WO2024051845A1 - Pharmaceutical composition for preventing and treating sequelae stage facial nerve paralysis, and use thereof - Google Patents
Pharmaceutical composition for preventing and treating sequelae stage facial nerve paralysis, and use thereof Download PDFInfo
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- WO2024051845A1 WO2024051845A1 PCT/CN2023/117897 CN2023117897W WO2024051845A1 WO 2024051845 A1 WO2024051845 A1 WO 2024051845A1 CN 2023117897 W CN2023117897 W CN 2023117897W WO 2024051845 A1 WO2024051845 A1 WO 2024051845A1
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- pharmaceutical composition
- vitamin
- present
- preventing
- sequelae
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- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/40—Applying electric fields by inductive or capacitive coupling ; Applying radio-frequency signals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A63—SPORTS; GAMES; AMUSEMENTS
- A63B—APPARATUS FOR PHYSICAL TRAINING, GYMNASTICS, SWIMMING, CLIMBING, OR FENCING; BALL GAMES; TRAINING EQUIPMENT
- A63B23/00—Exercising apparatus specially adapted for particular parts of the body
- A63B23/025—Exercising apparatus specially adapted for particular parts of the body for the head or the neck
- A63B23/03—Exercising apparatus specially adapted for particular parts of the body for the head or the neck for face muscles
Definitions
- the invention belongs to the field of biomedicine technology, and specifically relates to a pharmaceutical composition for preventing and treating sequelae facial nerve paralysis and its application.
- Facial nerve palsy also known as facial neuritis, Bell's palsy, dysphagia, deviated mouth and eyes, etc.
- Facial nerve edema and/or myelin edema often occur in the early stage of pathology, and facial nerve injury Pressure or local circulation disorder may cause axonal degeneration in the late stage, most notably in the stylomastoid foramen and the facial nerve canal.
- facial nerve paralysis is divided into acute phase (within 15 days of onset), recovery phase (16 days to 6 months of onset), and sequelae phase (more than 6 months of onset).
- Familial facial palsy may be secondary to an autoimmune disorder involving inherited human leukocyte antigens.
- Abnormal anatomy of the facial nerve canal, stenosis of the facial nerve canal, and rapid changes in climate and temperature may all be risk factors for facial paralysis. Damage to different parts of the facial nerve (including preganglionic damage to the geniculate ganglion, damage to the geniculate ganglion, lesions near the stylomastoid foramen, etc.) causes different clinical symptoms.
- Facial nerve palsy includes central facial paralysis and peripheral facial paralysis. About 75% of patients with peripheral facial paralysis have idiopathic facial nerve palsy, and the causes of about 25% of patients include Guillain-Barré syndrome, Lyme neurospirosis, diabetic nerve damage, secondary facial nerve palsy, Traumatic facial paralysis, etc. Patients with severe facial nerve paralysis will develop severe facial nerve edema and high pressure within the nerve sheath in the early stages. The facial nerve will experience a vicious cycle of ischemia, hypoxia, and worsening edema, which may even lead to pathological changes such as nerve axon necrosis, disintegration, and demyelination. In the later stages of the patient's life, Dislocation regeneration causes facial joint movement.
- Treatment methods for facial nerve paralysis include medication (dehydration drugs or anti-edema drugs, antiviral drugs, B vitamins, glucocorticoids, etc.), acupuncture, physical therapy, facial rehabilitation training, etc. Mild and moderate patients can significantly improve their symptoms after 2 weeks to 2 months of treatment, with significant efficiency and clinical cure rates of 60%-70%, but exceeding More than 30% of moderate and severe patients have sequelae. Up to now, there is no effective clinical solution for treating the sequelae of facial nerve palsy.
- 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 the use of a pharmaceutical composition for preparing a medicine for preventing and treating facial nerve paralysis in the sequelae stage.
- the pharmaceutical composition for preventing and treating facial nerve paralysis in the sequelae stage is selected from the group consisting of mouse nerve growth factor and monosialic acid ganglion.
- Glycoside (GM1), cerebrospinalis carnosine, methylcobalamin, adenosylcobalamin, vitamin B complex, butylphthalide, cinpazide maleate, edaravone, edaravone dextrobornanol, cytophosphate Choline, Citicoline, Ganglioside, Oxiracetam, Piracetam, Aniracetam, Nerve Growth Factor, Citicoline, Neurotropin, Oryzanol, Vitamin B1, Vitamin B6 , any one or combination of vitamin B12, vitamin C, vitamin E, compound cerebroside, cerebroprotein, and nervonic acid.
- the pharmaceutical composition for preventing and treating sequelae facial nerve paralysis contains any one of mouse nerve growth factor, methylcobalamin, adenosine cobalt, or a combination thereof.
- the pharmaceutical composition for preventing and treating sequelae of facial nerve paralysis consists of a pharmaceutical composition for single oral administration and a pharmaceutical composition for single 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 mouse nerve growth factor. Any one of 30-90ug, methylcobalamin 0.5-1.0mg, adenosylcobalamin 0.1-0.5mg, dexamethasone 2-5mg or a 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 facial nerve paralysis in the sequelae stage Optionally used in conjunction 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 pharmaceutical composition for preventing and treating facial nerve paralysis in the sequelae stage.
- the pharmaceutical composition for preventing and treating facial nerve paralysis in the sequelae stage is selected from the group consisting of mouse nerve growth factor and monosialoganglioside (GM1).
- cerebrospinalis carnosine methylcobalamin, adenosylcobalamin, vitamin B complex, butylphthalide, cinepazide maleate, edaravone, edaravone dextroborneol, citicoline, citicoline Sodium choline, gangliosides, oxiracetam, piracetam, aniracetam, nerve growth factor, citicoline, neurotropin, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamins C. Any one or combination of vitamin E, compound cerebroside, cerebroprotein, and nervonic acid.
- the pharmaceutical composition for preventing and treating sequelae facial nerve paralysis contains any one of mouse nerve growth factor, methylcobalamin, adenosine cobalt, or a combination thereof.
- the pharmaceutical composition for preventing and treating sequelae of facial nerve paralysis consists of a pharmaceutical composition for single oral administration and a pharmaceutical composition for single 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 sequelae facial nerve 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 Rehabilitation exercise three Groups, each group trains 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 facial nerve paralysis in the sequelae stage.
- the treatment plan includes a pharmaceutical composition for preventing and treating facial nerve paralysis in the sequelae stage, optionally combined with any one of radiofrequency surgery, rehabilitation training exercises, or Use in combination.
- the pharmaceutical composition for preventing and treating sequelae facial nerve paralysis is selected from the group consisting of mouse nerve growth factor, monosialoganglioside (GM1), cerebrospinal carnosine, methylcobalamin, adenosylcobalamin, Vitamin B complex, butylphthalide, cinpazide maleate, edaravone, edaravone dexbornillol, citicoline, citicoline sodium, gangliosides, oxiracetam, Piracetam, aniracetam, nerve growth factor, citicoline, neurotropin, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin E, compound cerebroside, cerebroprotein , any one or combination thereof.
- GM1 monosialoganglioside
- cerebrospinal carnosine methylcobalamin
- adenosylcobalamin Vitamin B complex
- butylphthalide cinpazide maleate
- edaravone
- the pharmaceutical composition for preventing and treating sequelae facial nerve paralysis contains any one of mouse nerve growth factor, methylcobalamin, adenosine cobalt, or a combination thereof.
- the pharmaceutical composition for preventing and treating sequelae of facial nerve paralysis consists of a pharmaceutical composition for single oral administration and a pharmaceutical composition for single 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 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 sequelae facial nerve 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.
- 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 Place mesenchymal passaged stem cells with a density of 5.0 ⁇ 10 6 /mL-5.0 ⁇ 10 7 /mL in a 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 placed at 37.0°C ⁇ 0.5°C, 5% ⁇ 1.0 After culturing for 2h-6h under % CO 2 conditions, separate, wash, and collect the cells, wherein the stressor is selected from any one of compounds 1-16 or a combination thereof;
- 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 of physiological saline, 5% glucose solution, phosphate buffer (PBS), TBPS buffer, TBST buffer, and Tris buffer.
- PBS phosphate buffer
- TBPS buffer TBST buffer
- Tris buffer Tris buffer.
- 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 scientifically selects nerve repair drugs and configures them into a pharmaceutical composition for treating the sequelae of facial paralysis.
- Each component has synergistic effects.
- the pharmaceutical composition has a fast onset, prolonged duration of action, good therapeutic effect, and can reduce the use of a single drug. side effects.
- the radiofrequency method is used collaboratively to treat the sequelae of facial paralysis, which can quickly improve the symptoms of facial paralysis and accelerate the recovery process of the facial nerve. It 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:
- 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 for the sequelae of facial paralysis
- Group 1 10 patients
- Group 2 (30 patients)
- Group 3 20 patients
- Patient inclusion criteria Meet the diagnostic criteria of facial neuritis in traditional Chinese medicine and Western medicine, and the patient has onset for more than 6 months; age is 20-70 years old; H-B classification 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 injections are performed at Yangbai point, temple 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.
- 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.
- 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. 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.
- Group 1 One course of treatment for 7 days, repeated treatment for 4-6 courses, no complications and sequelae such as fever, allergies, aggravation of symptoms, etc., and more than 50% of patients' facial muscles improved.
- the effectiveness of treatment for 28 days is 70%.
- Group 2 The effective rate on the day of treatment was 70%, the effective rate was 50%, and the patient's postoperative satisfaction was 80%. There were no sequelae such as fever, allergies, or aggravation of symptoms. Repeat the treatment 2 to 3 times within 6 months, and the therapeutic effects will accumulate. The patients followed the doctor's instructions and paid attention to reducing or even avoiding the effects of staying up late, fatigue, external infections, colds and other factors. There was basically no recurrence and the quality of life was significantly improved.
- Group 3 The symptoms of sequelae of facial paralysis were significantly improved.
- the effective rate on the day of treatment was 95%, the effective rate was 90%, and the patient's postoperative satisfaction was 90%. All tested patients had no side effects or adverse events. The patients followed the doctor's instructions and paid attention to reducing or even avoiding the effects of staying up late, fatigue, external infections, colds and other factors. There was basically no recurrence and the quality of life was significantly improved.
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Abstract
The present invention relates to a pharmaceutical composition for preventing and treating sequelae stage facial nerve paralysis. The pharmaceutical composition is selected from one among or a combination of mouse nerve growth factor, monosialoganglioside (GM1), cerebroside carnosine, mecobalamine, and cobamamide, a B-complex vitamin, butylphthalide, cinepazide maleate, edaravone, edaravone and dexborneol, citicoline, citicoline sodium,a ganglioside, oxiracetam, a brain protein, piracetam, a nerve growth factor, citicoline, neurotropin, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin E, a compound brain peptide ganglioside, aniracetam, nervonic acid, or a nerve repairing cell protein extract or a nerve repairing protein composition having a repairing effect. The pharmaceutical of the present invention may be used in combination with a radio frequency operation or rehabilitative training.
Description
本发明属于生物医药技术领域，具体涉及用于防治后遗症期面神经麻痹的药物组合物及其应用。The invention belongs to the field of biomedicine technology, and specifically relates to a pharmaceutical composition for preventing and treating sequelae facial nerve paralysis and its application.
面神经麻痹(又称面神经炎、Bell麻痹、口僻、口眼歪斜等)为常见的面神经疾病(占比60％-75％)，其病理早期多发生面神经水肿和/或髓鞘水肿，面神经受压或局部循环障碍，晚期可出现轴索变性，并以茎乳孔及面神经管内部分最为显著。按照患者发病时长，将面神经麻痹其分为急性期(发病15天以内)、恢复期(发病16天至6个月)和后遗症期(发病超过6个月)。Facial nerve palsy (also known as facial neuritis, Bell's palsy, dysphagia, deviated mouth and eyes, etc.) is a common facial nerve disease (accounting for 60%-75%). Facial nerve edema and/or myelin edema often occur in the early stage of pathology, and facial nerve injury Pressure or local circulation disorder may cause axonal degeneration in the late stage, most notably in the stylomastoid foramen and the facial nerve canal. According to the duration of the patient's onset, facial nerve paralysis is divided into acute phase (within 15 days of onset), recovery phase (16 days to 6 months of onset), and sequelae phase (more than 6 months of onset).
面神经麻痹病因尚不明确。病毒感染(如潜伏的I型单纯疱疹病毒和带状疱疹病毒)及病毒感染后的重新激活被广泛接受。家族性面神经麻痹可能继发于遗传性人类白细胞抗原的自身免疫性疾病。面神经管解剖结构异常、面神经管狭窄、气候及温度的急剧变化等，均可能成为导致面瘫的危险因素。面神经的不同部位损害(包括膝状神经节前损害、膝状神经节损害、茎乳孔附近病变等)而表现不同的临床症状。面神经麻痹患者若恢复不彻底，常伴发瘫痪肌的萎缩、眼睑痉挛、连带运动、患侧面部牵拉感，且可能呈现病损后导致再生的神经纤维向邻近其他神经纤维通路生长，而支配原来属于其他神经纤维效应器所致的其他症状。The cause of facial nerve palsy is unknown. Viral infections (such as latent herpes simplex virus type I and herpes zoster virus) and their reactivation are widely accepted. Familial facial palsy may be secondary to an autoimmune disorder involving inherited human leukocyte antigens. Abnormal anatomy of the facial nerve canal, stenosis of the facial nerve canal, and rapid changes in climate and temperature may all be risk factors for facial paralysis. Damage to different parts of the facial nerve (including preganglionic damage to the geniculate ganglion, damage to the geniculate ganglion, lesions near the stylomastoid foramen, etc.) causes different clinical symptoms. If patients with facial nerve paralysis do not recover completely, they are often accompanied by atrophy of the paralyzed muscles, blepharospasm, joint movements, and a pulling sensation on the affected side of the face. In addition, the damage may cause the regenerated nerve fibers to grow to other adjacent nerve fiber pathways and innervate the facial nerve. Other symptoms that turned out to be caused by other nerve fiber effectors.
面神经麻痹包括中枢性面瘫和周围性面瘫。周围性面瘫中约有75％的患者为特发性面神经麻痹，约有25％患者的病因包括吉兰-巴雷综合征、莱姆神经螺旋体病、糖尿病性神经损害、继发性面神经麻痹、外伤性面瘫等。面神经麻痹重度患者早期出现严重面神经水肿，神经鞘膜内高压，面神经出现缺血、缺氧、水肿加重等恶性循环，甚至导致神经轴突坏死、崩解、脱髓鞘等病理改变，患者后期则错位再生而引起面部连带运动。Facial nerve palsy includes central facial paralysis and peripheral facial paralysis. About 75% of patients with peripheral facial paralysis have idiopathic facial nerve palsy, and the causes of about 25% of patients include Guillain-Barré syndrome, Lyme neurospirosis, diabetic nerve damage, secondary facial nerve palsy, Traumatic facial paralysis, etc. Patients with severe facial nerve paralysis will develop severe facial nerve edema and high pressure within the nerve sheath in the early stages. The facial nerve will experience a vicious cycle of ischemia, hypoxia, and worsening edema, which may even lead to pathological changes such as nerve axon necrosis, disintegration, and demyelination. In the later stages of the patient's life, Dislocation regeneration causes facial joint movement.
面神经麻痹的治疗方法包括药物(脱水药或去水肿药物、抗病毒药物、B族维生素、糖皮质激素等)治疗、针灸、理疗、面部康复训练等。轻度及中度患者经2周至2个月的治疗，明显改善症状，显效率和临床治愈率为60％-70％，但超
过30％的中度及重度患者存在后遗症。截至目前，临床尚没有用于治疗面神经麻痹后遗症的有效方案。Treatment methods for facial nerve paralysis include medication (dehydration drugs or anti-edema drugs, antiviral drugs, B vitamins, glucocorticoids, etc.), acupuncture, physical therapy, facial rehabilitation training, etc. Mild and moderate patients can significantly improve their symptoms after 2 weeks to 2 months of treatment, with significant efficiency and clinical cure rates of 60%-70%, but exceeding More than 30% of moderate and severe patients have sequelae. Up to now, there is no effective clinical solution for treating the sequelae of facial nerve palsy.
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用于一种药物组合物用于制备防治后遗症期面神经麻痹的药物中的应用，所述防治后遗症期面神经麻痹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、吡拉西坦、茴拉西坦、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、脑蛋白、神经酸的任一种或其组合。The object of the present invention is to provide the use of a pharmaceutical composition for preparing a medicine for preventing and treating facial nerve paralysis in the sequelae stage. The pharmaceutical composition for preventing and treating facial nerve paralysis in the sequelae stage is selected from the group consisting of mouse nerve growth factor and monosialic acid ganglion. Glycoside (GM1), cerebrospinalis carnosine, methylcobalamin, adenosylcobalamin, vitamin B complex, butylphthalide, cinpazide maleate, edaravone, edaravone dextrobornanol, cytophosphate Choline, Citicoline, Ganglioside, Oxiracetam, Piracetam, Aniracetam, Nerve Growth Factor, Citicoline, Neurotropin, Oryzanol, Vitamin B1, Vitamin B6 , any one or combination of vitamin B12, vitamin C, vitamin E, compound cerebroside, cerebroprotein, and nervonic acid.
本发明的优选技术方案中，所述防治后遗症期面神经麻痹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 sequelae facial nerve 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，所述用于防治后遗症面神经麻痹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 sequelae of facial nerve paralysis consists of a pharmaceutical composition for single oral administration and a pharmaceutical composition for single 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 mouse nerve growth factor. Any one of 30-90ug, methylcobalamin 0.5-1.0mg, adenosylcobalamin 0.1-0.5mg, dexamethasone 2-5mg 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，所述用于防治后遗症期面神经麻痹的药物组合物
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 facial nerve paralysis in the sequelae stage Optionally used in conjunction 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用于一种防治后遗症期面神经麻痹的药物组合物，所述防治后遗症期面神经麻痹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、吡拉西坦、茴拉西坦、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、脑蛋白、神经酸的任一种或其组合。
Another object of the present invention is to provide a pharmaceutical composition for preventing and treating facial nerve paralysis in the sequelae stage. The pharmaceutical composition for preventing and treating facial nerve paralysis in the sequelae stage is selected from the group consisting of mouse nerve growth factor and monosialoganglioside (GM1). , cerebrospinalis carnosine, methylcobalamin, adenosylcobalamin, vitamin B complex, butylphthalide, cinepazide maleate, edaravone, edaravone dextroborneol, citicoline, citicoline Sodium choline, gangliosides, oxiracetam, piracetam, aniracetam, nerve growth factor, citicoline, neurotropin, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamins C. Any one or combination of vitamin E, compound cerebroside, cerebroprotein, and nervonic acid.
本发明的优选技术方案中，所述防治后遗症期面神经麻痹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 sequelae facial nerve 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，所述用于防治后遗症面神经麻痹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 sequelae of facial nerve paralysis consists of a pharmaceutical composition for single oral administration and a pharmaceutical composition for single 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，所述用于防治后遗症期面神经麻痹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 sequelae facial nerve 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 Rehabilitation exercise three Groups, each group trains 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后遗症期面神经麻痹的治疗方案，所述治疗方案包括用于防治后遗症期面神经麻痹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 facial nerve paralysis in the sequelae stage. The treatment plan includes a pharmaceutical composition for preventing and treating facial nerve paralysis in the sequelae stage, optionally combined with any one of radiofrequency surgery, rehabilitation training exercises, or Use in combination.
本发明的优选技术方案中，所述防治后遗症期面神经麻痹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、吡拉西坦、茴拉西坦、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、脑蛋白、神经酸的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating sequelae facial nerve paralysis is selected from the group consisting of mouse nerve growth factor, monosialoganglioside (GM1), cerebrospinal carnosine, methylcobalamin, adenosylcobalamin, Vitamin B complex, butylphthalide, cinpazide maleate, edaravone, edaravone dexbornillol, citicoline, citicoline sodium, gangliosides, oxiracetam, Piracetam, aniracetam, nerve growth factor, citicoline, neurotropin, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin E, compound cerebroside, cerebroprotein , any one or combination thereof.
本发明的优选技术方案中，所述防治后遗症期面神经麻痹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 sequelae facial nerve 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，所述用于防治后遗症面神经麻痹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 sequelae of facial nerve paralysis consists of a pharmaceutical composition for single oral administration and a pharmaceutical composition for single 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 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，所述用于防治后遗症期面神经麻痹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 sequelae facial nerve 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.
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: Place mesenchymal passaged stem cells with a density of 5.0×10 6 /mL-5.0 ×10 7 /mL in a 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 2-10μmol/L stress medium, and then placed at 37.0℃±0.5℃, 5%±1.0 After culturing for 2h-6h under % CO 2 conditions, separate, wash, and collect the cells, wherein the stressor is selected from any one of compounds 1-16 or a combination thereof;
S-1: Place mesenchymal passaged stem cells with a density of 5.0×10 6 /mL-5.0 ×10 7 /mL in a 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 2-10μmol/L stress medium, and then placed at 37.0℃±0.5℃, 5%±1.0 After culturing for 2h-6h under % CO 2 conditions, separate, wash, and collect the cells, wherein 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 of physiological saline, 5% glucose solution, phosphate buffer (PBS), TBPS buffer, TBST buffer, and Tris buffer. One 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 cells, wash them with PBS, and add 0.25% trypsin for digestion for 2 minutes- After 3 minutes, add an equal volume of trypsin stop solution to stop digestion, gently pipette, centrifuge at 1200-1500 rpm/min*5-8 minutes, and collect the cells.
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、本发明科学筛选神经修复药物，配置成用于治疗面瘫后遗症的药物组合物，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。同时协同采用射频方法用于面瘫后遗症的治疗，可以快速改善面瘫症状，加速面神经的恢复过程，安全可靠，无明显的副作用和并发症。1. The present invention scientifically selects nerve repair drugs and configures them into a pharmaceutical composition for treating the sequelae of facial paralysis. Each component has synergistic effects. The pharmaceutical composition has a fast onset, prolonged duration of action, good therapeutic effect, and can reduce the use of a single drug. side effects. At the same time, the radiofrequency method is used collaboratively to treat the sequelae of facial paralysis, which can quickly improve the symptoms of facial paralysis and accelerate the recovery process of the facial nerve. It is safe and reliable, without obvious side effects and complications.
2、本发明能够节约药物使用量，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.
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 Wharton glue layer tissue, and cut it into small pieces of 3mm3 . Centrifuge, wash, collect the tissue pieces, place them in a culture bottle, add DMEM/F12 medium containing 10% fetal bovine serum FBS, 100ug/ml penicillin, and 100ug/ml streptomycin, and then place it at 37°C , culture under 5% CO 2 conditions to promote their adhesion. After every 2-3 days, observe that 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 off, collect the tissue blocks and low-layer cells respectively, and culture the collected tissue blocks again;
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 5μmol/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后遗期的治疗效果研究 Test Example 1 Study on the therapeutic effect of the pharmaceutical composition of the present invention for the sequelae of facial paralysis
选取面瘫后遗症期患者60名，分为1组(10名)、2组(30名)、3组(20名)。患者入组标准：符合面神经炎中医、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。60 patients with sequelae of facial paralysis were selected and divided into Group 1 (10 patients), Group 2 (30 patients), and Group 3 (20 patients). Patient inclusion criteria: Meet the diagnostic criteria of facial neuritis in traditional Chinese medicine and Western medicine, and the patient has onset for more than 6 months; age is 20-70 years old; H-B classification 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，3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, 3 times/day, every other month; adenosylcobalamin 0.5 mg/time, 3 times/day for 3 consecutive weeks, stop for 1 week, and then continue to take 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 injections are performed at Yangbai point, temple 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. 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.
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，3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, 3 times/day, every other month; adenosylcobalamin 0.5 mg/time, 3 times/day for 3 consecutive weeks, stop for 1 week, and then continue to take 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 are performed at Liao, Dicang, Jieche, the temple on the opposite side, Dicang, and Hegu points 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. 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.
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.
Efficacy evaluation: Satisfaction questionnaire and clinical rating House-Brakmann facial nerve function classification efficacy evaluation form.
1组：1个疗程7天，重复治疗4-6个疗程，无发热、过敏、症状加重等并发症和后遗症，超过50％的患者面部肌肉改善。治疗28天的有效率70％。Group 1: One course of treatment for 7 days, repeated treatment for 4-6 courses, no complications and sequelae such as fever, allergies, aggravation of symptoms, etc., and more than 50% of patients' facial muscles improved. The effectiveness of treatment for 28 days is 70%.
2组:治疗当天有效率为70％，显效率50％，患者术后满意度80％。无发热、过敏、症状加重等后遗症。6个月内重复治疗2～3次，疗效累积。患者遵照医嘱，注意减少甚至避免熬夜、疲劳、外部感染、受凉等因素的影响，基本无复发，生活质量显著提高。Group 2: The effective rate on the day of treatment was 70%, the effective rate was 50%, and the patient's postoperative satisfaction was 80%. There were no sequelae such as fever, allergies, or aggravation of symptoms. Repeat the treatment 2 to 3 times within 6 months, and the therapeutic effects will accumulate. The patients followed the doctor's instructions and paid attention to reducing or even avoiding the effects of staying up late, fatigue, external infections, colds and other factors. There was basically no recurrence and the quality of life was significantly improved.
3组：面瘫后遗症症状有明显改善。治疗当天有效率为95％，显效率90％，患者术后满意度90％。全部受试患者均无副作用和不良事件。患者遵照医嘱，注意减少甚至避免熬夜、疲劳、外部感染、受凉等因素的影响，基本无复发，生活质量显著提高。Group 3: The symptoms of sequelae of facial paralysis were significantly improved. The effective rate on the day of treatment was 95%, the effective rate was 90%, and the patient's postoperative satisfaction was 90%. All tested patients had no side effects or adverse events. The patients followed the doctor's instructions and paid attention to reducing or even avoiding the effects of staying up late, fatigue, external infections, colds and other factors. There was basically no recurrence and the quality of life was significantly improved.
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)
- 一种药物组合物用于制备防治后遗症期面神经麻痹的药物中的应用，所述防治后遗症期面神经麻痹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、吡拉西坦、茴拉西坦、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、脑蛋白、神经酸的任一种或其组合。The application of a pharmaceutical composition for preparing a medicine for preventing and treating facial nerve paralysis in the sequelae stage. The pharmaceutical composition for preventing and treating facial nerve paralysis in the sequelae stage is selected from the group consisting of mouse nerve growth factor, monosialoganglioside (GM1), and cerebroside. Carnosine, methylcobalamin, adenosylcobalamin, vitamin B complex, butylphthalide, cinipazide maleate, edaravone, edaravone dextrobornanol, citicoline, citicoline sodium , gangliosides, oxiracetam, piracetam, aniracetam, nerve growth factor, citicoline, neurotropin, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin E. Any one of compound cerebroside, cerebroprotein, and nervonic acid or their combination.
- 如权利要求1所述的应用，所述防治后遗症期面神经麻痹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。Application as claimed in claim 1, wherein the pharmaceutical composition for preventing and treating sequelae facial nerve paralysis contains any one of rat nerve growth factor, methylcobalamin, adenosine cobalt or a combination thereof.
- 如权利要求1-2任一项所述的应用，所述用于防治后遗症面神经麻痹的药物组合物由单次口服用的药物组合物和和单次穴位注射用的药物组合物组成。The application according to any one of claims 1 to 2, wherein the pharmaceutical composition for preventing and treating sequelae of facial nerve paralysis consists of a pharmaceutical composition for single oral administration and a pharmaceutical composition for single acupoint injection.
- 如权利要求1-3任一项所述的应用，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。According to the application according to any one of claims 1 to 3, the pharmaceutical composition for single administration contains any one of methylcobalamin 0.5-1.0 mg, adenosylcobalamin 0.1-0.5 mg, or a combination thereof.
- 如权利要求1-4任一项所述的应用，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；For the application according to any one of claims 1 to 4, 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, for 3 consecutive weeks, stop for 1 week, and then continue to repeat for half a year;
- 如权利要求1-5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 5, 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.
- 如权利要求1-6任一项所述的应用，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。For the application according to any one of claims 1 to 6, acupoint injection is 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.
- 如权利要求1-7任一项所述的应用，患所述用于防治后遗症期面神经麻痹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。According to the application according to any one of claims 1 to 7, the pharmaceutical composition for preventing and treating sequelae facial nerve paralysis is optionally used in combination with any one of radiofrequency surgery, rehabilitation training exercises, or a combination thereof.
- 如权利要求1-8任一项所述的防治后遗症期面神经麻痹的药物组合物，所述防治后遗症期面神经麻痹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、吡拉西坦、茴拉西坦、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、脑蛋白、神经酸的任一种或其组合。The pharmaceutical composition for preventing and treating facial nerve paralysis in the sequelae stage according to any one of claims 1 to 8, wherein the pharmaceutical composition for preventing and treating facial nerve paralysis in the sequelae stage is selected from the group consisting of mouse nerve growth factor and monosialoganglioside (GM1). , cerebrospinalis carnosine, methylcobalamin, adenosylcobalamin, vitamin B complex, butylphthalide, cinepazide maleate, edaravone, edaravone dextroborneol, citicoline, citicoline Sodium choline, gangliosides, oxiracetam, piracetam, aniracetam, nerve growth factor, citicoline, neurotropin, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamins C, Vitamin E, Compound Brain Peptide Any one of glycosides, cerebroproteins, and nervonic acids or a combination thereof.
- 一种防治后遗症期面神经麻痹的治疗方案，所述治疗方案包括用于如权利要求1-8任一项所述的防治后遗症期面神经麻痹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 facial nerve paralysis in the sequelae stage, the treatment plan includes a pharmaceutical composition for preventing and treating facial nerve paralysis in the sequelae stage as described in any one of claims 1-8, optionally combined with radiofrequency surgery and rehabilitation training exercises. Use any one or a combination thereof.
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| PCT/CN2023/117898 WO2024051846A1 (en) | 2022-09-09 | 2023-09-09 | Use of radio frequency apparatus in treatment of facial paralysis synkinesis |
| PCT/CN2023/117900 WO2024051848A1 (en) | 2022-09-09 | 2023-09-09 | Pharmaceutical composition for preventing and treating nervous system lesions and application thereof |
| PCT/CN2023/117894 WO2024051843A1 (en) | 2022-09-09 | 2023-09-09 | Pharmaceutical composition for preventing and treating convalescent stage facial nerve paralysis and use thereof |
| PCT/CN2023/117899 WO2024051847A1 (en) | 2022-09-09 | 2023-09-09 | Pharmaceutical composition for preventing and treating facial nerve micro-entrapment syndrome and use thereof |
| PCT/CN2023/117897 WO2024051845A1 (en) | 2022-09-09 | 2023-09-09 | Pharmaceutical composition for preventing and treating sequelae stage facial nerve paralysis, and use thereof |
| PCT/CN2023/117896 WO2024051844A1 (en) | 2022-09-09 | 2023-09-09 | Pharmaceutical composition for preventing and treating acute stage facial nerve paralysis and use thereof |
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| PCT/CN2023/117898 WO2024051846A1 (en) | 2022-09-09 | 2023-09-09 | Use of radio frequency apparatus in treatment of facial paralysis synkinesis |
| PCT/CN2023/117900 WO2024051848A1 (en) | 2022-09-09 | 2023-09-09 | Pharmaceutical composition for preventing and treating nervous system lesions and application thereof |
| PCT/CN2023/117894 WO2024051843A1 (en) | 2022-09-09 | 2023-09-09 | Pharmaceutical composition for preventing and treating convalescent stage facial nerve paralysis and use thereof |
| PCT/CN2023/117899 WO2024051847A1 (en) | 2022-09-09 | 2023-09-09 | Pharmaceutical composition for preventing and treating facial nerve micro-entrapment syndrome and use thereof |
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| CN117679649A (en) | 2024-03-12 |
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| WO2024051847A1 (en) | 2024-03-14 |
| CN117679519A (en) | 2024-03-12 |
| WO2024051846A1 (en) | 2024-03-14 |
| CN117679520A (en) | 2024-03-12 |
| WO2024051844A1 (en) | 2024-03-14 |
| CN117679522A (en) | 2024-03-12 |
| WO2024051848A1 (en) | 2024-03-14 |
| WO2024051843A1 (en) | 2024-03-14 |
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