexamethasone 2-5mg, 100-300 mg of any one or combination of nerve repair cell protein extracts and/or nerve repair protein compositions with repair effects.
  • 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%.
  • the pharmaceutical composition for a 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%.
  • the pharmaceutical composition for single acupoint injection is derived from mouse nerve It consists of 90ug of growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride.
  • the concentration of lidocaine hydrochloride is selected from 0.8%, 1%, 1.5% and 2%. any kind.
  • the pharmaceutical composition for a 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%.
  • the pharmaceutical composition for a single acupoint injection optionally contains 100-300 mg of any one of the nerve repair cell protein extract and/or the nerve repair protein composition with repair effect, or any other thereof. combination.
  • the pharmaceutical composition for single acupoint injection is used on an ad hoc basis.
  • the Yangbai point, temple point, Sibai point, Yingxiang point, Juliiao point, Dicang point and Jieche point on the affected side of the face are selected for acupoint injection.
  • the pharmaceutical composition for single acupoint injection is injected once a day into the acupoint, and the treatment course is 7 days.
  • each acupoint injection treatment lasts for 2-6 courses, preferably 4-5 courses.
  • Another object of the present invention is to provide a pharmaceutical composition for preventing and treating facial paralysis associated movements, which is selected from the group consisting of mouse nerve growth factor, monosialoganglioside (GM1), cerebrospinalis carnosine, methylcobalamin, and adenosine cobalt.
  • GM1 monosialoganglioside
  • cerebrospinalis carnosine methylcobalamin
  • adenosine cobalt a pharmaceutical composition for preventing and treating facial paralysis associated movements
  • the pharmaceutical composition for preventing and treating associated movements of facial paralysis contains any one of mouse nerve growth factor, methylcobalamin, adenosine cobalt, or a combination thereof.
  • the pharmaceutical composition for preventing and treating associated movements of facial paralysis consists of a pharmaceutical composition for oral administration and a pharmaceutical composition for acupoint injection.
  • the pharmaceutical composition for single administration contains any one of 0.5-1.0 mg of methylcobalamin, 0.1-0.5 mg of adenosylcobalamin, or a combination thereof.
  • the dosage regimen of the oral pharmaceutical composition is: oral methylcobalamin 0.5 mg/time, 3-4 times/day, taken every other month; adenosylcobalamin 0.5 mg/time, 3 times/day days, 3 consecutive weeks, 1 week off, and then continue to repeat for half a year;
  • the oral pharmaceutical composition is selected from simultaneous administration or sequential administration or a combination thereof.
  • the pharmaceutical composition for a single acupoint injection is a combination of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, and 200mg of vitamin B1.
  • the pharmaceutical composition for single acupoint injection contains 30-90ug of mouse nerve growth factor, 0.5-1.0mg of methylcobalamin, 0.1-0.5mg of adenosylcobalamin, and 2-5mg of dexamethasone. any one or combination thereof.
  • the pharmaceutical composition for a single acupoint injection is mouse nerve growth factor 30-90ug, methylcobalamin 0.5-1.0mg, adenosylcobalamin 0.1-0.5mg, dexamethasone 2-5mg, 100-300 mg of any one or combination of nerve repair cell protein extracts and/or nerve repair protein compositions with repair effects.
  • 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%.
  • the pharmaceutical composition for a 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%.
  • the pharmaceutical composition for a 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 Composition, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.
  • the pharmaceutical composition for a 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%.
  • the pharmaceutical composition for a single acupoint injection optionally contains 100-300 mg of any one of the nerve repair cell protein extract and/or the nerve repair protein composition with repair effect, or any other thereof. combination.
  • the pharmaceutical composition for single acupoint injection is used on an ad hoc basis.
  • the Yangbai point, temple point, Sibai point, Yingxiang point, Juliiao point, Dicang point and Jieche point on the affected side of the face are selected for acupoint injection.
  • the pharmaceutical composition for single acupoint injection is injected once a day into the acupoint, and the treatment course is 7 days.
  • each acupoint injection treatment lasts for 2-6 courses, preferably 4-5 courses.
  • the pharmaceutical composition for preventing and treating associated movements of facial paralysis is optionally used in combination with any one of radiofrequency surgery, rehabilitation training exercises, or a combination thereof.
  • the radiofrequency surgery is performed under the conditions of 41°C-42°C, 90V-140V, 2Hz-6Hz, based on long-term temperature-controlled high-voltage variable frequency pulse radiofrequency for 800 seconds to 1400 seconds.
  • the radiofrequency surgery is performed under the conditions of 41°C-42°C, 100V-120V, 3Hz-5Hz, based on long-term temperature-controlled high-voltage variable frequency pulse radiofrequency for 960 seconds to 1200 seconds.
  • the rehabilitation training exercises are facial paralysis rehabilitation training exercises originally created by the inventor (copyright registration number: Guozuodengzi-2022-I-10250228 and copyright registration number: Guozuodengzi-2022-F -10250229).
  • 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.
  • the first set of rehabilitation exercise training includes: first, looking in the mirror; second, slowly closing the eyes. After closing the eyes for 5 seconds, open the eyes and hold for 5 seconds. At the same time, the mouth and corners are controlled not to be raised together. Correct deviations and correct joint movements; train three groups of the first set of rehabilitation exercises every day, each group training 30 times.
  • the second set of rehabilitation exercise training includes: first, looking in the mirror; second, opening the eyes and keeping silent nerve branches as much as possible; third, pouting, gnashing teeth and puffing cheeks around the mouth; training the first set every day Perform three groups of rehabilitation exercises, each group training 10 times.
  • the treatment plan for preventing and treating facial nerve paralysis in the recovery period includes pulsed radiofrequency surgery, postoperative oral administration and acupoint injection administration, and intraoperative and postoperative rehabilitation exercise training.
  • the facial nerve paralysis is selected from any one of hemifacial spasm, facial paralysis/joint movement, trigeminal neuralgia, glossopharyngeal neuralgia, facial neuritis, peripheral facial paralysis, ophthalmospastic repair, or their combinations. combination.
  • Another object of the present invention is to provide a treatment plan for preventing and treating associated movements of facial paralysis.
  • the treatment plan includes a pharmaceutical composition for preventing and treating associated movements of facial paralysis, optionally combined with any one of radiofrequency surgery, rehabilitation training exercises, or a combination thereof. Used in combination.
  • the pharmaceutical composition for preventing and treating associated movements of facial paralysis is selected from the group consisting of mouse nerve growth factor, monosialoganglioside (GM1), cerebrospinalis carnosine, methylcobalamin, and adenosine cobalt.
  • mouse nerve growth factor monosialoganglioside (GM1)
  • cerebrospinalis carnosine methylcobalamin
  • adenosine cobalt adenosine cobalt.
  • the pharmaceutical composition for preventing and treating associated movements of facial paralysis contains any one of mouse nerve growth factor, methylcobalamin, adenosine cobalt, or a combination thereof.
  • the pharmaceutical composition for preventing and treating associated movements of facial paralysis consists of a pharmaceutical composition for oral administration and a pharmaceutical composition for acupoint injection.
  • the pharmaceutical composition for single administration contains any one of 0.5-1.0 mg of methylcobalamin, 0.1-0.5 mg of adenosylcobalamin, or a combination thereof.
  • the dosage regimen of the oral pharmaceutical composition is: oral methylcobalamin 0.5 mg/time, 3-4 times/day, taken every other month; adenosylcobalamin 0.5 mg/time, 3 times/day days, 3 consecutive weeks, 1 week off, and then continue to repeat for half a year;
  • the oral pharmaceutical composition is selected from simultaneous administration or sequential administration or a combination thereof.
  • the pharmaceutical composition for a single acupoint injection is a combination of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, and 200mg of vitamin B1.
  • the pharmaceutical composition for single acupoint injection contains 30-90ug of mouse nerve growth factor, 0.5-1.0mg of methylcobalamin, 0.1-0.5mg of adenosylcobalamin, and 2-5mg of dexamethasone. any one or combination thereof.
  • the pharmaceutical composition for a single acupoint injection is mouse nerve growth factor 30-90ug, methylcobalamin 0.5-1.0mg, adenosylcobalamin 0.1-0.5mg, dexamethasone 2-5mg, 100-300mg tool Any one or combination of nerve repair cell protein extracts and/or nerve repair protein compositions with repair effects.
  • 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%.
  • the pharmaceutical composition for a 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%.
  • the pharmaceutical composition for a 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 Composition, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.
  • the pharmaceutical composition for a 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%.
  • the pharmaceutical composition for a single acupoint injection optionally contains 100-300 mg of any one of the nerve repair cell protein extract and/or the nerve repair protein composition with repair effect, or any other thereof. combination.
  • the pharmaceutical composition for single acupoint injection is used on an ad hoc basis.
  • the Yangbai point, temple point, Sibai point, Yingxiang point, Juliiao point, Dicang point and Jieche point on the affected side of the face are selected for acupoint injection.
  • the pharmaceutical composition for single acupoint injection is injected once a day into the acupoint, and the treatment course is 7 days.
  • each acupoint injection treatment lasts for 2-6 courses, preferably 4-5 courses.
  • the pharmaceutical composition for preventing and treating associated movements of facial paralysis is optionally used in combination with any one of radiofrequency surgery, rehabilitation training exercises, or a combination thereof.
  • the radiofrequency surgery is performed under the conditions of 41°C-42°C, 90V-140V, 2Hz-6Hz, based on long-term temperature-controlled high-voltage variable frequency pulse radiofrequency for 800 seconds to 1400 seconds.
  • the radiofrequency surgery operates at 41°C-42°C, 100V-120V, 3Hz- Under the condition of 5Hz, based on long-term temperature control high voltage variable frequency pulse radio frequency 960 seconds-1200 seconds.
  • the rehabilitation training exercises are facial paralysis rehabilitation training exercises originally created by the inventor (copyright registration number: Guozuodengzi-2022-I-10250228 and copyright registration number: Guozuodengzi-2022-F -10250229).
  • 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.
  • the first set of rehabilitation exercise training includes: first, looking in the mirror; second, slowly closing the eyes. After closing the eyes for 5 seconds, open the eyes and hold for 5 seconds. At the same time, the mouth and corners are controlled not to be raised together. Correct deviations and correct joint movements; train three groups of the first set of rehabilitation exercises every day, each group training 30 times.
  • the second set of rehabilitation exercise training includes: first, looking in the mirror; second, opening the eyes and keeping silent nerve branches as much as possible; third, pouting, gnashing teeth and puffing cheeks around the mouth; training the first set every day Perform three groups of rehabilitation exercises, each group training 10 times.
  • the treatment plan for preventing and treating facial nerve paralysis in the recovery period includes pulsed radiofrequency surgery, postoperative oral administration and acupoint injection administration, and intraoperative and postoperative rehabilitation exercise training.
  • the facial nerve paralysis is selected from any one of hemifacial spasm, facial paralysis/joint movement, trigeminal neuralgia, glossopharyngeal neuralgia, facial neuritis, peripheral facial paralysis, ophthalmospastic repair, or their combinations. combination.
  • the nerve repair cell protein extract or nerve repair cell protein composition with repair effect described in the present invention is prepared with reference to patent applications (CN2023100429139, PCT/CN2023/073566, CN2023100429143, PCT/CN2023/073582). have to.
  • the preparation method of the nerve repair cell protein extract with nerve repair effect includes the following steps:
  • S-1 Mesenchymal passaged stem cells with a density of 5.0 ⁇ 10 6 /mL-5.0 ⁇ 10 7 /mL were placed in DMEM/F12 40-50%, RPMI1640 40-50%, bovine serum albumin (BSA) )0.1-2%, epidermal growth factor (EGF) 1-15ug/mL, fibroblast growth factor (FGF) 1-15ug/mL, insulin transferrin 1-15ug/mL, compound amino acid (18AA) 0.01- 0.1% and 2-10 ⁇ mol/L stress medium, and then culture it at 37.0°C ⁇ 0.5°C, 5% ⁇ 1.0% CO2 for 2h-6h, separate, wash, and collect the cells, where , the stressor is selected from any one of compounds 1-16 or a combination thereof;
  • BSA bovine serum albumin
  • S-2 Disperse the collected cells in the solvent at a density of 5.0 ⁇ 10 6 /mL-5.0 ⁇ 10 7 /mL, and then place them at 2°C-8°C for ultrasonic treatment to prepare a cell lysis solution , wherein the solvent is selected from any one selected from physiological saline, 5% glucose solution, phosphate buffered saline (PBS), TBPS buffer, TBST buffer, Tris buffer or a combination thereof;
  • PBS phosphate buffered saline
  • TBPS buffer TBST buffer
  • Tris buffer Tris buffer
  • step S-3 After separating the cell lysate prepared in step S-2, the obtained separation liquid is filtered through 0.45um and 0.22um filters in sequence.
  • the culture medium of step S-1 contains DMEM/F12 42-45%, RPMI1640 42-45%, bovine serum albumin (BSA) 0.5-1.5%, epidermal cell 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 3-8 ⁇ mol/L stressors.
  • BSA bovine serum albumin
  • the culture medium of step S-1 contains DMEM/F12 45%, RPMI1640 45%, bovine serum albumin (BSA) 0.5%, epidermal growth factor (EGF) 10ug/mL, fibroblasts Growth factor (FGF) 10ug/mL, insulin transferrin 10ug/mL, compound amino acid (18AA) 0.05% and 4-6 ⁇ mol/L stressors.
  • BSA bovine serum albumin
  • the density of mesenchymal passage stem cells in step S-1 is 8.0 ⁇ 10 6 -2.0 ⁇ 10 7 cells/mL, preferably 8.0 ⁇ 10 6 -1.0 ⁇ 10 7 cells/mL.
  • the mesenchymal passage stem cells in step S-1 are cultured in the culture medium for 3h-5h, preferably 3.5h-4.5h.
  • the solvent for washing cells in step S-1 is selected from any one of physiological saline, 5% glucose solution, phosphate buffer (PBS), TBPS buffer, TBST buffer, and Tris buffer. Or a combination thereof, the number of cell washings is 2-5 times, preferably 3-4 times.
  • the separation described in step S-1 is selected from any one of centrifugation, filtration or a combination thereof, wherein the centrifugation conditions are 1000-2000rpm*3-15min, preferably 1200rpm-1500rpm* 5-10min.
  • the ultrasonic conditions of step S-2 are: working at 2°C-8°C, 25kHZ, 360W for 3 seconds, followed by a gap of 1 second, and ultrasonic treatment for 1-5 minutes.
  • the separation described 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 .
  • the multi-stage centrifugation in step S-3 is 3000-4000rpm*3-5min, 5000-6000rpm*3-5min and 7000rpm*5-8min.
  • the filter membrane pore size of the multi-stage filtration is selected from any one of 80um, 50um, 30um, 10um, and 5um.
  • the cell protein extract prepared in step S-3 is frozen and stored, preferably at -40°C to -20°C.
  • the cell protein extract prepared in step S-3 is enzymatically hydrolyzed by either a nuclease or a totipotent nuclease and then separated and purified.
  • the culture of mesenchymal passaged stem cells or the culture of primary mesenchymal stem cells adopts the culture methods in this field.
  • the culture of mesenchymal passage stem cells includes the following steps: adding primary mesenchymal stem cells to the passage medium at an initial density of 5.0 ⁇ 10 5 -5.0 ⁇ 10 6 /ml. , and then place it in the culture medium at 37.0°C ⁇ 0.5°C and 5% ⁇ 1.0% CO2 for 10-15 days. Every 2-3 days, after observing that the subculture medium turns yellow, replace half of the subculture medium. , the subculture medium contains DMEM/F12 medium with 10% FBS, 100 U/ml penicillin and 100ug/ml streptomycin.
  • the culture of primary mesenchymal stem cells includes the following steps:
  • the percentage when the present invention relates to the percentage between liquid and liquid, the percentage is volume/volume percentage; when the present invention relates to the percentage between liquid and solid, the percentage is volume/weight percentage; the present invention When referring to percentages between solids and liquids, the percentages are weight/volume; the remainder are weight/weight.
  • Acupoint selection Position the acupoints in accordance with the National Standard of the People's Republic of China "Acupoint Names and Positioning" (GB/T 12345-2006) issued by the State Bureau of Technical Supervision.
  • the present invention has the following beneficial effects:
  • the present invention adopts radio frequency method for the treatment of joint movement of facial paralysis, which does not require open surgery and avoids the trauma and pain of traditional treatment.
  • the pharmaceutical composition for treating joint movement each component synergizes and the pharmaceutical composition takes effect. It has fast, prolonged action and good therapeutic effect. It can reduce the side effects caused by the use of a single drug and accelerate the improvement of facial paralysis symptoms.
  • the treatment is safe and reliable, without obvious side effects and complications.
  • the present invention can save the amount of medicine used, significantly reduce production costs, is easy to operate, and is suitable for large-scale industrial production.
  • the culture of primary mesenchymal stem cells includes the following steps:
  • tissue blocks Shake gently to make the tissue blocks fall, and collect the tissue blocks and low-layer cells respectively. Among them, the collected The tissue block is re-attached and cultured;
  • Passage culture of primary mesenchymal stem cells (culture of mesenchymal stem cells): Add primary mesenchymal stem cells at an initial density of 5.0 ⁇ 10 5 -5.0 ⁇ 10 6 /ml into a solution containing 10% FBS and 100U /ml penicillin and 100ug/ml streptomycin in DMEM/F12 culture medium, and then culture it at 37.0°C ⁇ 0.5°C, 5% ⁇ 1.0% CO2 for 10-15 days, with an interval of 2-3 days , after observing that the medium turns yellow, replace the medium by half.
  • step (2) Disperse the cells collected in step (1) in physiological saline at a density of 1.0 ⁇ 10 7 cells/mL, ultrasonicate for 3s, 1s gap, and 2min under the conditions of 2-8°C, 25kHz, 360W to obtain cells. Lysis solution;
  • step (3) Centrifuge the cell lysate prepared in step (2) at 7000rpm*20min, and filter the obtained centrifuge through 0.45um and 0.22um filters in sequence to obtain the cell protein extract;
  • step (3) Add the required amount of mannitol to the cell protein extract prepared in step (3), stir, mix evenly, and freeze-dry.
  • the resulting freeze-dried preparation contains 5% mannitol (m/m).
  • Test Example 1 Study on the therapeutic effect of the pharmaceutical composition of the present invention on facial paralysis and associated movements
  • Group 1 Forty patients with facial paralysis and associated motion were selected and divided into Group 1 (10 patients), Group 2 (20 patients), and Group 3 (10 patients). name).
  • Patient inclusion criteria meet the diagnostic criteria of joint sports traditional Chinese medicine and Western medicine, the patient has been ill for more than 6 months; age is 20-70 years old; HB grade is above level II; informed consent to accept this trial; good compliance.
  • Contraindications Patients with complete rupture or loss of the facial nerve; infection or skin damage at the puncture site; patients with local tumors or other space-occupying lesions involving the facial nerve; patients with coagulation dysfunction, which may increase the risk of bleeding or hematoma; pacemaker implantation Those who are allergic may interfere with the normal work of the pacemaker; those who are pregnant or lactating may affect the health of the fetus or baby; those who are allergic to electrode needles or local anesthetics may cause allergic reactions or other adverse reactions; those who are mentally disordered or unable to cooperate Rehabilitation or corrective training therapist.
  • the pharmaceutical composition for a single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, and 200mg of vitamin B1.
  • Acupoint injections are performed at the Yangbai point, temple point, Sibai point, Yingxiang point, Juliiao point, Dicang point and Jieche point on the affected side of the face, once a day.
  • the treatment plan for the 2 groups includes pulsed radiofrequency surgery, postoperative oral administration and acupoint injection administration, as well as intraoperative and postoperative rehabilitation exercise training.
  • Pulsed radiofrequency surgery Using a radiofrequency temperature-controlled coagulator (model R-2000B M1, purchased from Beiqi Medical), based on long-term temperature-controlled high-voltage variable frequency pulsed radiofrequency technology, nerve activation, repair, regulation and micro-correction surgery are performed on the lesion. (Pulse width 20ms, resting period 480ms, maximum voltage value 100V, pulse frequency 2HZ), pulse radio frequency for 1200 seconds under the conditions of 41-42°C, 90-140V, 2-5Hz; during the operation, two groups of eyes were kept open , facial movements that repeatedly show teeth and puff;
  • the pharmaceutical composition for a 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.
  • Acupoint injection is performed at Yangbai point, Taiyang point, Sibai point, Yingxiang point, Juliiao point, Dicang point and Jieche point, once a day.
  • the first set of rehabilitation exercises first, look in the mirror; second, slowly close your eyes. After closing your eyes for 5 seconds, open your eyes and hold them for 5 seconds. At the same time, you should control the mouth and corners to avoid joint lifting movements, and correct deviations and joint movements. Train three groups every day, each group trains Practice 30 times; the second set of rehabilitation exercises: first, look in the mirror; second, open your eyes and try to keep the nerve branches as silent as possible; third, pout, clenched teeth and puffed cheeks around the mouth. Train three groups a day, each group training 10 times.
  • the treatment plan of the 3 groups includes pulsed radiofrequency surgery, postoperative oral administration and acupoint injection administration, as well as intraoperative and postoperative rehabilitation exercise training.
  • Pulsed radiofrequency surgery Using a radiofrequency temperature-controlled coagulator (model R-2000B M1, purchased from Beiqi Medical), based on long-term temperature-controlled high-voltage variable frequency pulsed radiofrequency technology, nerve activation, repair, regulation and micro-correction surgery are performed on the lesion. (Pulse width 20ms, resting period 480ms, maximum voltage value 100V, pulse frequency 2HZ), pulse radio frequency for 1200 seconds under the conditions of 41-42°C, 90-140V, 2-5Hz; during the operation, two groups of eyes were kept open , facial movements that repeatedly show teeth and puff;
  • the pharmaceutical composition for a 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.
  • Acupoint injections are performed at the Yangbai point, temple point, Sibai point, Yingxiang point, Juliiao point, Dicang point and Jieche point on the side face, once a day.
  • the first set of rehabilitation exercises first, look in the mirror; second, slowly close your eyes. After closing your eyes for 5 seconds, open your eyes and hold them for 5 seconds. At the same time, you should control the mouth and corners to avoid joint lifting movements, and correct deviations and joint movements.
  • Three groups are trained every day, each group is trained 30 times; the second set of rehabilitation exercises: the first is to look in the mirror; the second is to open the eyes and try to keep the silent nerve branches; the third is to pout, gnash the teeth and puff out the cheeks around the mouth. Train three groups a day, each group training 10 times.
  • Group 1 Repeated treatment for 4-6 courses, more than 50% of patients' symptoms improved.
  • Group 3 The patients' associated motor symptoms were significantly improved, with an immediate effective rate of 100% and a significant efficiency of 90%. Postoperative patient satisfaction was 100%. All tested patients had no side effects, adverse events, or recurrence.

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Abstract

The present invention relates to use of a radio frequency apparatus in the treatment of facial paralysis synkinesis. The radio frequency conditions are as follows: the temperature is 41-42 °C, the voltage is 90-140 V, the frequency is 2-6 Hz, and the time is 960-1200 seconds. The present invention further relates to a pharmaceutical composition for preventing and treating facial paralysis synkinesis and combined use thereof with radio frequency surgery and rehabilitation training. By means of a synergistic effect, the pharmaceutical composition takes effect quickly, has a prolonged duration of action, and has a good treatment effect on facial paralysis synkinesis.

Description

射频装置在治疗面瘫连带运动中的应用Application of radiofrequency devices in the treatment of facial paralysis and associated movements 技术领域Technical field
本发明属于生物医药领域，具体涉及一种射频装置在治疗面瘫连带运动的应用。The invention belongs to the field of biomedicine, and specifically relates to the application of a radio frequency device in treating facial paralysis associated motion.
背景技术Background technique
面瘫连带运动是面瘫并发症的一种。临床常见的连带运动症状包括病人瞬目时，即发生病侧上唇轻微颤动；露齿时，病侧眼睛不自主闭合；试图闭目时，病侧额肌收缩；进食咀嚼时，病侧流泪，伴颞部皮肤潮红、局部发热等。中重度周围性面瘫中晚期合并连带运动的比例高达60％-70％，面瘫连带运动严重影响了患者的自信、工作和生活，且缺乏有效的治疗手段。面瘫连带运动的发病机制新假说包括面神经损伤后，面神经瘢痕修复，微小面神经瘤形成、面神经增熵值，神经通路从有序到无序。迄今，临床尚没有能够有效用于治疗面瘫连带运动的药物和治疗方案。Facial paralysis is a complication of facial paralysis. Common clinical associated motor symptoms include slight trembling of the upper lip on the affected side when the patient blinks; the eye on the affected side involuntarily closes when teeth are exposed; the frontalis muscle on the affected side contracts when trying to close the eyes; tears on the affected side occur when eating and chewing. Accompanied by temporal skin flushing and local heating. The proportion of moderate to severe peripheral facial paralysis combined with associated motion in the middle and late stages is as high as 60%-70%. The associated motion of facial paralysis seriously affects the patient's self-confidence, work and life, and there is a lack of effective treatment methods. New hypotheses on the pathogenesis of facial paralysis and associated motion include facial nerve scar repair, microfacial neuroma formation, facial nerve entropy increase, and neural pathways changing from order to disorder after facial nerve injury. So far, there are no drugs or treatment options that can be effectively used to treat facial paralysis and associated movements in clinical practice.
射频技术为微创介入技术。连续射频(conventional radiofrequency,CRF)易引起组织蛋白变性，破坏神经、阻止疼痛信号的传导破坏靶组织等副作用。脉冲射频(pulsed radiofrequency,PRF)的射频能量足以增加射频场效应而不引起组织损伤，是一种安全、有效的治疗疼痛的方法。射频热凝为改进的疼痛治疗技术。传统的PRF技术每次发出的射频电流持续20ms后有480ms间歇期，使热量有时间向周围组织扩散，靶点温度不超过42℃，故不会导致局部组织的变性。调节神经功能，不产生神经组织损伤，不阻断神经传导；利用高电压、脉冲式电流，产生电压波动，间歇期使射频电流在神经组织附近产生的热量扩散，保证尖端温度不超过42℃，不会导致局部组织的变性；Kapural研究表明，同单极射频相比，双极射频能够产生更广阔的作用范围。Radiofrequency technology is a minimally invasive interventional technology. Continuous radiofrequency (conventional radiofrequency, CRF) can easily cause side effects such as tissue protein denaturation, damage to nerves, blocking the transmission of pain signals and damaging target tissues. The radiofrequency energy of pulsed radiofrequency (PRF) is sufficient to increase the radiofrequency field effect without causing tissue damage. It is a safe and effective method for treating pain. Radiofrequency thermocoagulation is an improved pain treatment technology. The traditional PRF technology emits a radiofrequency current that lasts for 20 ms each time and then has an intermittent period of 480 ms, allowing the heat to have time to diffuse to the surrounding tissue. The target temperature does not exceed 42°C, so it will not cause degeneration of local tissue. Regulates nerve function without causing damage to nerve tissue or blocking nerve conduction; it uses high voltage and pulsed current to generate voltage fluctuations. During the intermittent period, the heat generated by the radiofrequency current near the nerve tissue is diffused to ensure that the tip temperature does not exceed 42°C. It will not cause degeneration of local tissue; Kapural research shows that compared with unipolar radiofrequency, bipolar radiofrequency can produce a wider range of action.
专利申请(CN2023100429139、PCT/CN2023/073566、CN2023100429143、PCT/CN2023/073582)公开了有关具有修复功效的神经修复蛋白提取物及神经修复蛋白组合物的技术内容，前述申请及内容作为本申请必不可少的技术参考和组成部分。 Patent applications (CN2023100429139, PCT/CN2023/073566, CN2023100429143, PCT/CN2023/073582) disclose technical content related to nerve repair protein extracts and nerve repair protein compositions with repair effects. The aforementioned applications and contents are essential to this application. Few technical references and components.
发明内容Contents of the invention
本发明的目的在于提供一种射频装置在治疗面瘫连带运动中的应用。The object of the present invention is to provide an application of a radio frequency device in treating associated movements of facial paralysis.
本发明的优选技术方案中，所述射频手术在41℃-42℃、90V-140V、2Hz-6Hz条件下，基于长时程温控高电压变频脉冲射频800秒-1400秒。In the preferred technical solution of the present invention, the radiofrequency surgery is performed under the conditions of 41°C-42°C, 90V-140V, 2Hz-6Hz, based on long-term temperature-controlled high-voltage variable frequency pulse radiofrequency for 800 seconds to 1400 seconds.
本发明的优选技术方案中，所述射频手术在41℃-42℃、100V-120V、3Hz-5Hz条件下，基于长时程温控高电压变频脉冲射频960秒-1200秒。In the preferred technical solution of the present invention, the radiofrequency surgery is performed under the conditions of 41°C-42°C, 100V-120V, 3Hz-5Hz, based on long-term temperature-controlled high-voltage variable frequency pulse radiofrequency for 960 seconds to 1200 seconds.
本发明的优选技术方案中，所述射频手术任选地与用于防治面瘫连带运动的药物组合物、康复训练操的任一种或其组合联合使用。In the preferred technical solution of the present invention, the radiofrequency surgery is optionally used in combination with any one of a pharmaceutical composition for preventing and treating associated movements of facial paralysis, rehabilitation training exercises, or a combination thereof.
本发明的优选技术方案中，所述防治面瘫连带运动的治疗方案为，脉冲射频手术、术后口服给药和穴位注射给药以及术中和术后康复操训练。In the preferred technical solution of the present invention, the treatment plan for preventing and treating associated movements of facial paralysis includes pulse radiofrequency surgery, postoperative oral administration and acupoint injection administration, and intraoperative and postoperative rehabilitation exercise training.
本发明的优选技术方案中，所述康复训练操为发明人独创的面瘫康复训练操(著作权登记号：国作登字-2022-I-10250228和著作权登记号：国作登字-2022-F-10250229)。In the preferred technical solution of the present invention, the rehabilitation training exercises are facial paralysis rehabilitation training exercises originally created by the inventor (copyright registration number: Guozuodengzi-2022-I-10250228 and copyright registration number: Guozuodengzi-2022-F -10250229).
本发明的优选技术方案中，所述的康复操训练选自第一套康复操训练、第二套康复操训练的任一种或其组合。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, the second set of rehabilitation exercise training, or a combination thereof.
本发明的优选技术方案中，第一套康复操训练包括，一是照镜子；二是慢闭眼，闭眼5秒后，睁开眼保持5秒，同时控制不出现口角连带上提动作，纠偏纠正连带运动；每天训练第一套康复操三组，每组训练30遍。In the preferred technical solution of the present invention, the first set of rehabilitation exercise training includes: first, looking in the mirror; second, slowly closing the eyes. After closing the eyes for 5 seconds, open the eyes and hold for 5 seconds. At the same time, the mouth and corners are controlled not to be raised together. Correct deviations and correct joint movements; train three groups of the first set of rehabilitation exercises every day, each group training 30 times.
本发明的优选技术方案中，第二套康复操训练包括，一是照镜子；二是睁眼，尽量保持静默神经分支；三是口周噘嘴、呲牙和鼓腮；每天训练第一套康复操三组，每组训练10遍。In the preferred technical solution of the present invention, the second set of rehabilitation exercise training includes: first, looking in the mirror; second, opening the eyes and keeping silent nerve branches as much as possible; third, pouting, gnashing teeth and puffing cheeks around the mouth; training the first set every day Perform three groups of rehabilitation exercises, each group training 10 times.
本发明的优选技术方案中，所述面瘫选自面肌痉挛、面瘫/连带运动、三叉神经痛、舌咽神经痛、面神经炎、周围性面瘫、眼肌痉挛修复中的任一种或其组合。In the preferred technical solution of the present invention, the facial paralysis is selected from any one of hemifacial spasm, facial paralysis/associated motion, trigeminal neuralgia, glossopharyngeal neuralgia, facial neuritis, peripheral facial paralysis, ophthalmospastic repair, or a combination thereof .
本发明的优选技术方案中，所述用于防治面瘫连带运动的药物组合物，选自鼠神经生长因子、单唾液酸神经节苷脂(GM1)、脑苷肌肽、甲钴胺、腺苷钴胺、复合维生素B、丁苯酞、马来酸桂哌齐特、依达拉奉、依达拉奉右莰醇、胞磷胆碱、胞磷胆碱钠、神经节苷脂、奥拉西坦、脑蛋白、吡拉西坦、神经生长因子、胞二磷胆碱、神经妥乐平、谷维素、维生素B1、维生素B6、维生素B12、维生素 C、维生素E、复方脑肽节苷脂、茴拉西坦、神经酸、具有修复功效的神经修复细胞蛋白提取物或神经修复蛋白组合物的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating associated movements of facial paralysis is selected from the group consisting of mouse nerve growth factor, monosialoganglioside (GM1), cerebrospinalis carnosine, methylcobalamin, and adenosine cobalt. Amines, vitamin B complex, butylphthalide, cinpazide maleate, edaravone, edaravone dexbornillol, citicoline, citicoline sodium, gangliosides, olaxidine Tan, cerebroprotein, piracetam, nerve growth factor, citicoline, neurotropin, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamin C. Any one or a combination of vitamin E, compound cerebroside, aniracetam, nervonic acid, nerve repair cell protein extract with repair effect or nerve repair protein composition.
本发明的优选技术方案中，所述防治面瘫连带运动的药物组合物含有鼠神经生长因子、甲钴胺、腺苷钴的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating associated movements of facial paralysis contains any one of mouse nerve growth factor, methylcobalamin, adenosine cobalt, or a combination thereof.
本发明的优选技术方案中，所述用于防治面瘫连带运动的药物组合物由单次口服用的药物组合物和单次穴位注射用的药物组合物组成。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating associated movements of facial paralysis consists of a pharmaceutical composition for oral administration and a pharmaceutical composition for acupoint injection.
本发明的优选技术方案中，单次给药的药物组合物含有甲钴胺0.5-1.0mg、腺苷钴胺0.1-0.5mg的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for single administration contains any one of 0.5-1.0 mg of methylcobalamin, 0.1-0.5 mg of adenosylcobalamin, or a combination thereof.
本发明的优选技术方案中，口服用药物组合物的给药方案为：口服甲钴胺0.5mg/次，3-4次/天，隔月服用；腺苷钴胺0.5mg/次，3次/天，连续3周，停1周，然后继续重复半年；In the preferred technical solution of the present invention, the dosage regimen of the oral pharmaceutical composition is: oral methylcobalamin 0.5 mg/time, 3-4 times/day, taken every other month; adenosylcobalamin 0.5 mg/time, 3 times/day days, 3 consecutive weeks, 1 week off, and then continue to repeat for half a year;
本发明的优选技术方案中，所述口服用药物组合物选自同时给药或序贯给药的任一种或其组合。In a preferred technical solution of the present invention, the oral pharmaceutical composition is selected from simultaneous administration or sequential administration or a combination thereof.
本发明的优选技术方案中，单次穴位注射用的药物组合物为鼠神经生长因子30ug、甲钴胺0.5mg、维生素B1 200mg的组合。In the preferred technical solution of the present invention, the pharmaceutical composition for a single acupoint injection is a combination of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, and 200mg of vitamin B1.
本发明的优选技术方案中，单次穴位注射用的药物组合物含有鼠神经生长因子30-90ug、甲钴胺0.5-1.0mg、腺苷钴胺0.1-0.5mg，地塞米松2-5mg的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection contains 30-90ug of mouse nerve growth factor, 0.5-1.0mg of methylcobalamin, 0.1-0.5mg of adenosylcobalamin, and 2-5mg of dexamethasone. any one or combination thereof.
本发明的优选技术方案中，单次穴位注射用的药物组合物为鼠神经生长因子30-90ug、甲钴胺0.5-1.0mg、腺苷钴胺0.1-0.5mg，地塞米松2-5mg、100-300mg具有修复功效的神经修复细胞蛋白提取物和/或神经修复蛋白组合物的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for a single acupoint injection is mouse nerve growth factor 30-90ug, methylcobalamin 0.5-1.0mg, adenosylcobalamin 0.1-0.5mg, dexamethasone 2-5mg, 100-300 mg of any one or combination of nerve repair cell protein extracts and/or nerve repair protein compositions with repair effects.
本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg，地塞米松2mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical solution 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%.
本发明的优选技术方案中，单次穴位注射的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg，地塞米松5mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical solution of the present invention, the pharmaceutical composition for a 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%.
本发明的优选技术方案中，组合物中，单次穴位注射的药物组合物由鼠神经 生长因子90ug、甲钴胺1.0mg、腺苷钴胺0.5mg，地塞米松5mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical solution of the present invention, among the compositions, the pharmaceutical composition for single acupoint injection is derived from mouse nerve It consists of 90ug of growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride. The concentration of lidocaine hydrochloride is selected from 0.8%, 1%, 1.5% and 2%. any kind.
本发明的优选技术方案中，单次穴位注射的药物组合物由鼠神经生长因子60ug、甲钴胺0.8mg、腺苷钴胺0.5mg，地塞米松3mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical solution of the present invention, the pharmaceutical composition for a 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%.
本发明的优选技术方案中，所述单次穴位注射用的药物组合物任选地含有100-300mg具有修复功效的神经修复细胞蛋白提取物和/或神经修复蛋白组合物的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for a single acupoint injection optionally contains 100-300 mg of any one of the nerve repair cell protein extract and/or the nerve repair protein composition with repair effect, or any other thereof. combination.
本发明的优选技术方案中，所述单次穴位注射用的药物组合物临配临用。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is used on an ad hoc basis.
本发明的优选技术方案中，选取患侧面部的阳白穴、太阳穴、四白穴、迎香穴、巨髎穴、地仓穴和颊车穴进行穴位注射。In the preferred technical solution of the present invention, the Yangbai point, temple point, Sibai point, Yingxiang point, Juliiao point, Dicang point and Jieche point on the affected side of the face are selected for acupoint injection.
本发明的优选技术方案中，单次穴位注射用的药物组合物每天穴位注射一次，7天为疗程。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is injected once a day into the acupoint, and the treatment course is 7 days.
本发明的优选技术方案中，每次穴位注射治疗2-6个疗程，优选为4-5个疗程。In the preferred technical solution of the present invention, each acupoint injection treatment lasts for 2-6 courses, preferably 4-5 courses.
本发明的另一目的在于提供一种用于防治面瘫连带运动的药物组合物，选自鼠神经生长因子、单唾液酸神经节苷脂(GM1)、脑苷肌肽、甲钴胺、腺苷钴胺、复合维生素B、丁苯酞、马来酸桂哌齐特、依达拉奉、依达拉奉右莰醇、胞磷胆碱、胞磷胆碱钠、神经节苷脂、奥拉西坦、脑蛋白、吡拉西坦、神经生长因子、胞二磷胆碱、神经妥乐平、谷维素、维生素B1、维生素B6、维生素B12、维生素C、维生素E、复方脑肽节苷脂、茴拉西坦、神经酸、具有修复功效的神经修复细胞蛋白提取物或神经修复蛋白组合物的任一种或其组合。Another object of the present invention is to provide a pharmaceutical composition for preventing and treating facial paralysis associated movements, which is selected from the group consisting of mouse nerve growth factor, monosialoganglioside (GM1), cerebrospinalis carnosine, methylcobalamin, and adenosine cobalt. Amines, vitamin B complex, butylphthalide, cinpazide maleate, edaravone, edaravone dexbornillol, citicoline, citicoline sodium, gangliosides, olaxidine Tan, cerebroprotein, piracetam, nerve growth factor, citicoline, neurotropin, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin E, compound cerebroside, aniline Any one or a combination of racetam, nervonic acid, nerve repair cell protein extract with repair effect or nerve repair protein composition.
本发明的优选技术方案中，所述防治面瘫连带运动的药物组合物含有鼠神经生长因子、甲钴胺、腺苷钴的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating associated movements of facial paralysis contains any one of mouse nerve growth factor, methylcobalamin, adenosine cobalt, or a combination thereof.
本发明的优选技术方案中，所述用于防治面瘫连带运动的药物组合物由单次口服用的药物组合物和单次穴位注射用的药物组合物组成。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating associated movements of facial paralysis consists of a pharmaceutical composition for oral administration and a pharmaceutical composition for acupoint injection.
本发明的优选技术方案中，单次给药的药物组合物含有甲钴胺0.5-1.0mg、腺苷钴胺0.1-0.5mg的任一种或其组合。 In the preferred technical solution of the present invention, the pharmaceutical composition for single administration contains any one of 0.5-1.0 mg of methylcobalamin, 0.1-0.5 mg of adenosylcobalamin, or a combination thereof.
本发明的优选技术方案中，口服用药物组合物的给药方案为：口服甲钴胺0.5mg/次，3-4次/天，隔月服用；腺苷钴胺0.5mg/次，3次/天，连续3周，停1周，然后继续重复半年；In the preferred technical solution of the present invention, the dosage regimen of the oral pharmaceutical composition is: oral methylcobalamin 0.5 mg/time, 3-4 times/day, taken every other month; adenosylcobalamin 0.5 mg/time, 3 times/day days, 3 consecutive weeks, 1 week off, and then continue to repeat for half a year;
本发明的优选技术方案中，所述口服用药物组合物选自同时给药或序贯给药的任一种或其组合。In a preferred technical solution of the present invention, the oral pharmaceutical composition is selected from simultaneous administration or sequential administration or a combination thereof.
本发明的优选技术方案中，单次穴位注射用的药物组合物为鼠神经生长因子30ug、甲钴胺0.5mg、维生素B1 200mg的组合。In the preferred technical solution of the present invention, the pharmaceutical composition for a single acupoint injection is a combination of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, and 200mg of vitamin B1.
本发明的优选技术方案中，单次穴位注射用的药物组合物含有鼠神经生长因子30-90ug、甲钴胺0.5-1.0mg、腺苷钴胺0.1-0.5mg，地塞米松2-5mg的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection contains 30-90ug of mouse nerve growth factor, 0.5-1.0mg of methylcobalamin, 0.1-0.5mg of adenosylcobalamin, and 2-5mg of dexamethasone. any one or combination thereof.
本发明的优选技术方案中，单次穴位注射用的药物组合物为鼠神经生长因子30-90ug、甲钴胺0.5-1.0mg、腺苷钴胺0.1-0.5mg，地塞米松2-5mg、100-300mg具有修复功效的神经修复细胞蛋白提取物和/或神经修复蛋白组合物的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for a single acupoint injection is mouse nerve growth factor 30-90ug, methylcobalamin 0.5-1.0mg, adenosylcobalamin 0.1-0.5mg, dexamethasone 2-5mg, 100-300 mg of any one or combination of nerve repair cell protein extracts and/or nerve repair protein compositions with repair effects.
本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg，地塞米松2mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical solution 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%.
本发明的优选技术方案中，单次穴位注射的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg，地塞米松5mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical solution of the present invention, the pharmaceutical composition for a 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%.
本发明的优选技术方案中，组合物中，单次穴位注射的药物组合物由鼠神经生长因子90ug、甲钴胺1.0mg、腺苷钴胺0.5mg，地塞米松5mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical solution of the present invention, the pharmaceutical composition for a 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 Composition, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.
本发明的优选技术方案中，单次穴位注射的药物组合物由鼠神经生长因子60ug、甲钴胺0.8mg、腺苷钴胺0.5mg，地塞米松3mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical solution of the present invention, the pharmaceutical composition for a 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%.
本发明的优选技术方案中，所述单次穴位注射用的药物组合物任选地含有100-300mg具有修复功效的神经修复细胞蛋白提取物和/或神经修复蛋白组合物的任一种或其组合。 In the preferred technical solution of the present invention, the pharmaceutical composition for a single acupoint injection optionally contains 100-300 mg of any one of the nerve repair cell protein extract and/or the nerve repair protein composition with repair effect, or any other thereof. combination.
本发明的优选技术方案中，所述单次穴位注射用的药物组合物临配临用。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is used on an ad hoc basis.
本发明的优选技术方案中，选取患侧面部的阳白穴、太阳穴、四白穴、迎香穴、巨髎穴、地仓穴和颊车穴进行穴位注射。In the preferred technical solution of the present invention, the Yangbai point, temple point, Sibai point, Yingxiang point, Juliiao point, Dicang point and Jieche point on the affected side of the face are selected for acupoint injection.
本发明的优选技术方案中，单次穴位注射用的药物组合物每天穴位注射一次，7天为疗程。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is injected once a day into the acupoint, and the treatment course is 7 days.
本发明的优选技术方案中，每次穴位注射治疗2-6个疗程，优选为4-5个疗程。In the preferred technical solution of the present invention, each acupoint injection treatment lasts for 2-6 courses, preferably 4-5 courses.
本发明的优选技术方案中，所述用于防治面瘫连带运动的药物组合物任选地与射频手术、康复训练操的任一种或其组合联合使用。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating associated movements of facial paralysis is optionally used in combination with any one of radiofrequency surgery, rehabilitation training exercises, or a combination thereof.
本发明的优选技术方案中，所述射频手术在41℃-42℃、90V-140V、2Hz-6Hz条件下，基于长时程温控高电压变频脉冲射频800秒-1400秒。In the preferred technical solution of the present invention, the radiofrequency surgery is performed under the conditions of 41°C-42°C, 90V-140V, 2Hz-6Hz, based on long-term temperature-controlled high-voltage variable frequency pulse radiofrequency for 800 seconds to 1400 seconds.
本发明的优选技术方案中，所述射频手术在41℃-42℃、100V-120V、3Hz-5Hz条件下，基于长时程温控高电压变频脉冲射频960秒-1200秒。In the preferred technical solution of the present invention, the radiofrequency surgery is performed under the conditions of 41°C-42°C, 100V-120V, 3Hz-5Hz, based on long-term temperature-controlled high-voltage variable frequency pulse radiofrequency for 960 seconds to 1200 seconds.
本发明的优选技术方案中，所述康复训练操为发明人独创的面瘫康复训练操(著作权登记号：国作登字-2022-I-10250228和著作权登记号：国作登字-2022-F-10250229)。In the preferred technical solution of the present invention, the rehabilitation training exercises are facial paralysis rehabilitation training exercises originally created by the inventor (copyright registration number: Guozuodengzi-2022-I-10250228 and copyright registration number: Guozuodengzi-2022-F -10250229).
本发明的优选技术方案中，所述的康复操训练选自第一套康复操训练、第二套康复操训练的任一种或其组合。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, the second set of rehabilitation exercise training, or a combination thereof.
本发明的优选技术方案中，第一套康复操训练包括，一是照镜子；二是慢闭眼，闭眼5秒后，睁开眼保持5秒，同时控制不出现口角连带上提动作，纠偏纠正连带运动；每天训练第一套康复操三组，每组训练30遍。In the preferred technical solution of the present invention, the first set of rehabilitation exercise training includes: first, looking in the mirror; second, slowly closing the eyes. After closing the eyes for 5 seconds, open the eyes and hold for 5 seconds. At the same time, the mouth and corners are controlled not to be raised together. Correct deviations and correct joint movements; train three groups of the first set of rehabilitation exercises every day, each group training 30 times.
本发明的优选技术方案中，第二套康复操训练包括，一是照镜子；二是睁眼，尽量保持静默神经分支；三是口周噘嘴、呲牙和鼓腮；每天训练第一套康复操三组，每组训练10遍。In the preferred technical solution of the present invention, the second set of rehabilitation exercise training includes: first, looking in the mirror; second, opening the eyes and keeping silent nerve branches as much as possible; third, pouting, gnashing teeth and puffing cheeks around the mouth; training the first set every day Perform three groups of rehabilitation exercises, each group training 10 times.
本发明的优选技术方案中，所述防治恢复期面神经麻痹的治疗方案为，脉冲射频手术、术后口服给药和穴位注射给药以及术中和术后康复操训练。In the preferred technical solution of the present invention, the treatment plan for preventing and treating facial nerve paralysis in the recovery period includes pulsed radiofrequency surgery, postoperative oral administration and acupoint injection administration, and intraoperative and postoperative rehabilitation exercise training.
本发明的优选技术方案中，所述面神经麻痹选自面肌痉挛、面瘫/连带运动、三叉神经痛、舌咽神经痛、面神经炎、周围性面瘫、眼肌痉挛修复中的任一种或其组合。 In the preferred technical solution of the present invention, the facial nerve paralysis is selected from any one of hemifacial spasm, facial paralysis/joint movement, trigeminal neuralgia, glossopharyngeal neuralgia, facial neuritis, peripheral facial paralysis, ophthalmospastic repair, or their combinations. combination.
本发明的另一目的在于提供一种防治面瘫连带运动的治疗方案，所述治疗方案包括用于防治面瘫连带运动的药物组合物任选地与射频手术、康复训练操的任一种或其组合联合使用。Another object of the present invention is to provide a treatment plan for preventing and treating associated movements of facial paralysis. The treatment plan includes a pharmaceutical composition for preventing and treating associated movements of facial paralysis, optionally combined with any one of radiofrequency surgery, rehabilitation training exercises, or a combination thereof. Used in combination.
本发明的优选技术方案中，所述用于防治面瘫连带运动的药物组合物，选自鼠神经生长因子、单唾液酸神经节苷脂(GM1)、脑苷肌肽、甲钴胺、腺苷钴胺、复合维生素B、丁苯酞、马来酸桂哌齐特、依达拉奉、依达拉奉右莰醇、胞磷胆碱、胞磷胆碱钠、神经节苷脂、奥拉西坦、脑蛋白、吡拉西坦、神经生长因子、胞二磷胆碱、神经妥乐平、谷维素、维生素B1、维生素B6、维生素B12、维生素C、维生素E、复方脑肽节苷脂、茴拉西坦、神经酸、具有修复功效的神经修复细胞蛋白提取物或神经修复蛋白组合物的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating associated movements of facial paralysis is selected from the group consisting of mouse nerve growth factor, monosialoganglioside (GM1), cerebrospinalis carnosine, methylcobalamin, and adenosine cobalt. Amines, vitamin B complex, butylphthalide, cinpazide maleate, edaravone, edaravone dexbornillol, citicoline, citicoline sodium, gangliosides, olaxidine Tan, cerebroprotein, piracetam, nerve growth factor, citicoline, neurotropin, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin E, compound cerebroside, aniline Any one or a combination of racetam, nervonic acid, nerve repair cell protein extract with repair effect or nerve repair protein composition.
本发明的优选技术方案中，所述防治面瘫连带运动的药物组合物含有鼠神经生长因子、甲钴胺、腺苷钴的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating associated movements of facial paralysis contains any one of mouse nerve growth factor, methylcobalamin, adenosine cobalt, or a combination thereof.
本发明的优选技术方案中，所述用于防治面瘫连带运动的药物组合物由单次口服用的药物组合物和单次穴位注射用的药物组合物组成。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating associated movements of facial paralysis consists of a pharmaceutical composition for oral administration and a pharmaceutical composition for acupoint injection.
本发明的优选技术方案中，单次给药的药物组合物含有甲钴胺0.5-1.0mg、腺苷钴胺0.1-0.5mg的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for single administration contains any one of 0.5-1.0 mg of methylcobalamin, 0.1-0.5 mg of adenosylcobalamin, or a combination thereof.
本发明的优选技术方案中，口服用药物组合物的给药方案为：口服甲钴胺0.5mg/次，3-4次/天，隔月服用；腺苷钴胺0.5mg/次，3次/天，连续3周，停1周，然后继续重复半年；In the preferred technical solution of the present invention, the dosage regimen of the oral pharmaceutical composition is: oral methylcobalamin 0.5 mg/time, 3-4 times/day, taken every other month; adenosylcobalamin 0.5 mg/time, 3 times/day days, 3 consecutive weeks, 1 week off, and then continue to repeat for half a year;
本发明的优选技术方案中，所述口服用药物组合物选自同时给药或序贯给药的任一种或其组合。In a preferred technical solution of the present invention, the oral pharmaceutical composition is selected from simultaneous administration or sequential administration or a combination thereof.
本发明的优选技术方案中，单次穴位注射用的药物组合物为鼠神经生长因子30ug、甲钴胺0.5mg、维生素B1 200mg的组合。In the preferred technical solution of the present invention, the pharmaceutical composition for a single acupoint injection is a combination of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, and 200mg of vitamin B1.
本发明的优选技术方案中，单次穴位注射用的药物组合物含有鼠神经生长因子30-90ug、甲钴胺0.5-1.0mg、腺苷钴胺0.1-0.5mg，地塞米松2-5mg的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection contains 30-90ug of mouse nerve growth factor, 0.5-1.0mg of methylcobalamin, 0.1-0.5mg of adenosylcobalamin, and 2-5mg of dexamethasone. any one or combination thereof.
本发明的优选技术方案中，单次穴位注射用的药物组合物为鼠神经生长因子30-90ug、甲钴胺0.5-1.0mg、腺苷钴胺0.1-0.5mg，地塞米松2-5mg、100-300mg具 有修复功效的神经修复细胞蛋白提取物和/或神经修复蛋白组合物的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for a single acupoint injection is mouse nerve growth factor 30-90ug, methylcobalamin 0.5-1.0mg, adenosylcobalamin 0.1-0.5mg, dexamethasone 2-5mg, 100-300mg tool Any one or combination of nerve repair cell protein extracts and/or nerve repair protein compositions with repair effects.
本发明的优选技术方案中，单次穴位注射用的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg，地塞米松2mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical solution 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%.
本发明的优选技术方案中，单次穴位注射的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg，地塞米松5mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical solution of the present invention, the pharmaceutical composition for a 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%.
本发明的优选技术方案中，组合物中，单次穴位注射的药物组合物由鼠神经生长因子90ug、甲钴胺1.0mg、腺苷钴胺0.5mg，地塞米松5mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical solution of the present invention, the pharmaceutical composition for a 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 Composition, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.
本发明的优选技术方案中，单次穴位注射的药物组合物由鼠神经生长因子60ug、甲钴胺0.8mg、腺苷钴胺0.5mg，地塞米松3mg和盐酸利多卡因1ml组成，其中，盐酸利多卡因的浓度选自0.8％、1％、1.5％、2％的任一种。In the preferred technical solution of the present invention, the pharmaceutical composition for a 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%.
本发明的优选技术方案中，所述单次穴位注射用的药物组合物任选地含有100-300mg具有修复功效的神经修复细胞蛋白提取物和/或神经修复蛋白组合物的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for a single acupoint injection optionally contains 100-300 mg of any one of the nerve repair cell protein extract and/or the nerve repair protein composition with repair effect, or any other thereof. combination.
本发明的优选技术方案中，所述单次穴位注射用的药物组合物临配临用。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is used on an ad hoc basis.
本发明的优选技术方案中，选取患侧面部的阳白穴、太阳穴、四白穴、迎香穴、巨髎穴、地仓穴和颊车穴进行穴位注射。In the preferred technical solution of the present invention, the Yangbai point, temple point, Sibai point, Yingxiang point, Juliiao point, Dicang point and Jieche point on the affected side of the face are selected for acupoint injection.
本发明的优选技术方案中，单次穴位注射用的药物组合物每天穴位注射一次，7天为疗程。In the preferred technical solution of the present invention, the pharmaceutical composition for single acupoint injection is injected once a day into the acupoint, and the treatment course is 7 days.
本发明的优选技术方案中，每次穴位注射治疗2-6个疗程，优选为4-5个疗程。In the preferred technical solution of the present invention, each acupoint injection treatment lasts for 2-6 courses, preferably 4-5 courses.
本发明的优选技术方案中，所述用于防治面瘫连带运动的药物组合物任选地与射频手术、康复训练操的任一种或其组合联合使用。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating associated movements of facial paralysis is optionally used in combination with any one of radiofrequency surgery, rehabilitation training exercises, or a combination thereof.
本发明的优选技术方案中，所述射频手术在41℃-42℃、90V-140V、2Hz-6Hz条件下，基于长时程温控高电压变频脉冲射频800秒-1400秒。In the preferred technical solution of the present invention, the radiofrequency surgery is performed under the conditions of 41°C-42°C, 90V-140V, 2Hz-6Hz, based on long-term temperature-controlled high-voltage variable frequency pulse radiofrequency for 800 seconds to 1400 seconds.
本发明的优选技术方案中，所述射频手术在41℃-42℃、100V-120V、3Hz- 5Hz条件下，基于长时程温控高电压变频脉冲射频960秒-1200秒。In the preferred technical solution of the present invention, the radiofrequency surgery operates at 41°C-42°C, 100V-120V, 3Hz- Under the condition of 5Hz, based on long-term temperature control high voltage variable frequency pulse radio frequency 960 seconds-1200 seconds.
本发明的优选技术方案中，所述康复训练操为发明人独创的面瘫康复训练操(著作权登记号：国作登字-2022-I-10250228和著作权登记号：国作登字-2022-F-10250229)。In the preferred technical solution of the present invention, the rehabilitation training exercises are facial paralysis rehabilitation training exercises originally created by the inventor (copyright registration number: Guozuodengzi-2022-I-10250228 and copyright registration number: Guozuodengzi-2022-F -10250229).
本发明的优选技术方案中，所述的康复操训练选自第一套康复操训练、第二套康复操训练的任一种或其组合。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, the second set of rehabilitation exercise training, or a combination thereof.
本发明的优选技术方案中，第一套康复操训练包括，一是照镜子；二是慢闭眼，闭眼5秒后，睁开眼保持5秒，同时控制不出现口角连带上提动作，纠偏纠正连带运动；每天训练第一套康复操三组，每组训练30遍。In the preferred technical solution of the present invention, the first set of rehabilitation exercise training includes: first, looking in the mirror; second, slowly closing the eyes. After closing the eyes for 5 seconds, open the eyes and hold for 5 seconds. At the same time, the mouth and corners are controlled not to be raised together. Correct deviations and correct joint movements; train three groups of the first set of rehabilitation exercises every day, each group training 30 times.
本发明的优选技术方案中，第二套康复操训练包括，一是照镜子；二是睁眼，尽量保持静默神经分支；三是口周噘嘴、呲牙和鼓腮；每天训练第一套康复操三组，每组训练10遍。In the preferred technical solution of the present invention, the second set of rehabilitation exercise training includes: first, looking in the mirror; second, opening the eyes and keeping silent nerve branches as much as possible; third, pouting, gnashing teeth and puffing cheeks around the mouth; training the first set every day Perform three groups of rehabilitation exercises, each group training 10 times.
本发明的优选技术方案中，所述防治恢复期面神经麻痹的治疗方案为，脉冲射频手术、术后口服给药和穴位注射给药以及术中和术后康复操训练。In the preferred technical solution of the present invention, the treatment plan for preventing and treating facial nerve paralysis in the recovery period includes pulsed radiofrequency surgery, postoperative oral administration and acupoint injection administration, and intraoperative and postoperative rehabilitation exercise training.
本发明的优选技术方案中，所述面神经麻痹选自面肌痉挛、面瘫/连带运动、三叉神经痛、舌咽神经痛、面神经炎、周围性面瘫、眼肌痉挛修复中的任一种或其组合。In the preferred technical solution of the present invention, the facial nerve paralysis is selected from any one of hemifacial spasm, facial paralysis/joint movement, trigeminal neuralgia, glossopharyngeal neuralgia, facial neuritis, peripheral facial paralysis, ophthalmospastic repair, or their combinations. combination.
为了清楚地表述本发明，本发明所述的具有修复功效的神经修复细胞蛋白提取物或神经修复细胞蛋白组合物参照专利申请(CN2023100429139、PCT/CN2023/073566、CN2023100429143、PCT/CN2023/073582)制得。In order to clearly describe the present invention, the nerve repair cell protein extract or nerve repair cell protein composition with repair effect described in the present invention is prepared with reference to patent applications (CN2023100429139, PCT/CN2023/073566, CN2023100429143, PCT/CN2023/073582). have to.
本发明的优选技术方案中，所述具有神经修复功效的神经修复细胞蛋白提取物的制备方法，包括如下步骤：In the preferred technical solution of the present invention, the preparation method of the nerve repair cell protein extract with nerve repair effect includes the following steps:
S-1:将密度为5.0×106个/mL-5.0×107个/mL的间充质传代干细胞置于含有DMEM/F12 40-50％、RPMI1640 40-50％、牛血清蛋白(BSA)0.1-2％、表皮细胞生长因子(EGF)1-15ug/mL、成纤维细胞生长因子(FGF)1-15ug/mL、胰岛素转铁蛋白1-15ug/mL、复方氨基酸(18AA)0.01-0.1％和2-10μmol/L应激物的培养基中，再将其置于37.0℃±0.5℃、5％±1.0％CO2条件下培养2h-6h后，分离，洗涤，收集细胞，其中，所述的应激物选自化合物1-16的任一种或其组合；

S-1: Mesenchymal passaged stem cells with a density of 5.0×10 6 /mL-5.0×10 7 /mL were placed in DMEM/F12 40-50%, RPMI1640 40-50%, bovine serum albumin (BSA) )0.1-2%, epidermal growth factor (EGF) 1-15ug/mL, fibroblast growth factor (FGF) 1-15ug/mL, insulin transferrin 1-15ug/mL, compound amino acid (18AA) 0.01- 0.1% and 2-10 μmol/L stress medium, and then culture it at 37.0℃±0.5℃, 5%±1.0% CO2 for 2h-6h, separate, wash, and collect the cells, where , the stressor is selected from any one of compounds 1-16 or a combination thereof;

S-2：将收集细胞按照密度为5.0×106个/mL-5.0×107个/mL分散于溶剂中，再将其置于2℃-8℃条件下超声处理，制得细胞裂解液，其中，所述溶剂选自选自生理盐水、5％葡萄糖溶液、磷酸盐缓冲液(PBS)、TBPS缓冲液、TBST缓冲液、Tris缓冲液的任一种或其组合；S-2: Disperse the collected cells in the solvent at a density of 5.0×10 6 /mL-5.0×10 7 /mL, and then place them at 2℃-8℃ for ultrasonic treatment to prepare a cell lysis solution , wherein the solvent is selected from any one selected from physiological saline, 5% glucose solution, phosphate buffered saline (PBS), TBPS buffer, TBST buffer, Tris buffer or a combination thereof;
S-3:将步骤S-2制得的细胞裂解液分离后，所得的分离液依次经0.45um、0.22um滤膜过滤，即得。S-3: After separating the cell lysate prepared in step S-2, the obtained separation liquid is filtered through 0.45um and 0.22um filters in sequence.
本发明的优选技术方案中，步骤S-1的培养基中含有DMEM/F12 42-45％、RPMI1640 42-45％、牛血清蛋白(BSA)0.5-1.5％、表皮细胞生长因子(EGF)5-10ug/mL、成纤维细胞生长因子(FGF)5-10ug/mL、胰岛素转铁蛋白5-10ug/mL、复方氨基酸(18AA)0.02-0.05％和3-8μmol/L的应激物。In the preferred technical solution of the present invention, the culture medium of step S-1 contains DMEM/F12 42-45%, RPMI1640 42-45%, bovine serum albumin (BSA) 0.5-1.5%, epidermal cell 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 stressors.
本发明的优选技术方案中，步骤S-1的培养基中含有DMEM/F12 45％、RPMI1640 45％、牛血清蛋白(BSA)0.5％、表皮细胞生长因子(EGF)10ug/mL、成纤维细胞生长因子(FGF)10ug/mL，胰岛素转铁蛋白10ug/mL、复方氨基酸(18AA)0.05％和4-6μmol/L的应激物。In the preferred technical solution of the present invention, the culture medium of step S-1 contains DMEM/F12 45%, RPMI1640 45%, bovine serum albumin (BSA) 0.5%, epidermal growth factor (EGF) 10ug/mL, fibroblasts Growth factor (FGF) 10ug/mL, insulin transferrin 10ug/mL, compound amino acid (18AA) 0.05% and 4-6μmol/L stressors.
本发明的优选技术方案中，步骤S-1的间充质传代干细胞密度为8.0×106-2.0×107个/mL，优选为8.0×106-1.0×107个/mL。In the preferred technical solution of the present invention, the density of mesenchymal passage stem cells in step S-1 is 8.0×10 6 -2.0×10 7 cells/mL, preferably 8.0×10 6 -1.0×10 7 cells/mL.
本发明的优选技术方案中，步骤S-1的间充质传代干细胞在培养基中培养3h-5h，优选为3.5h-4.5h。In the preferred technical solution of the present invention, the mesenchymal passage stem cells in step S-1 are cultured in the culture medium for 3h-5h, preferably 3.5h-4.5h.
本发明的优选技术方案中，步骤S-1中洗涤细胞的溶剂选自生理盐水、5％葡萄糖溶液、磷酸盐缓冲液(PBS)、TBPS缓冲液、TBST缓冲液、Tris缓冲液的任一种或其组合,细胞洗涤次数为2-5次，优选为3-4次。In the 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 buffer (PBS), TBPS buffer, TBST buffer, and Tris buffer. Or a combination thereof, the number of cell washings is 2-5 times, preferably 3-4 times.
本发明的优选技术方案中，步骤S-1所述的分离选自离心、过滤的任一种或其组合，其中，所述离心条件为1000-2000rpm*3-15min，优选为1200rpm-1500rpm*5-10min。 In the preferred technical solution of the present invention, the separation described in step S-1 is selected from any one of centrifugation, filtration or a combination thereof, wherein the centrifugation conditions are 1000-2000rpm*3-15min, preferably 1200rpm-1500rpm* 5-10min.
本发明的优选技术方案中，步骤S-2的超声条件为：在2℃-8℃、25kHZ、360W条件下工作3s再间隙1s，超声处理1-5min。In the preferred technical solution of the present invention, the ultrasonic conditions of step S-2 are: working at 2°C-8°C, 25kHZ, 360W for 3 seconds, followed by a gap of 1 second, and ultrasonic treatment for 1-5 minutes.
本发明的优选技术方案中，步骤S-3所述分离选自2000-8000rpm*10-30min离心、多级离心、多级过滤的任一种或其组合，优选为3000-7000rpm*15-25min。In the preferred technical solution of the present invention, the separation described 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 .
本发明的优选技术方案中，步骤S-3的多级离心依次为3000-4000rpm*3-5min、5000-6000rpm*3-5min和7000rpm*5-8min。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.
本发明的优选技术方案中，所述多级过滤的滤膜孔径选自80um、50um、30um、10um、5um的任一种。In the preferred technical solution of the present invention, the filter membrane pore size of the multi-stage filtration is selected from any one of 80um, 50um, 30um, 10um, and 5um.
本发明的优选技术方案中，将步骤S-3制得的细胞蛋白提取物冻存，优选冻存于-40℃至-20℃。In the preferred technical solution of the present invention, the cell protein extract prepared in step S-3 is frozen and stored, preferably at -40°C to -20°C.
本发明的优选技术方案中，将步骤S-3制得的细胞蛋白提取物采用核酸酶或全能核酸酶的任一种酶解后再分离纯化。In the preferred technical solution of the present invention, the cell protein extract prepared in step S-3 is enzymatically hydrolyzed by either a nuclease or a totipotent nuclease and then separated and purified.
本发明的优选技术方案中，所述间充质传代干细胞的培养或原代间充质干细胞的培养采用本领域的培养方法。In the preferred technical solution of the present invention, the culture of mesenchymal passaged stem cells or the culture of primary mesenchymal stem cells adopts the culture methods in this field.
本发明的优选技术方案中，所述间充质传代干细胞的培养包括下述步骤：将原代间充质干细胞按照初始密度为5.0×105-5.0×106个/ml加入到传代培养基中，再将其置于37.0℃±0.5℃、5％±1.0％CO2条件下培养10-15天，每隔2-3天，观察传代培养基变黄后，半量更换传代培养基，其中，所述传代培养基含有10％FBS、100U/ml青霉素和100ug/ml链霉素的DMEM/F12培养基。In the preferred technical solution of the present invention, the culture of mesenchymal passage stem cells includes the following steps: adding primary mesenchymal stem cells to the passage medium at an initial density of 5.0×10 5 -5.0×10 6 /ml. , and then place it in the culture medium at 37.0℃±0.5℃ and 5%±1.0% CO2 for 10-15 days. Every 2-3 days, after observing that the subculture medium turns yellow, replace half of the subculture medium. , the subculture medium contains DMEM/F12 medium with 10% FBS, 100 U/ml penicillin and 100ug/ml streptomycin.
本发明的优选技术方案中，所述原代间充质干细胞的培养包括下述步骤：In the preferred technical solution of the present invention, the culture of primary mesenchymal stem cells includes the following steps:
1)将脐带清洗消毒后，组织解剖，取华通胶层组织，将其切成3mm3的小块，离心，清洗，收集组织块，将其置于含10％胎牛血清FBS、100ug/ml青霉素、100ug/ml链霉素的DMEM/F12培养基中，再将其置于37.0℃±0.5℃、5％±1.0％CO2条件下培养，每间隔2-3天半量更换培养基，培养至组织块爬出细胞；1) After cleaning and disinfecting the umbilical cord, dissect the tissue, take the Huatong glue layer tissue, cut it into small pieces of 3mm3 , centrifuge, clean, collect the tissue pieces, and place them in a solution containing 10% fetal bovine serum FBS, 100ug/ ml penicillin and 100ug/ml streptomycin in DMEM/F12 culture medium, and then culture it under the conditions of 37.0℃±0.5℃, 5%±1.0% CO2 , and replace the medium with half the medium every 2-3 days. Culture until cells crawl out of the tissue block;
2)振摇，收集低层细胞用PBS清洗后，加入0.25％的胰蛋白酶消化2min-3min，加入等体积的胰蛋白酶终止液停止消化，吸管轻轻吹打，1200-1500rpm/min*5-8min离心后，收集细胞，即得。 2) Shake, collect the lower layer cells and wash with PBS, add 0.25% trypsin for digestion for 2min-3min, add an equal volume of trypsin stop solution to stop digestion, gently pipette, and centrifuge at 1200-1500rpm/min*5-8min Afterwards, collect the cells and you are ready.
除非另有说明，本发明涉及液体与液体之间的百分比时，所述的百分比为体积/体积百分比；本发明涉及液体与固体之间的百分比时，所述百分比为体积/重量百分比；本发明涉及固体与液体之间的百分比时，所述百分比为重量/体积百分比；其余为重量/重量百分比。Unless otherwise stated, when the present invention relates to the percentage between liquid and liquid, the percentage is volume/volume percentage; when the present invention relates to the percentage between liquid and solid, the percentage is volume/weight percentage; the present invention When referring to percentages between solids and liquids, the percentages are weight/volume; the remainder are weight/weight.
除非另有说明，本发明采用如下方法进行评价：Unless otherwise stated, the present invention adopts the following methods for evaluation:
1.取穴：按照由国家技术监督局发布的中华人民共和国国家标准《腧穴名称与定位》(GB/T 12345-2006)的穴位以定位。1. Acupoint selection: Position the acupoints in accordance with the National Standard of the People's Republic of China "Acupoint Names and Positioning" (GB/T 12345-2006) issued by the State Bureau of Technical Supervision.
2.面瘫运动功能评价量表2. Facial paralysis motor function evaluation scale
3.面瘫生活质量评价量表3. Facial paralysis quality of life evaluation scale
与现有技术相比，本发明具有下述有益效果：Compared with the prior art, the present invention has the following beneficial effects:
1、本发明采用射频方法用于面瘫连带运动的治疗，不需要开放手术，避免了传统治疗的创伤和疼痛，配合治疗连带运动的药物组合物，各组分协同增效，药物组合物起效快、持续作用时间延长、治疗效果好，能降低单一药物使用时带来的副作用，同时加速改善面瘫症状，治疗安全可靠，无明显的副作用和并发症。1. The present invention adopts radio frequency method for the treatment of joint movement of facial paralysis, which does not require open surgery and avoids the trauma and pain of traditional treatment. With the pharmaceutical composition for treating joint movement, each component synergizes and the pharmaceutical composition takes effect. It has fast, prolonged action and good therapeutic effect. It can reduce the side effects caused by the use of a single drug and accelerate the improvement of facial paralysis symptoms. The treatment is safe and reliable, without obvious side effects and complications.
2、本发明可节约药物使用量，显著降低生产成本，操作简便、适合于大规模工业化生产等优点。2. The present invention can save the amount of medicine used, significantly reduce production costs, is easy to operate, and is suitable for large-scale industrial production.
具体实施方式Detailed ways
下面结合具体实施例对本发明的详细内容做进一步解释和描述，但并不以此限制本发明的保护范围。The details of the present invention will be further explained and described below in conjunction with specific embodiments, but this does not limit the scope of the present invention.
实施例1具有修复功效的神经修复细胞蛋白提取物的制备 Example 1 Preparation of nerve repair cell protein extract with repair effect
1、原代间充质干细胞的培养1. Culture of primary mesenchymal stem cells
原代间充质干细胞的培养包括下述步骤：The culture of primary mesenchymal stem cells includes the following steps:
1)将脐带清洗消毒后，组织解剖，取华通胶层组织，将其切成3mm3的小块，离心，清洗，收集组织块，将其置于培养瓶中，加入含10％胎牛血清FBS、100ug/ml青霉素、100ug/ml链霉素的DMEM/F12培养基，再将其置于37℃、5％CO2条件下培养，促进其贴壁，每间隔2-3天,观察培养基变黄后，半量更换培养基，培养10-12天，至组织块边上可见细胞爬出；1) After cleaning and disinfecting the umbilical cord, dissect the tissue, take the Huatong glue layer tissue, cut it into 3mm3 small pieces, centrifuge, clean, collect the tissue pieces, place them in a culture bottle, add 10% fetal bovine DMEM/F12 culture medium with serum FBS, 100ug/ml penicillin, and 100ug/ml streptomycin, and then culture it at 37°C and 5% CO2 to promote adhesion. Observe every 2-3 days. After the medium turns yellow, replace half of the medium and culture for 10-12 days until cells can be seen crawling out from the edge of the tissue block;
2)轻轻摇晃，使组织块掉落，分别收集组织块和低层细胞，其中，将收集 的组织块再贴壁培养；2) Shake gently to make the tissue blocks fall, and collect the tissue blocks and low-layer cells respectively. Among them, the collected The tissue block is re-attached and cultured;
3)将收集的低层细胞用PBS清洗后，加入适量0.25％胰蛋白酶消化2min-3min，加入等体积的胰蛋白酶终止液停止消化，吸管轻轻吹打瓶底，1500rpm*5min离心后，收集细胞，即得。3) Wash the collected lower-layer cells with PBS, add an appropriate amount of 0.25% trypsin for digestion for 2 to 3 minutes, add an equal volume of trypsin stop solution to stop digestion, gently tap the bottom of the bottle with a pipette, and centrifuge at 1500 rpm for 5 minutes to collect the cells. That’s it.
2、原代间充质干细胞的传代培养(间充质传代干细胞的培养)2. Passage culture of primary mesenchymal stem cells (culture of mesenchymal stem cells)
原代间充质干细胞的传代培养(间充质传代干细胞的培养)：将原代间充质干细胞按照初始密度为5.0×105-5.0×106个/ml加入到含有10％FBS、100U/ml青霉素和100ug/ml链霉素的DMEM/F12培养基中，再将其置于37.0℃±0.5℃、5％±1.0％CO2条件下培养10-15天，每间隔2-3天，观察培养基变黄后，半量更换培养基。Passage culture of primary mesenchymal stem cells (culture of mesenchymal stem cells): Add primary mesenchymal stem cells at an initial density of 5.0×10 5 -5.0×10 6 /ml into a solution containing 10% FBS and 100U /ml penicillin and 100ug/ml streptomycin in DMEM/F12 culture medium, and then culture it at 37.0℃±0.5℃, 5%±1.0% CO2 for 10-15 days, with an interval of 2-3 days , after observing that the medium turns yellow, replace the medium by half.
3、化合物1-16的制备参照文献1(New limonophyllines A-C from the stem of Atalantia monophylla and cytotoxicity against cholangiocarcinoma and HepG2 cell lines，Arch.Pharm.Res.(2018)41:431–437)。3. For the preparation of compounds 1-16, refer to literature 1 (New limonophyllines A-C from the stem of Atalantia monophylla and cytotoxicity against cholangiocarcinoma and HepG2 cell lines, Arch.Pharm.Res. (2018) 41:431–437).
具有神经修复功效的神经修复细胞蛋白提取物的制备方法，包括如下步骤：The preparation method of nerve repair cell protein extract with nerve repair effect includes the following steps:
(1)将间充质传代细胞按照密度为8.0×106个/mL加入到含有DMEM/F12 45％、RPMI1640 45％、牛血清蛋白(BSA)0.5％、表皮细胞生长因子(EGF)10ug/mL、成纤维细胞生长因子(FGF)10ug/mL、胰岛素转铁蛋白10ug/mL、复方氨基酸(18AA)0.05％和5μmol/L的化合物16的培养基中，再将其置于37℃、5％CO2条件下培养4h后，将其置于1200rpm*5min离心，用PBS洗涤3次后，收集细胞；(1) Add mesenchymal passage cells at a density of 8.0×10 6 cells/mL into a solution containing DMEM/F12 45%, RPMI1640 45%, bovine serum albumin (BSA) 0.5%, and epidermal growth factor (EGF) 10ug/ mL, fibroblast growth factor (FGF) 10ug/mL, insulin transferrin 10ug/mL, compound amino acid (18AA) 0.05% and 5 μmol/L compound 16, and then placed at 37°C, 5 After culturing for 4 hours under % CO2 conditions, centrifuge at 1200rpm*5min, wash 3 times with PBS, and collect the cells;
(2)将步骤(1)收集的细胞按照密度为1.0×107个/mL分散于生理盐水中，在2-8℃、25kHz、360W条件下超声3s、间隙1s，超声2min，制得细胞裂解液；(2) Disperse the cells collected in step (1) in physiological saline at a density of 1.0 × 10 7 cells/mL, ultrasonicate for 3s, 1s gap, and 2min under the conditions of 2-8°C, 25kHz, 360W to obtain cells. Lysis solution;
(3)将步骤(2)制得的细胞裂解液置于7000rpm*20min离心，将所得的离心液依次经0.45um、0.22um滤膜过滤，即得细胞蛋白提取物；(3) Centrifuge the cell lysate prepared in step (2) at 7000rpm*20min, and filter the obtained centrifuge through 0.45um and 0.22um filters in sequence to obtain the cell protein extract;
(4)在步骤(3)制得的细胞蛋白提取物加入所需量的甘露醇，搅拌，混合均匀后，冻干，所得冻干制剂中含有5％的甘露醇(m/m)。(4) Add the required amount of mannitol to the cell protein extract prepared in step (3), stir, mix evenly, and freeze-dry. The resulting freeze-dried preparation contains 5% mannitol (m/m).
试验例1本发明药物组合物用于面瘫连带运动的治疗效果研究 Test Example 1 Study on the therapeutic effect of the pharmaceutical composition of the present invention on facial paralysis and associated movements
选取面瘫连带运动患者40名，分为1组(10名)、2组(20名)、3组(10 名)。患者入组标准：符合连带运动中医、西医诊断标准，患者发病超过6个月；年龄20-70岁；H-B分级在II级以上；知情同意接受本试验；依从性好。禁忌症：面神经完全断裂或缺失者；穿刺部位感染或皮肤损伤者；累及面神经的局部肿瘤或其他占位性病变者；凝血功能障碍者，可能增加出血或血肿的风险；心脏起搏器植入者，可能干扰起搏器的正常工作；孕妇或哺乳期妇女者，可能影响胎儿或婴儿的健康；对电极针或局部麻醉药过敏者，可能引起过敏反应或其他不良反应；精神障碍或无法配合康复或矫正训练治疗者。Forty patients with facial paralysis and associated motion were selected and divided into Group 1 (10 patients), Group 2 (20 patients), and Group 3 (10 patients). name). Patient inclusion criteria: meet the diagnostic criteria of joint sports traditional Chinese medicine and Western medicine, the patient has been ill for more than 6 months; age is 20-70 years old; HB grade is above level II; informed consent to accept this trial; good compliance. Contraindications: Patients with complete rupture or loss of the facial nerve; infection or skin damage at the puncture site; patients with local tumors or other space-occupying lesions involving the facial nerve; patients with coagulation dysfunction, which may increase the risk of bleeding or hematoma; pacemaker implantation Those who are allergic may interfere with the normal work of the pacemaker; those who are pregnant or lactating may affect the health of the fetus or baby; those who are allergic to electrode needles or local anesthetics may cause allergic reactions or other adverse reactions; those who are mentally disordered or unable to cooperate Rehabilitation or corrective training therapist.
1组的治疗方案(每个疗程7天，治疗4个疗程)：单次穴位注射的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、维生素B1 200mg组成，临配临用，选取患侧面部的阳白穴、太阳穴、四白穴、迎香穴、巨髎穴、地仓穴和颊车穴进行穴位注射，每天穴位注射1次。Treatment plan for Group 1 (7 days for each course, 4 courses of treatment): The pharmaceutical composition for a single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, and 200mg of vitamin B1. Acupoint injections are performed at the Yangbai point, temple point, Sibai point, Yingxiang point, Juliiao point, Dicang point and Jieche point on the affected side of the face, once a day.
2组的治疗方案(每个疗程7天，治疗4个疗程)包括脉冲射频手术、术后口服给药和穴位注射给药以及术中和术后康复操训练。The treatment plan for the 2 groups (each course is 7 days, 4 courses of treatment) includes pulsed radiofrequency surgery, postoperative oral administration and acupoint injection administration, as well as intraoperative and postoperative rehabilitation exercise training.
1、脉冲射频手术：采用射频控温热凝器(型号R-2000B M1，购自北琪医疗)，基于长时程温控高电压变频脉冲射频技术对病变部位进行神经激活修复调控微纠偏手术(脉冲宽度20ms、静息期480ms、最大电压值100V、脉冲频率2HZ)，在41-42℃、90-140V、2-5Hz条件下脉冲射频1200秒；手术中，配合2组睁大眼保持、重复龇牙和重复鼓气的面部运动；1. Pulsed radiofrequency surgery: Using a radiofrequency temperature-controlled coagulator (model R-2000B M1, purchased from Beiqi Medical), based on long-term temperature-controlled high-voltage variable frequency pulsed radiofrequency technology, nerve activation, repair, regulation and micro-correction surgery are performed on the lesion. (Pulse width 20ms, resting period 480ms, maximum voltage value 100V, pulse frequency 2HZ), pulse radio frequency for 1200 seconds under the conditions of 41-42℃, 90-140V, 2-5Hz; during the operation, two groups of eyes were kept open , facial movements that repeatedly show teeth and puff;
2、术后口服药物的同时给药和/或序贯给药的方案：2. Simultaneous and/or sequential administration of oral medications after surgery:
术后口服甲钴胺0.5mg/次，4次/天，隔月服用；腺苷钴胺0.5mg/次，3次/天，连续3周，停1周，然后继续服用半年；After surgery, take oral 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 taking it for half a year;
3、术后穴位注射给药方案：3. Postoperative acupoint injection medication regimen:
单次穴位注射的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg、地塞米松5mg和盐酸利多卡因1ml组成，临配临用，选取患侧面部的阳白穴、太阳穴、四白穴、迎香穴、巨髎穴、地仓穴和颊车穴进行穴位注射，每天穴位注射1次。The pharmaceutical composition for a 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. Acupoint injection is performed at Yangbai point, Taiyang point, Sibai point, Yingxiang point, Juliiao point, Dicang point and Jieche point, once a day.
4、术后康复操训练：4. Postoperative rehabilitation exercise training:
第一套康复操：一是照镜子；二是慢闭眼，闭眼5秒后，睁开眼保持5秒，同时控制不出现口角连带上提动作，纠偏纠正连带运动。每天训练三组，每组训 练30遍；第二套康复操：一是照镜子；二是睁眼，尽量保持静默神经分支；三是口周噘嘴、呲牙和鼓腮。每天训练三组，每组训练10遍。The first set of rehabilitation exercises: first, look in the mirror; second, slowly close your eyes. After closing your eyes for 5 seconds, open your eyes and hold them for 5 seconds. At the same time, you should control the mouth and corners to avoid joint lifting movements, and correct deviations and joint movements. Train three groups every day, each group trains Practice 30 times; the second set of rehabilitation exercises: first, look in the mirror; second, open your eyes and try to keep the nerve branches as silent as possible; third, pout, clenched teeth and puffed cheeks around the mouth. Train three groups a day, each group training 10 times.
3组的治疗方案(每个疗程7天，治疗4个疗程)包括脉冲射频手术、术后口服给药和穴位注射给药以及术中和术后康复操训练。The treatment plan of the 3 groups (each course is 7 days, 4 courses of treatment) includes pulsed radiofrequency surgery, postoperative oral administration and acupoint injection administration, as well as intraoperative and postoperative rehabilitation exercise training.
1、脉冲射频手术：采用射频控温热凝器(型号R-2000B M1，购自北琪医疗)，基于长时程温控高电压变频脉冲射频技术对病变部位进行神经激活修复调控微纠偏手术(脉冲宽度20ms、静息期480ms、最大电压值100V、脉冲频率2HZ)，在41-42℃、90-140V、2-5Hz条件下脉冲射频1200秒；手术中，配合2组睁大眼保持、重复龇牙和重复鼓气的面部运动；1. Pulsed radiofrequency surgery: Using a radiofrequency temperature-controlled coagulator (model R-2000B M1, purchased from Beiqi Medical), based on long-term temperature-controlled high-voltage variable frequency pulsed radiofrequency technology, nerve activation, repair, regulation and micro-correction surgery are performed on the lesion. (Pulse width 20ms, resting period 480ms, maximum voltage value 100V, pulse frequency 2HZ), pulse radio frequency for 1200 seconds under the conditions of 41-42℃, 90-140V, 2-5Hz; during the operation, two groups of eyes were kept open , facial movements that repeatedly show teeth and puff;
2、术后口服药物的同时给药和/或序贯给药的方案：2. Simultaneous and/or sequential administration of oral medications after surgery:
术后口服甲钴胺0.5mg/次，4次/天，隔月服用；腺苷钴胺0.5mg/次，3次/天，连续3周，停1周，然后继续服用半年；After surgery, take oral 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 taking it for half a year;
3、术后穴位注射给药方案：3. Postoperative acupoint injection medication regimen:
(1)单次穴位注射的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg、地塞米松5mg和盐酸利多卡因1ml组成，临配临用，选取患侧面部的阳白穴、太阳穴、四白穴、迎香穴、巨髎穴、地仓穴和颊车穴进行穴位注射，每天穴位注射1次。(1) The pharmaceutical composition for a 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. Acupoint injections are performed at the Yangbai point, temple point, Sibai point, Yingxiang point, Juliiao point, Dicang point and Jieche point on the side face, once a day.
(2)单次穴位注射实施例1制得的神经修复细胞蛋白提取物冻干制剂130ug，用2ml生理盐水溶解，选取患侧面部的阳白穴、太阳穴、四白穴、迎香穴、巨髎穴、地仓穴和颊车穴、对侧太阳穴、地仓穴，双手合谷穴进行穴位注射，每天穴位注射1次。(2) A single acupoint injection of 130ug of the freeze-dried preparation of nerve repair cell protein extract prepared in Example 1 was dissolved in 2 ml of physiological saline. Select the Yangbai point, temple, Sibai point, Yingxiang point, and Ju on the affected side of the face Acupoint injections were performed at Liao, Dicang and Jieche points, the temple on the opposite side, Dicang point, and Hegu point on both hands, once a day.
4、术后康复操训练：4. Postoperative rehabilitation exercise training:
第一套康复操：一是照镜子；二是慢闭眼，闭眼5秒后，睁开眼保持5秒，同时控制不出现口角连带上提动作，纠偏纠正连带运动。每天训练三组，每组训练30遍；第二套康复操：一是照镜子；二是睁眼，尽量保持静默神经分支；三是口周噘嘴、呲牙和鼓腮。每天训练三组，每组训练10遍。The first set of rehabilitation exercises: first, look in the mirror; second, slowly close your eyes. After closing your eyes for 5 seconds, open your eyes and hold them for 5 seconds. At the same time, you should control the mouth and corners to avoid joint lifting movements, and correct deviations and joint movements. Three groups are trained every day, each group is trained 30 times; the second set of rehabilitation exercises: the first is to look in the mirror; the second is to open the eyes and try to keep the silent nerve branches; the third is to pout, gnash the teeth and puff out the cheeks around the mouth. Train three groups a day, each group training 10 times.
疗效评定：满意度调查表和临床评分House-Brakmann面神经功能分级疗效评价表。

Efficacy evaluation: Satisfaction questionnaire and clinical rating House-Brakmann facial nerve function classification efficacy evaluation form.

1组：重复治疗4-6个疗程，超过50％的患者症状改善。Group 1: Repeated treatment for 4-6 courses, more than 50% of patients' symptoms improved.
2组：即刻有效率为70％，显效率50％。患者术后满意度80％。全部受试患者均无副作用和不良事件。6个月内重复治疗2～3次，疗效累积。Group 2: Immediate effective rate is 70%, apparent efficiency is 50%. Postoperative patient satisfaction was 80%. All tested patients had no side effects or adverse events. Repeat the treatment 2 to 3 times within 6 months, and the therapeutic effects will accumulate.
3组：患者连带运动症状显著改善，即刻有效率为100％，显效率90％。患者术后满意度100％。全部受试患者均无副作用和不良事件，无复发。Group 3: The patients' associated motor symptoms were significantly improved, with an immediate effective rate of 100% and a significant efficiency of 90%. Postoperative patient satisfaction was 100%. All tested patients had no side effects, adverse events, or recurrence.
以上对本发明具体实施方式的描述并不限制本发明，本领域技术人员可以根据本发明作出各种改变或变形，只要不脱离本发明的精神，均应属于本发明权利要求保护的范围。 The above description of the specific embodiments of the present invention does not limit the present invention. Those skilled in the art can make various changes or deformations according to the present invention. As long as they do not deviate from the spirit of the present invention, they should all fall within the scope of protection of the claims of the present invention.

Claims (10)

  1. 射频装置在治疗面瘫连带运动中的应用，所述射频手术在41℃-42℃、90V-140V、2Hz-6Hz条件下，基于长时程温控高电压变频脉冲射频800秒-1400秒。The application of radiofrequency devices in the treatment of facial paralysis and associated movements. The radiofrequency surgery is performed under the conditions of 41℃-42℃, 90V-140V, 2Hz-6Hz, and is based on long-term temperature-controlled high-voltage variable frequency pulse radiofrequency for 800 seconds to 1400 seconds.
  2. 如权利要求1所述的应用，所述射频手术在41℃-42℃、100V-120V、3Hz-5Hz条件下，基于长时程温控高电压变频脉冲射频960秒-1200秒。As claimed in claim 1, the radiofrequency surgery is performed under the conditions of 41°C-42°C, 100V-120V, 3Hz-5Hz, based on long-term temperature-controlled high-voltage variable frequency pulse radiofrequency for 960 seconds to 1200 seconds.
  3. 如权利要求1-2任一项所述的应用，所述射频手术任选地与用于防治面瘫连带运动的药物组合物、康复训练操的任一种或其组合联合使用。The application according to any one of claims 1-2, the radiofrequency surgery is optionally used in combination with any one of a pharmaceutical composition for preventing and treating associated movements of facial paralysis, rehabilitation training exercises, or a combination thereof.
  4. 如权利要求1-4任一项所述的应用，所述面瘫选自面肌痉挛、面瘫/连带运动、三叉神经痛、舌咽神经痛、面神经炎、周围性面瘫、眼肌痉挛修复中的任一种或其组合。The application according to any one of claims 1 to 4, wherein the facial paralysis is selected from the group consisting of hemifacial spasm, facial paralysis/joint movement, trigeminal neuralgia, glossopharyngeal neuralgia, facial neuritis, peripheral facial paralysis, and ophthalmospastic repair. any one or combination thereof.
  5. 如权利要求1-4任一项所述的应用，所述用于防治面瘫连带运动的药物组合物，选自鼠神经生长因子、单唾液酸神经节苷脂(GM1)、脑苷肌肽、甲钴胺、腺苷钴胺、复合维生素B、丁苯酞、马来酸桂哌齐特、依达拉奉、依达拉奉右莰醇、胞磷胆碱、胞磷胆碱钠、神经节苷脂、奥拉西坦、脑蛋白、吡拉西坦、神经生长因子、胞二磷胆碱、神经妥乐平、谷维素、维生素B1、维生素B6、维生素B12、维生素C、维生素E、复方脑肽节苷脂、茴拉西坦、神经酸、具有修复功效的神经修复细胞蛋白提取物或神经修复蛋白组合物的任一种或其组合。The application according to any one of claims 1 to 4, wherein the pharmaceutical composition for preventing and treating facial paralysis and associated movements is selected from the group consisting of mouse nerve growth factor, monosialoganglioside (GM1), cerebrospinalis carnosine, alpha- Cobalamin, adenosylcobalamin, vitamin B complex, butylphthalide, cinepazide maleate, edaravone, edaravone dextroborneol, citicoline, citicoline sodium, ganglion Glycosides, oxiracetam, cerebroprotein, piracetam, nerve growth factor, citicoline, neurotropin, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin E, compound brain peptide Any one or a combination of anthroside, aniracetam, nervonic acid, nerve repair cell protein extract with repair effect or nerve repair protein composition.
  6. 如权利要求1-5任一项所述的应用，所述防治面瘫连带运动的药物组合物含有鼠神经生长因子、甲钴胺、腺苷钴的任一种或其组合。The application according to any one of claims 1 to 5, wherein the pharmaceutical composition for preventing and treating facial paralysis associated movements contains any one of mouse nerve growth factor, methylcobalamin, adenosine cobalt or a combination thereof.
  7. 如权利要求1-6任一项所述的应用，单次穴位注射用的药物组合物含有鼠神经生长因子30-90ug、甲钴胺0.5-1.0mg、腺苷钴胺0.1-0.5mg，地塞米松2-5mg的任一种或其组合。The application according to any one of claims 1 to 6, the pharmaceutical composition for single acupoint injection contains 30-90ug of mouse nerve growth factor, 0.5-1.0 mg of methylcobalamin, 0.1-0.5 mg of adenosylcobalamin, and Dexamethasone 2-5 mg of any one or combination thereof.
  8. 如权利要求1-7任一项所述的应用，所述单次穴位注射用的药物组合物任选地含有100-300mg具有修复功效的神经修复细胞蛋白提取物和/或神经修复蛋白组合物的任一种或其组合。The application according to any one of claims 1 to 7, the pharmaceutical composition for single acupoint injection optionally contains 100-300 mg of nerve repair cell protein extract and/or nerve repair protein composition with repair effect any one or combination thereof.
  9. 一种用于防治面瘫连带运动的药物组合物，选自鼠神经生长因子、单唾液酸神经节苷脂(GM1)、脑苷肌肽、甲钴胺、腺苷钴胺、复合维生素B、丁苯酞、马来酸桂哌齐特、依达拉奉、依达拉奉右莰醇、胞磷胆碱、胞磷胆碱钠、神经节苷脂、奥拉西坦、脑蛋白、吡拉西坦、神经生长因子、胞二磷胆碱、神经妥乐平、 谷维素、维生素B1、维生素B6、维生素B12、维生素C、维生素E、复方脑肽节苷脂、茴拉西坦、神经酸、具有修复功效的神经修复细胞蛋白提取物或神经修复蛋白组合物的任一种或其组合。A pharmaceutical composition for preventing and treating associated movements of facial paralysis, selected from the group consisting of mouse nerve growth factor, monosialoganglioside (GM1), cerebrospinalis carnosine, methylcobalamin, adenosylcobalamin, vitamin B complex, and butylbenzene Phthalate, cinepazide maleate, edaravone, edaravone dexbornillol, citicoline, citicoline sodium, gangliosides, oxiracetam, cephalin, piracetam Tan, nerve growth factor, citicoline, neurotropin, Any of oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin E, compound cerebroside glycosides, aniracetam, nervonic acid, nerve repair cell protein extract with repair effect or nerve repair protein composition one or a combination thereof.
  10. 一种防治面瘫连带运动的治疗方案，所述治疗方案包括用于如权利要求9所述的防治面瘫连带运动的药物组合物任选地与射频手术、康复训练操的任一种或其组合联合使用。 A treatment plan for preventing and treating associated movements of facial paralysis, which treatment plan includes a pharmaceutical composition for preventing and treating associated movements of facial paralysis as claimed in claim 9, optionally combined with any one of radiofrequency surgery, rehabilitation training exercises, or a combination thereof use.
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