WO2024051844A1 - Pharmaceutical composition for preventing and treating acute stage facial nerve paralysis and use thereof - Google Patents
Pharmaceutical composition for preventing and treating acute stage facial nerve paralysis and use thereof Download PDFInfo
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- WO2024051844A1 WO2024051844A1 PCT/CN2023/117896 CN2023117896W WO2024051844A1 WO 2024051844 A1 WO2024051844 A1 WO 2024051844A1 CN 2023117896 W CN2023117896 W CN 2023117896W WO 2024051844 A1 WO2024051844 A1 WO 2024051844A1
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Definitions
- the invention belongs to the technical field of biomedicine, and specifically relates to a pharmaceutical composition for preventing and treating acute phase facial nerve paralysis, its preparation method and its application.
- Facial nerve palsy also known as facial neuritis, Bell's palsy, dystonia, mouth and eye deviation, 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).
- 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 effective and clinical cure rates of 60%-70%. However, more than 30% of moderate and severe patients have sequelae. To date, there are no specific drugs for the treatment of acute facial nerve paralysis. For this reason, there is a need to develop pharmaceutical compositions that can safely and effectively treat facial nerve paralysis in the acute phase.
- 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 a pharmaceutical composition for preventing and treating acute phase facial nerve paralysis, which composition contains dehydration drugs, antiviral drugs, anti-inflammatory drugs, nerve repair drugs and/or blood improvement drugs. Any one or combination of circulating drugs.
- the dehydrating drug is selected from any one of mannitol, sorbitol, aescin, sodium aescin, 50% hypertonic glucose solution or a combination thereof.
- the antiviral drug is selected from the group consisting of acyclovir, valacyclovir, dibazole, Rhinoceros Jiedu, Virusin, favipiravir, Paxlovid, and monogravir (Molnupiravir), oseltamivir, remdesivir, remdesivir (GS-5734), indinavir, saquinavir, lopinavir, ritonavir (Ritonavir), a Zanavir, darunavir, tipranavir, flusanavir, enzatovir, pretovir, abacavir, elvitegravir, maribabavir, raltegravir, Any of bavirin, amantadine, oseltamivir, zanamivir, peramivir, lanamivir, ganciclovir, baloxavir, or nelfinavir or combination
- the anti-inflammatory drug is selected from dexamethasone, methylprednisolone, prednisolone, methylprednisolone (methylprednisolone), cortisone, hydrocortisone, prednisone, Prednisolone or any combination thereof.
- the nerve repair drugs and/or blood circulation improving drugs are selected from the group consisting of mouse nerve growth factor, monosialoganglioside (GM1), cerebrospinalis 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
- cerebrospinalis carnosine methylcobalamin
- adenosylcobalamin Vitamin B complex
- butylphthalide cinpazide maleate
- edaravone edar
- the pharmaceutical composition for preventing and treating acute phase facial nerve paralysis contains mannitol, sodium aescinate, acyclovir or valacyclovir, dexamethasone, prednisone, and cytophosphate Any one of sodium choline, ginkgo leaves, mouse nerve growth factor, methylcobalamin, adenosylcobalamin or a combination thereof.
- the pharmaceutical composition for preventing and treating acute facial nerve paralysis consists of a pharmaceutical composition for oral administration and a pharmaceutical composition for acupoint injection.
- the pharmaceutical composition for single oral administration contains 125-250 ml of mannitol, 0.5 mg of methylcobalamin, 5 mg of anti-inflammatory drugs, 30 mg of fasudil, 30 ug of mouse nerve growth factor, and 15 ml of ginkgo leaf extract.
- the anti-inflammatory drug is selected from any one of dexamethasone, sodium aescinate, methylprednisolone or a combination thereof.
- the dosage regimen of the oral pharmaceutical composition is:
- the pharmaceutical composition for single oral administration contains 125-250 ml of mannitol, 10-20 mg of sodium aescin, 0.3-0.4 g of acyclovir or valacyclovir, dexamethasone or prednisone.
- Disone tablets 1-5mg Citicoline sodium tablets 0.2-0.5mg, Ginkgo biloba leaves 0.1-0.2g, mouse nerve growth factor 30-90ug, methylcobalamin 0.5-1.0mg, adenosylcobalamin 0.1-0.5mg, Dexamethasone 2-5 mg of any one or combination thereof.
- the dosage regimen of the oral pharmaceutical composition is:
- Oral prednisone acetate tablets (5 mg/time, 2 times/day, for one week), followed by oral prednisone acetate tablets (5 mg/time, once/day, for one week);
- 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 composed of mouse nerve growth factor, methylcobalamin, and vitamin B1 in a mass ratio of 0.03:0.5:200.
- 30ug of mouse nerve growth factor, methylcobalamin 0.5 mg of amine and 200 mg of vitamin B1 are mixed into 5 ml of medicinal solution and then injected into the acupoint.
- the pharmaceutical composition for single acupoint injection contains any one of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 200mg of vitamin B 1 or a combination thereof.
- the pharmaceutical composition for a single acupoint injection consists of 30-90ug of mouse nerve growth factor, 0.5-1.0 mg of methylcobalamin, 0.1-0.5 mg of adenosylcobalamin, and 2-5 mg of dexamethasone.
- the pharmaceutical composition for single acupoint injection is composed of mouse nerve growth factor It consists of 30ug, methylcobalamin 0.5mg, adenosylcobalamin 0.5mg, dexamethasone 2mg and lidocaine hydrochloride 1ml, wherein the concentration of lidocaine hydrochloride is selected from any of 0.8%, 1%, 1.5% and 2%. A sort of.
- 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, 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.
- Another object of the present invention is to provide a pharmaceutical composition for use in the preparation of drugs for preventing and treating acute facial nerve paralysis, wherein the pharmaceutical composition for preventing and treating acute facial nerve paralysis contains dehydrating drugs and antiviral drugs. , any one or combination of anti-inflammatory drugs, nerve repair drugs and/or blood circulation improving drugs.
- the dehydrating drug is selected from any one of mannitol, sorbitol, aescin, sodium aescin, 50% hypertonic glucose solution or a combination thereof.
- the antiviral drug is selected from the group consisting of acyclovir, valacyclovir, diba Azole, Rhinoceros Jiedu, Virusin, favipiravir, Paxlovid, Molnupiravir, Oseltamivir, Remdesivir, Remdesivir (GS-5734), Indene Dinavir, saquinavir, lopinavir, ritonavir (Ritonavir), atazanavir, darunavir, tipranavir, flusanavir, enzatovir, pritovir Abacavir, elvitegravir, maribavirin, raltegravir, ribavirin, amantadine, oseltamivir, zanamivir, peramivir, lanimivir Any one of ganciclovir, baloxavir, nelfinavir or a combination thereof.
- the anti-inflammatory drug is selected from dexamethasone, methylprednisolone, prednisolone, methylprednisolone (methylprednisolone), cortisone, hydrocortisone, prednisone, Prednisolone or any combination thereof.
- the nerve repair drugs and/or blood circulation improving drugs are selected from the group consisting of mouse nerve growth factor, monosialoganglioside (GM1), cerebrospinalis 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
- cerebrospinalis carnosine methylcobalamin
- adenosylcobalamin Vitamin B complex
- butylphthalide cinpazide maleate
- edaravone edar
- the pharmaceutical composition for preventing and treating acute phase facial nerve paralysis contains mannitol, sodium aescinate, acyclovir or valacyclovir, dexamethasone, prednisone, and cytophosphate Any one of sodium choline, ginkgo leaves, mouse nerve growth factor, methylcobalamin, adenosylcobalamin or a combination thereof.
- the pharmaceutical composition for preventing and treating acute facial nerve paralysis consists of a pharmaceutical composition for oral administration and a pharmaceutical composition for acupoint injection.
- the pharmaceutical composition for single oral administration contains 125-250 ml of mannitol, 0.5 mg of methylcobalamin, 5 mg of anti-inflammatory drugs, 30 mg of fasudil, 30 ug of mouse nerve growth factor, and 15 ml of ginkgo leaf extract.
- the anti-inflammatory drug is selected from any one of dexamethasone, sodium aescinate, methylprednisolone or a combination thereof.
- the dosage regimen of the oral pharmaceutical composition is:
- the pharmaceutical composition for single oral administration contains 125-250 ml of mannitol, 10-20 mg of sodium aescin, 0.3-0.4 g of acyclovir or valacyclovir, dexamethasone or prednisone.
- Disone tablets 1-5mg Citicoline sodium tablets 0.2-0.5mg, Ginkgo biloba leaves 0.1-0.2g, mouse nerve growth factor 30-90ug, methylcobalamin 0.5-1.0mg, adenosylcobalamin 0.1-0.5mg, Dexamethasone 2-5 mg of any one or combination thereof.
- the dosage regimen of the oral pharmaceutical composition is:
- Oral prednisone acetate tablets (5 mg/time, 2 times/day, for one week), followed by oral prednisone acetate tablets (5 mg/time, once/day, for one week);
- 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 composed of mouse nerve growth factor, methylcobalamin, and vitamin B1 in a mass ratio of 0.03:0.5:200.
- 30ug of mouse nerve growth factor, methylcobalamin 0.5 mg of amine and 200 mg of vitamin B1 are mixed into 5 ml of medicinal solution and then injected into the acupoint.
- the pharmaceutical composition for single acupoint injection contains any one of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 200mg of vitamin B 1 or a combination thereof.
- the pharmaceutical composition for a single acupoint injection consists of 30-90ug of mouse nerve growth factor, 0.5-1.0 mg of methylcobalamin, 0.1-0.5 mg of adenosylcobalamin, and 2-5 mg of dexamethasone.
- the pharmaceutical composition for a 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.
- 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, 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 a single acupoint injection is injected once a day into the acupoint, and the treatment course is 7 days.
- each acupoint injection treatment lasts for 2-6 courses, preferably 4-5 courses.
- Another object of the present invention is to provide a treatment plan for treating acute phase facial nerve paralysis.
- the treatment plan includes using the pharmaceutical composition for preventing and treating acute phase facial nerve paralysis of the present invention.
- the pharmaceutical composition for paralysis contains any one or a combination of dehydration drugs, antiviral drugs, anti-inflammatory drugs, nerve repair drugs and/or blood circulation improving drugs.
- the dehydrating drug is selected from any one of mannitol, sorbitol, aescin, sodium aescin, 50% hypertonic glucose solution or a combination thereof.
- the antiviral drug is selected from the group consisting of acyclovir, valacyclovir, dibazole, Rhinoceros Jiedu, Virusin, favipiravir, Paxlovid, and monogravir (Molnupiravir), oseltamivir, remdesivir, remdesivir (GS-5734), indinavir, saquinavir, lopinavir, ritonavir (Ritonavir), a Zanavir, darunavir, tipranavir, flusanavir, enzatovir, pretovir, abacavir, elvitegravir, maribabavir, Raltegravir, ribavirin, amantadine, oseltamivir, zanamivir, peramivir, lanamivir, ganciclovir, baloxavir, nefir Any one or combination of acyclovir, valacycl
- the anti-inflammatory drug is selected from dexamethasone, methylprednisolone, prednisolone, methylprednisolone (methylprednisolone), cortisone, hydrocortisone, prednisone, Prednisolone or any combination thereof.
- the nerve repair drugs and/or blood circulation improving drugs are selected from the group consisting of mouse nerve growth factor, monosialoganglioside (GM1), cerebrospinalis 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
- cerebrospinalis carnosine methylcobalamin
- adenosylcobalamin Vitamin B complex
- butylphthalide cinpazide maleate
- edaravone edar
- the pharmaceutical composition for preventing and treating acute phase facial nerve paralysis contains mannitol, sodium aescinate, acyclovir or valacyclovir, dexamethasone, prednisone, and cytophosphate Any one of sodium choline, ginkgo leaves, mouse nerve growth factor, methylcobalamin, adenosylcobalamin or a combination thereof.
- the pharmaceutical composition for preventing and treating acute facial nerve paralysis consists of a pharmaceutical composition for oral administration and a pharmaceutical composition for acupoint injection.
- the pharmaceutical composition for single oral administration contains 125-250 ml of mannitol, 0.5 mg of methylcobalamin, 5 mg of anti-inflammatory drugs, 30 mg of fasudil, 30 ug of mouse nerve growth factor, and 15 ml of ginkgo leaf extract.
- the anti-inflammatory drug is selected from any one of dexamethasone, sodium aescinate, methylprednisolone or a combination thereof.
- the dosage regimen of the oral pharmaceutical composition is:
- the pharmaceutical composition for single oral administration contains 125-250 ml of mannitol, 10-20 mg of sodium aescin, 0.3-0.4 g of acyclovir or valacyclovir, dexamethasone or prednisone.
- Dipine tablets 1-5mg Citicoline sodium tablets 0.2-0.5mg, Ginkgo biloba leaves 0.1-0.2g, mouse nerve growth factor 30-90ug, methylcobalamin 0.5-1.0mg, adenosylcobalamin 0.1-0.5mg, dexamethasone 2-5mg any one or combination thereof.
- the dosage regimen of the oral pharmaceutical composition is:
- Oral prednisone acetate tablets (5 mg/time, 2 times/day, for one week), followed by oral prednisone acetate tablets (5 mg/time, once/day, for one week);
- 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 composed of mouse nerve growth factor, methylcobalamin, and vitamin B1 in a mass ratio of 0.03:0.5:200.
- 30ug of mouse nerve growth factor, methylcobalamin 0.5 mg of amine and 200 mg of vitamin B1 are mixed into 5 ml of medicinal solution and then injected into the acupoint.
- the pharmaceutical composition for single acupoint injection contains any one of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 200mg of vitamin B 1 or a combination thereof.
- the pharmaceutical composition for a single acupoint injection consists of 30-90ug of mouse nerve growth factor, 0.5-1.0 mg of methylcobalamin, 0.1-0.5 mg of adenosylcobalamin, and 2-5 mg of dexamethasone.
- the pharmaceutical composition for a 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, 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 nerve repair cell protein extract or nerve repair cell protein composition with repair effect described in the present invention is prepared with reference to patent applications (CN2023100429139, PCT/CN2023/073566, CN2023100429143, PCT/CN2023/073582). have to.
- the preparation method of the nerve repair cell protein extract with nerve repair effect includes the following steps:
- S-1 Mesenchymal passaged stem cells with a density of 5.0 ⁇ 10 6 /mL-5.0 ⁇ 10 7 /mL were placed in DMEM/F12 40-50%, RPMI1640 40-50%, bovine serum albumin (BSA) )0.1-2%, epidermal growth factor (EGF) 1-15ug/mL, fibroblast growth factor (FGF) 1-15ug/mL, insulin transferrin 1-15ug/mL, compound amino acid (18AA) 0.01- 0.1% and 2-10 ⁇ mol/L stress medium, and then culture it at 37.0°C ⁇ 0.5°C, 5% ⁇ 1.0% CO2 for 2h-6h, separate, wash and collect the cells, where , the stressor is selected from any one of compounds 1-16 or a combination thereof;
- BSA bovine serum albumin
- S-2 Disperse the collected cells in the solvent at a density of 5.0 ⁇ 10 6 /mL-5.0 ⁇ 10 7 /mL, and then place them at 2°C-8°C for ultrasonic treatment to prepare a cell lysis solution , wherein the solvent is selected from any one selected from physiological saline, 5% glucose solution, phosphate buffered saline (PBS), TBPS buffer, TBST buffer, Tris buffer or a combination thereof;
- PBS phosphate buffered saline
- TBPS buffer TBST buffer
- Tris buffer Tris buffer
- step S-3 After separating the cell lysate prepared in step S-2, the obtained separation liquid is filtered through 0.45um and 0.22um filters in sequence.
- the culture medium of step S-1 contains DMEM/F12 42-45%, RPMI1640 42-45%, bovine serum albumin (BSA) 0.5-1.5%, epidermal cell growth factor (EGF) 5 -10ug/mL, fibroblast growth factor (FGF) 5-10ug/mL, insulin transferrin 5-10ug/mL, compound amino acid (18AA) 0.02-0.05% and 3-8 ⁇ mol/L stressors.
- BSA bovine serum albumin
- the culture medium of step S-1 contains DMEM/F12 45%, RPMI1640 45%, bovine serum albumin (BSA) 0.5%, epidermal growth factor (EGF) 10ug/mL, fibroblasts Growth factor (FGF) 10ug/mL, insulin transferrin 10ug/mL, compound amino acid (18AA) 0.05% and 4-6 ⁇ mol/L stressors.
- BSA bovine serum albumin
- the density of mesenchymal passage stem cells in step S-1 is 8.0 ⁇ 10 6 -2.0 ⁇ 10 7 cells/mL, preferably 8.0 ⁇ 10 6 -1.0 ⁇ 10 7 cells/mL.
- the mesenchymal passage stem cells in step S-1 are cultured in the culture medium for 3h-5h, preferably 3.5h-4.5h.
- the solvent for washing cells in step S-1 is selected from any one of physiological saline, 5% glucose solution, phosphate buffer (PBS), TBPS buffer, TBST buffer, and Tris buffer. Or a combination thereof, the number of cell washings is 2-5 times, preferably 3-4 times.
- the separation described in step S-1 is selected from any one of centrifugation, filtration or a combination thereof, wherein the centrifugation conditions are 1000-2000rpm*3-15min, preferably 1200rpm-1500rpm* 5-10min.
- the ultrasonic conditions of step S-2 are: working at 2°C-8°C, 25kHZ, 360W for 3 seconds, followed by a gap of 1 second, and ultrasonic treatment for 1-5 minutes.
- the separation described in step S-3 is selected from any one of 2000-8000rpm*10-30min centrifugation, multi-stage centrifugation, multi-stage filtration or a combination thereof, preferably 3000-7000rpm*15-25min .
- the multi-stage centrifugation in step S-3 is 3000-4000rpm*3-5min, 5000-6000rpm*3-5min and 7000rpm*5-8min.
- the filter membrane pore size of the multi-stage filtration is selected from any one of 80um, 50um, 30um, 10um, and 5um.
- the cell protein extract prepared in step S-3 is frozen and stored, preferably at -40°C to -20°C.
- the cell protein extract prepared in step S-3 is enzymatically hydrolyzed by either a nuclease or a totipotent nuclease and then separated and purified.
- the culture of mesenchymal passaged stem cells or the culture of primary mesenchymal stem cells adopts the culture methods in this field.
- the culture of mesenchymal passage stem cells includes the following steps: adding primary mesenchymal stem cells to the passage medium at an initial density of 5.0 ⁇ 10 5 -5.0 ⁇ 10 6 /ml. , and then place it in the culture medium at 37.0°C ⁇ 0.5°C and 5% ⁇ 1.0% CO2 for 10-15 days. Every 2-3 days, after observing that the subculture medium turns yellow, replace half of the subculture medium. , the subculture medium contains DMEM/F12 medium with 10% FBS, 100 U/ml penicillin and 100ug/ml streptomycin.
- the culture of primary mesenchymal stem cells includes the following steps:
- the percentages are volume/volume percentages; when the present invention relates to the percentages between liquids and solids, the percentages are volume/volume percentages. / weight percentage; when the present invention relates to the percentage between solid and liquid, the percentage is weight/volume percentage; the rest is weight/weight percentage.
- This invention locates and selects acupoints in accordance with the acupoints specified in 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 clinical score uses the House-Brakmann facial nerve function grading efficacy evaluation form.
- the present invention has the following beneficial effects:
- the present invention scientifically combines marketed drugs for the treatment of acute phase facial paralysis, and adopts simultaneous administration and/or sequential administration to treat the affected side, which is beneficial to reducing edema in early stage facial paralysis, eliminating inflammation in the facial paralysis area, nourishing and repairing nerves damaged by facial paralysis. Damage myelin and axons.
- the dehydration drugs in the pharmaceutical composition are used to eliminate edema of facial paralysis in the acute phase, reduce or even eliminate facial nerve damage caused by acute edema, which is beneficial to the treatment, rehabilitation and prognosis of facial paralysis in the acute phase; the antiviral drugs are used to fight viruses and eliminate the causes of facial paralysis.
- anti-inflammatory drugs are used to remove inflammatory factors of facial paralysis, which is beneficial to the removal of inflammation and edema in facial paralysis, and is beneficial to the treatment, rehabilitation and prognosis of facial paralysis in the acute phase; nerve repair drugs and/or drugs to improve blood circulation It is used to improve blood circulation disorders caused by facial paralysis edema, viruses, inflammation, etc., and repair facial nerve damage caused by facial paralysis edema, viruses, inflammation, etc., which is beneficial to the treatment, rehabilitation and prognosis of facial paralysis in the acute phase.
- the present invention uses acupoint injection to deliver any one or a combination of nerve repair drugs, blood circulation improving drugs, neurotrophic drugs, anti-inflammatory drugs, antiviral drugs, using acupoints to achieve precise treatment and scientific treatment, improve curative effect and Reduce the incidence of sequelae, reduce medication dosage, reduce facial disability rate, significantly improve treatment efficiency and reduce or even avoid side effects. It has the characteristics of quick onset, improved recovery rate, reduced recurrence rate, reduced treatment pain, shortened treatment cycle, no adverse reactions, etc. Advantages: Reduce patient treatment burden and national medical insurance burden.
- 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 acute facial paralysis
- Group 1 60 patients in the acute phase were selected and divided into group 1 (10 patients), group 2 (40 patients), and group 3 (10 patients).
- Patient inclusion criteria Meet the diagnostic criteria of facial neuritis in traditional Chinese medicine and Western medicine. Patients are all unilateral acute onset, with obvious symptoms appearing within a few hours or 1-3 days; 20-70 years old; onset within 15 days; H-B grade above level II ; Informed consent to accept this trial; patients with good compliance, non-coma, first onset of illness or previous history of facial paralysis, but no sequelae.
- Contraindications Those with complete rupture or loss of the facial nerve; those with infection or skin damage at the injection site; those who are pregnant or breastfeeding, as it may affect the health of the fetus or baby; those who are allergic to drugs, which may cause allergic reactions or other adverse reactions; those with mental disorders or Those who are unable to cooperate with rehabilitation or corrective training.
- the treatment plan of Group 1 (7 days each, 4 courses of treatment) included oral administration and acupoint injection.
- Acupoint injection administration plan :
- the pharmaceutical composition for a single acupoint injection is composed of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, and 200mg of vitamin B1. It is formulated into 5ml of medicinal solution for immediate use. Select the Yangbai point, temple, and four white points on the affected side of the face. Acupoint injections are performed at the acupoint, Yingxiang acupoint, Juliao acupoint, Dicang acupoint and Jieche acupoint, once a day.
- the treatment plan for the 2 groups (7 days each, 4 courses of treatment) included oral administration and acupoint injection.
- Oral prednisone acetate tablets (5 mg/time, 2 times/day, for one week), followed by oral prednisone acetate tablets (5 mg/time, once/day, for one week);
- Acupoint injection administration plan :
- the pharmaceutical composition for a single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride.
- Acupoint injection is performed at Yangbai point, Taiyang point, Sibai point, Yingxiang point, Juliiao point, Dicang point and Jieche point, once a day.
- the treatment plan for the 3 groups (7 days each, 4 courses of treatment) included oral administration and acupoint injection.
- Oral prednisone acetate tablets (5 mg/time, 2 times/day, for one week), followed by oral prednisone acetate tablets (5 mg/time, once/day, for one week);
- Acupoint injection administration plan :
- 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.
- Group 1 It takes effect on the same day of treatment, and more than 70% of patients have significant relief of ear pain, more than 40% of patients have improved facial muscles, and their mouths are not crooked and their faces are not rigid.
- the effective rate after 7 days of treatment is 70% and the effective rate is 40%.
- the effective rate of treatment for 15 days is 80%, and the effective rate is 70%.
- the recovery rate within 30 days of treatment exceeds 80%.
- Group 2 It takes effect on the same day of treatment, and more than 80% of patients have significant relief of ear pain, and more than 50% of patients have improved facial muscles, with their mouths crooked and their faces no longer rigid.
- the effective rate after 7 days of treatment is 80% and the effective rate is 50%.
- the effective rate of treatment for 15 days is 90%, and the effect is 80%.
- the recovery rate after 30 days of treatment is over 90%, with basically no sequelae, and the satisfaction score is 100 points.
- Patients who have not recovered can basically recover after continuing to take medication for 1-3 courses based on the patient's condition and medication history. 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.
- Test Group 3 The effect is faster and the improvement effect on facial muscle stiffness is more obvious. It takes effect on the same day of treatment, and more than 90% of patients have significant relief of ear pain, and more than 60% of patients have improved facial muscles, with their mouths crooked and their faces no longer rigid.
- the effective rate after 7 days of treatment is 90% and the effective rate is 70%. 90% effective after 15 days of treatment.
- the recovery rate within 30 days of treatment was 100%, with basically no sequelae, and the satisfaction score was 100 points.
- 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.
Abstract
The present invention relates to a pharmaceutical composition for preventing and treating acute stage facial nerve paralysis, the composition comprising any one among or a combination of an osmotic diuretic drug, an antiviral drug, an anti-inflammatory drug, a nerve repair drug, and/or a drug for improving blood circulation. The pharmaceutical composition of the present invention facilitates ameliorating early stage facial paralysis edema, eliminating inflammation at a facial paralysis site, providing nutrition to a damaged nerve and repairing and damaging the myelin sheath and axon, and performing targeted localization and administration; same remarkably improves a therapeutic effect and reduces or even eliminates side effects, and possesses advantages such as quick onset, improvement of the rate of remission, reduction of the rate of recurrence, reduction of drug dosage, relief from treatment-related pain, shortening of the treatment period, and being free from adverse reactions.
Description
本发明属于生物医药技术领域，具体涉及一种用于防治急性期面神经麻痹的药物组合物及其制备方法和其应用。The invention belongs to the technical field of biomedicine, and specifically relates to a pharmaceutical composition for preventing and treating acute phase facial nerve paralysis, its preparation method 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, dystonia, mouth and eye deviation, 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).
已有研究表明，面神经麻痹的发病率为11.5-53.3人/10万人，复发率为2.6％-15.2％，患者集中为20-40岁的男性，其主要临床表现包括面部自主运动、表情功能减退或丧失，面神经和面部表情肌组织营养障碍等，并影响患者容貌、个人尊严和社会形象，严重者甚至导致患者心理障碍、抑郁焦虑等病症。Studies have shown that the incidence rate of facial nerve paralysis is 11.5-53.3 people/100,000 people, and the recurrence rate is 2.6%-15.2%. The patients are concentrated in men aged 20-40 years old. Its main clinical manifestations include autonomous facial movement and expression function. Decrease or loss, facial nerve and facial expression musculature dystrophy, etc., and affect the patient's appearance, personal dignity and social image. In severe cases, it may even lead to psychological disorders, depression and anxiety in patients.
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。迄今，尚未用于治疗急性期面神经麻痹的特效药物。为此，需要开发安全有效地治疗急性期面神经麻痹的药物组合物。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 effective and clinical cure rates of 60%-70%. However, more than 30% of moderate and severe patients have sequelae. To date, there are no specific drugs for the treatment of acute facial nerve paralysis. For this reason, there is a need to develop pharmaceutical compositions that can safely and effectively treat facial nerve paralysis in the acute phase.
专利申请(CN2023100429139、PCT/CN2023/073566、CN2023100429143、PCT/CN2023/073582)公开了有关具有修复功效的神经修复蛋白提取物及神经修复蛋白组合物的技术内容，前述申请及内容作为本申请必不可少的技术参考和组成部分。Patent applications (CN2023100429139, PCT/CN2023/073566, CN2023100429143, PCT/CN2023/073582) disclose technical content related to nerve repair protein extracts and nerve repair protein compositions with repair effects. The aforementioned applications and contents are essential to this application. Few technical references and components.
发明内容Contents of the invention
本发明的目的在于提供一种用于防治急性期面神经麻痹的药物组合物，所述组合物含有脱水类药物、抗病毒药物、消炎药物、神经修复药物和/或改善血液
循环药物的任一种或其组合。The object of the present invention is to provide a pharmaceutical composition for preventing and treating acute phase facial nerve paralysis, which composition contains dehydration drugs, antiviral drugs, anti-inflammatory drugs, nerve repair drugs and/or blood improvement drugs. Any one or combination of circulating drugs.
本发明的优选技术方案中，所述脱水类药物选自甘露醇、山梨醇、七叶皂苷、七叶皂苷钠、50％的高渗葡萄糖溶液的任一种或其组合。In the preferred technical solution of the present invention, the dehydrating drug is selected from any one of mannitol, sorbitol, aescin, sodium aescin, 50% hypertonic glucose solution or a combination thereof.
本发明的优选技术方案中，所述抗病毒药物选自阿昔洛韦、伐昔洛韦、地巴唑、犀羚解毒、病毒灵、法匹拉韦(favipiravir)、Paxlovid、莫诺拉韦(Molnupiravir)、奥司他韦、雷米迪维、伦地西韦(Remdesivir，GS-5734)、茚地那韦、沙奎那韦、洛匹那韦、利托那韦(Ritonavir)、阿扎那韦、达芦那韦、替拉那韦、氟沙那韦、恩扎托韦、普瑞托韦、阿巴卡韦、埃替格韦、马立巴韦、雷特格韦、利巴韦林、金刚烷乙胺、奥司他韦、扎那米韦、帕拉米韦、拉尼米韦、更昔洛韦、巴洛沙韦(Baloxavir)、奈非那韦的任一种或其组合。In the preferred technical solution of the present invention, the antiviral drug is selected from the group consisting of acyclovir, valacyclovir, dibazole, Rhinoceros Jiedu, Virusin, favipiravir, Paxlovid, and monogravir (Molnupiravir), oseltamivir, remdesivir, remdesivir (GS-5734), indinavir, saquinavir, lopinavir, ritonavir (Ritonavir), a Zanavir, darunavir, tipranavir, flusanavir, enzatovir, pretovir, abacavir, elvitegravir, maribabavir, raltegravir, Any of bavirin, amantadine, oseltamivir, zanamivir, peramivir, lanamivir, ganciclovir, baloxavir, or nelfinavir or combination thereof.
本发明的优选技术方案中，所述消炎药物选自地塞米松、甲基强的松龙、强力松、甲强龙(甲泼尼龙)、可的松、氢化可的松、泼尼松、泼尼松龙的任一种或其组合。In the preferred technical solution of the present invention, the anti-inflammatory drug is selected from dexamethasone, methylprednisolone, prednisolone, methylprednisolone (methylprednisolone), cortisone, hydrocortisone, prednisone, Prednisolone or any combination thereof.
本发明的优选技术方案中，所述神经修复药物和/改善血液循环药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 nerve repair drugs and/or blood circulation improving drugs are selected from the group consisting of mouse nerve growth factor, monosialoganglioside (GM1), cerebrospinalis 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，所述用于防治急性期面神经麻痹的药物组合物含有甘露醇、七叶皂苷钠、阿昔洛韦或伐昔洛韦、地塞米松、强的松、胞磷胆碱钠、银杏叶片、鼠神经生长因子、甲钴胺、腺苷钴胺的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating acute phase facial nerve paralysis contains mannitol, sodium aescinate, acyclovir or valacyclovir, dexamethasone, prednisone, and cytophosphate Any one of sodium choline, ginkgo leaves, mouse nerve growth factor, methylcobalamin, adenosylcobalamin or a combination thereof.
本发明的优选技术方案中，所述用于防治急性期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。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating acute facial nerve paralysis consists of a pharmaceutical composition for oral administration and a pharmaceutical composition for acupoint injection.
本发明的优选技术方案中，单次口服用的药物组合物含有甘露醇125-250ml、甲钴胺0.5mg、消炎药物5mg、法舒地尔30mg、鼠神经生长因子30ug、银杏叶提取物15ml，所述的消炎药物选自地塞米松、七叶皂苷钠、甲强龙的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for single oral administration contains 125-250 ml of mannitol, 0.5 mg of methylcobalamin, 5 mg of anti-inflammatory drugs, 30 mg of fasudil, 30 ug of mouse nerve growth factor, and 15 ml of ginkgo leaf extract. , the anti-inflammatory drug is selected from any one of dexamethasone, sodium aescinate, methylprednisolone 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：
In the preferred technical solution of the present invention, the dosage regimen of the oral pharmaceutical composition is:
(1)静脉注射脱水剂甘露醇125-250ml，2次/日；(1) Intravenous injection of the dehydrating agent mannitol 125-250ml, 2 times/day;
(2)肌肉注射1次0.5mg的甲钴胺，每隔1日1次；(2) Inject 0.5 mg of methylcobalamin intramuscularly once every other day;
(3)静脉注射5mg的地塞米松，2次/日；(3) Intravenous injection of 5 mg of dexamethasone, 2 times/day;
(4)静脉注射法舒地尔，30mg/次，2次/日；(4) Intravenous injection of fasudil, 30 mg/time, 2 times/day;
(5)肌肉注射鼠神经生长因子30ug/次，1次/日；(5) Intramuscular injection of rat nerve growth factor 30ug/time, once/day;
(6)静脉注射银杏叶提取物15ml/次，1次/日。(6) Intravenous injection of Ginkgo leaf extract 15ml/time, once/day.
本发明的优选技术方案中，单次口服用的药物组合物含有甘露醇125-250ml、七叶皂苷钠10-20mg、阿昔洛韦或伐昔洛韦0.3-0.4g、地塞米松或强的松片1-5mg、胞磷胆碱钠片0.2-0.5mg、银杏叶片0.1-0.2g、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 oral administration contains 125-250 ml of mannitol, 10-20 mg of sodium aescin, 0.3-0.4 g of acyclovir or valacyclovir, dexamethasone or prednisone. Disone tablets 1-5mg, Citicoline sodium tablets 0.2-0.5mg, Ginkgo biloba leaves 0.1-0.2g, mouse nerve growth factor 30-90ug, methylcobalamin 0.5-1.0mg, adenosylcobalamin 0.1-0.5mg, Dexamethasone 2-5 mg of any one or 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：In the preferred technical solution of the present invention, the dosage regimen of the oral pharmaceutical composition is:
(1)静脉注射甘露醇(125-250ml/次，1-2次/天)和七叶皂苷钠(20mg/次，1-2次/天)，用药7-14天；(1) Intravenous injection of mannitol (125-250ml/time, 1-2 times/day) and sodium aescinate (20mg/time, 1-2 times/day) for 7-14 days;
(2)静脉注射阿昔洛韦或伐昔洛韦0.3g/次，2次/天，用药7-14天；(2) Intravenous injection of acyclovir or valacyclovir 0.3g/time, 2 times/day, for 7-14 days;
(3)静脉注射地塞米松(5-10mg/天，用药7-10天)；(3) Intravenous injection of dexamethasone (5-10mg/day, 7-10 days of medication);
(4)口服胞磷胆碱钠片(0.2g/次，3次/天，服用2-3周)和银杏叶片(0.1-0.2g/次，3次/天，服用2周)；(4) Oral administration of Citicoline sodium tablets (0.2g/time, 3 times/day, for 2-3 weeks) and Ginkgo biloba leaves (0.1-0.2g/time, 3 times/day, for 2 weeks);
(5)口服醋酸强的松片(5mg/次，2次/天，用药一周)后，口服醋酸强的松片(5mg/次，1次/天，用药一周)；(5) Oral prednisone acetate tablets (5 mg/time, 2 times/day, for one week), followed by oral prednisone acetate tablets (5 mg/time, once/day, for one week);
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由鼠神经生长因子、甲钴胺、维生素B1按照质量比为0.03:0.5:200组成，优选将鼠神经生长因子30ug、甲钴胺0.5mg、维生素B1 200mg配置成5ml药液后,穴位注射。In the preferred technical solution of the present invention, the pharmaceutical composition for a single acupoint injection is composed of mouse nerve growth factor, methylcobalamin, and vitamin B1 in a mass ratio of 0.03:0.5:200. Preferably, 30ug of mouse nerve growth factor, methylcobalamin 0.5 mg of amine and 200 mg of vitamin B1 are mixed into 5 ml of medicinal solution and then injected into the acupoint.
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30ug、甲钴胺0.5mg、维生素B1 200mg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 any one of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 200mg of vitamin B 1 or a combination thereof.
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30-90ug、甲钴胺0.5-1.0mg、腺苷钴胺0.1-0.5mg，地塞米松2-5mg组成。In the preferred technical solution of the present invention, the pharmaceutical composition for a single acupoint injection consists of 30-90ug of mouse nerve growth factor, 0.5-1.0 mg of methylcobalamin, 0.1-0.5 mg of adenosylcobalamin, and 2-5 mg of dexamethasone.
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 is composed of mouse nerve growth factor It consists of 30ug, methylcobalamin 0.5mg, adenosylcobalamin 0.5mg, dexamethasone 2mg and lidocaine hydrochloride 1ml, wherein the concentration of lidocaine hydrochloride is selected from any of 0.8%, 1%, 1.5% and 2%. A sort of.
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，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, 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.
本发明的另一目的在于提供一种药物组合物用于制备防治急性期面神经麻痹的药物中的应用，其中，所述用于防治急性期面神经麻痹的药物组合物含有脱水类药物、抗病毒药物、消炎药物、神经修复药物和/或改善血液循环药物的任一种或其组合。Another object of the present invention is to provide a pharmaceutical composition for use in the preparation of drugs for preventing and treating acute facial nerve paralysis, wherein the pharmaceutical composition for preventing and treating acute facial nerve paralysis contains dehydrating drugs and antiviral drugs. , any one or combination of anti-inflammatory drugs, nerve repair drugs and/or blood circulation improving drugs.
本发明的优选技术方案中，所述脱水类药物选自甘露醇、山梨醇、七叶皂苷、七叶皂苷钠、50％的高渗葡萄糖溶液的任一种或其组合。In the preferred technical solution of the present invention, the dehydrating drug is selected from any one of mannitol, sorbitol, aescin, sodium aescin, 50% hypertonic glucose solution or a combination thereof.
本发明的优选技术方案中，所述抗病毒药物选自阿昔洛韦、伐昔洛韦、地巴
唑、犀羚解毒、病毒灵、法匹拉韦(favipiravir)、Paxlovid、莫诺拉韦(Molnupiravir)、奥司他韦、雷米迪维、伦地西韦(Remdesivir，GS-5734)、茚地那韦、沙奎那韦、洛匹那韦、利托那韦(Ritonavir)、阿扎那韦、达芦那韦、替拉那韦、氟沙那韦、恩扎托韦、普瑞托韦、阿巴卡韦、埃替格韦、马立巴韦、雷特格韦、利巴韦林、金刚烷乙胺、奥司他韦、扎那米韦、帕拉米韦、拉尼米韦、更昔洛韦、巴洛沙韦(Baloxavir)、奈非那韦的任一种或其组合。In the preferred technical solution of the present invention, the antiviral drug is selected from the group consisting of acyclovir, valacyclovir, diba Azole, Rhinoceros Jiedu, Virusin, favipiravir, Paxlovid, Molnupiravir, Oseltamivir, Remdesivir, Remdesivir (GS-5734), Indene Dinavir, saquinavir, lopinavir, ritonavir (Ritonavir), atazanavir, darunavir, tipranavir, flusanavir, enzatovir, pritovir Abacavir, elvitegravir, maribavirin, raltegravir, ribavirin, amantadine, oseltamivir, zanamivir, peramivir, lanimivir Any one of ganciclovir, baloxavir, nelfinavir or a combination thereof.
本发明的优选技术方案中，所述消炎药物选自地塞米松、甲基强的松龙、强力松、甲强龙(甲泼尼龙)、可的松、氢化可的松、泼尼松、泼尼松龙的任一种或其组合。In the preferred technical solution of the present invention, the anti-inflammatory drug is selected from dexamethasone, methylprednisolone, prednisolone, methylprednisolone (methylprednisolone), cortisone, hydrocortisone, prednisone, Prednisolone or any combination thereof.
本发明的优选技术方案中，所述神经修复药物和/改善血液循环药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 nerve repair drugs and/or blood circulation improving drugs are selected from the group consisting of mouse nerve growth factor, monosialoganglioside (GM1), cerebrospinalis 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，所述用于防治急性期面神经麻痹的药物组合物含有甘露醇、七叶皂苷钠、阿昔洛韦或伐昔洛韦、地塞米松、强的松、胞磷胆碱钠、银杏叶片、鼠神经生长因子、甲钴胺、腺苷钴胺的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating acute phase facial nerve paralysis contains mannitol, sodium aescinate, acyclovir or valacyclovir, dexamethasone, prednisone, and cytophosphate Any one of sodium choline, ginkgo leaves, mouse nerve growth factor, methylcobalamin, adenosylcobalamin or a combination thereof.
本发明的优选技术方案中，所述用于防治急性期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。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating acute facial nerve paralysis consists of a pharmaceutical composition for oral administration and a pharmaceutical composition for acupoint injection.
本发明的优选技术方案中，单次口服用的药物组合物含有甘露醇125-250ml、甲钴胺0.5mg、消炎药物5mg、法舒地尔30mg、鼠神经生长因子30ug、银杏叶提取物15ml，所述的消炎药物选自地塞米松、七叶皂苷钠、甲强龙的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for single oral administration contains 125-250 ml of mannitol, 0.5 mg of methylcobalamin, 5 mg of anti-inflammatory drugs, 30 mg of fasudil, 30 ug of mouse nerve growth factor, and 15 ml of ginkgo leaf extract. , the anti-inflammatory drug is selected from any one of dexamethasone, sodium aescinate, methylprednisolone 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：In the preferred technical solution of the present invention, the dosage regimen of the oral pharmaceutical composition is:
(1)静脉注射脱水剂甘露醇125-250ml，2次/日；(1) Intravenous injection of the dehydrating agent mannitol 125-250ml, 2 times/day;
(2)肌肉注射1次0.5mg的甲钴胺，每隔1日1次；(2) Inject 0.5 mg of methylcobalamin intramuscularly once every other day;
(3)静脉注射5mg的地塞米松，2次/日；(3) Intravenous injection of 5 mg of dexamethasone, 2 times/day;
(4)静脉注射法舒地尔，30mg/次，2次/日；
(4) Intravenous injection of fasudil, 30 mg/time, 2 times/day;
(5)肌肉注射鼠神经生长因子30ug/次，1次/日；(5) Intramuscular injection of rat nerve growth factor 30ug/time, once/day;
(6)静脉注射银杏叶提取物15ml/次，1次/日。(6) Intravenous injection of Ginkgo leaf extract 15ml/time, once/day.
本发明的优选技术方案中，单次口服用的药物组合物含有甘露醇125-250ml、七叶皂苷钠10-20mg、阿昔洛韦或伐昔洛韦0.3-0.4g、地塞米松或强的松片1-5mg、胞磷胆碱钠片0.2-0.5mg、银杏叶片0.1-0.2g、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 oral administration contains 125-250 ml of mannitol, 10-20 mg of sodium aescin, 0.3-0.4 g of acyclovir or valacyclovir, dexamethasone or prednisone. Disone tablets 1-5mg, Citicoline sodium tablets 0.2-0.5mg, Ginkgo biloba leaves 0.1-0.2g, mouse nerve growth factor 30-90ug, methylcobalamin 0.5-1.0mg, adenosylcobalamin 0.1-0.5mg, Dexamethasone 2-5 mg of any one or 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：In the preferred technical solution of the present invention, the dosage regimen of the oral pharmaceutical composition is:
(1)静脉注射甘露醇(125-250ml/次，1-2次/天)和七叶皂苷钠(20mg/次，1-2次/天)，用药7-14天；(1) Intravenous injection of mannitol (125-250ml/time, 1-2 times/day) and sodium aescinate (20mg/time, 1-2 times/day) for 7-14 days;
(2)静脉注射阿昔洛韦或伐昔洛韦0.3g/次，2次/天，用药7-14天；(2) Intravenous injection of acyclovir or valacyclovir 0.3g/time, 2 times/day, for 7-14 days;
(3)静脉注射地塞米松(5-10mg/天，用药7-10天)；(3) Intravenous injection of dexamethasone (5-10mg/day, 7-10 days of medication);
(4)口服胞磷胆碱钠片(0.2g/次，3次/天，服用2-3周)和银杏叶片(0.1-0.2g/次，3次/天，服用2周)；(4) Oral administration of Citicoline sodium tablets (0.2g/time, 3 times/day, for 2-3 weeks) and Ginkgo biloba leaves (0.1-0.2g/time, 3 times/day, for 2 weeks);
(5)口服醋酸强的松片(5mg/次，2次/天，用药一周)后，口服醋酸强的松片(5mg/次，1次/天，用药一周)；(5) Oral prednisone acetate tablets (5 mg/time, 2 times/day, for one week), followed by oral prednisone acetate tablets (5 mg/time, once/day, for one week);
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由鼠神经生长因子、甲钴胺、维生素B1按照质量比为0.03:0.5:200组成，优选将鼠神经生长因子30ug、甲钴胺0.5mg、维生素B1 200mg配置成5ml药液后,穴位注射。In the preferred technical solution of the present invention, the pharmaceutical composition for a single acupoint injection is composed of mouse nerve growth factor, methylcobalamin, and vitamin B1 in a mass ratio of 0.03:0.5:200. Preferably, 30ug of mouse nerve growth factor, methylcobalamin 0.5 mg of amine and 200 mg of vitamin B1 are mixed into 5 ml of medicinal solution and then injected into the acupoint.
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30ug、甲钴胺0.5mg、维生素B1 200mg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 any one of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 200mg of vitamin B 1 or a combination thereof.
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30-90ug、甲钴胺0.5-1.0mg、腺苷钴胺0.1-0.5mg，地塞米松2-5mg组成。In the preferred technical solution of the present invention, the pharmaceutical composition for a single acupoint injection consists of 30-90ug of mouse nerve growth factor, 0.5-1.0 mg of methylcobalamin, 0.1-0.5 mg of adenosylcobalamin, and 2-5 mg of dexamethasone.
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 a 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. , 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, 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 a single acupoint injection is injected once a day into the acupoint, and the treatment course is 7 days.
本发明的优选技术方案中，每次穴位注射治疗2-6个疗程，优选为4-5个疗程。In the preferred technical solution of the present invention, each acupoint injection treatment lasts for 2-6 courses, preferably 4-5 courses.
本发明的另一目的在于提供一种用于治疗急性期面神经麻痹的治疗方案，所述治疗方案包括使用本发明的用于防治急性期面神经麻痹的药物组合物，所述用于防治急性期面神经麻痹的药物组合物含有脱水类药物、抗病毒药物、消炎药物、神经修复药物和/或改善血液循环药物的任一种或其组合。Another object of the present invention is to provide a treatment plan for treating acute phase facial nerve paralysis. The treatment plan includes using the pharmaceutical composition for preventing and treating acute phase facial nerve paralysis of the present invention. The pharmaceutical composition for paralysis contains any one or a combination of dehydration drugs, antiviral drugs, anti-inflammatory drugs, nerve repair drugs and/or blood circulation improving drugs.
本发明的优选技术方案中，所述脱水类药物选自甘露醇、山梨醇、七叶皂苷、七叶皂苷钠、50％的高渗葡萄糖溶液的任一种或其组合。In the preferred technical solution of the present invention, the dehydrating drug is selected from any one of mannitol, sorbitol, aescin, sodium aescin, 50% hypertonic glucose solution or a combination thereof.
本发明的优选技术方案中，所述抗病毒药物选自阿昔洛韦、伐昔洛韦、地巴唑、犀羚解毒、病毒灵、法匹拉韦(favipiravir)、Paxlovid、莫诺拉韦(Molnupiravir)、奥司他韦、雷米迪维、伦地西韦(Remdesivir，GS-5734)、茚地那韦、沙奎那韦、洛匹那韦、利托那韦(Ritonavir)、阿扎那韦、达芦那韦、替拉那韦、氟沙那韦、恩扎托韦、普瑞托韦、阿巴卡韦、埃替格韦、马立巴韦、
雷特格韦、利巴韦林、金刚烷乙胺、奥司他韦、扎那米韦、帕拉米韦、拉尼米韦、更昔洛韦、巴洛沙韦(Baloxavir)、奈非那韦的任一种或其组合。In the preferred technical solution of the present invention, the antiviral drug is selected from the group consisting of acyclovir, valacyclovir, dibazole, Rhinoceros Jiedu, Virusin, favipiravir, Paxlovid, and monogravir (Molnupiravir), oseltamivir, remdesivir, remdesivir (GS-5734), indinavir, saquinavir, lopinavir, ritonavir (Ritonavir), a Zanavir, darunavir, tipranavir, flusanavir, enzatovir, pretovir, abacavir, elvitegravir, maribabavir, Raltegravir, ribavirin, amantadine, oseltamivir, zanamivir, peramivir, lanamivir, ganciclovir, baloxavir, nefir Any one or combination of navir.
本发明的优选技术方案中，所述消炎药物选自地塞米松、甲基强的松龙、强力松、甲强龙(甲泼尼龙)、可的松、氢化可的松、泼尼松、泼尼松龙的任一种或其组合。In the preferred technical solution of the present invention, the anti-inflammatory drug is selected from dexamethasone, methylprednisolone, prednisolone, methylprednisolone (methylprednisolone), cortisone, hydrocortisone, prednisone, Prednisolone or any combination thereof.
本发明的优选技术方案中，所述神经修复药物和/改善血液循环药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 nerve repair drugs and/or blood circulation improving drugs are selected from the group consisting of mouse nerve growth factor, monosialoganglioside (GM1), cerebrospinalis 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，所述用于防治急性期面神经麻痹的药物组合物含有甘露醇、七叶皂苷钠、阿昔洛韦或伐昔洛韦、地塞米松、强的松、胞磷胆碱钠、银杏叶片、鼠神经生长因子、甲钴胺、腺苷钴胺的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating acute phase facial nerve paralysis contains mannitol, sodium aescinate, acyclovir or valacyclovir, dexamethasone, prednisone, and cytophosphate Any one of sodium choline, ginkgo leaves, mouse nerve growth factor, methylcobalamin, adenosylcobalamin or a combination thereof.
本发明的优选技术方案中，所述用于防治急性期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。In the preferred technical solution of the present invention, the pharmaceutical composition for preventing and treating acute facial nerve paralysis consists of a pharmaceutical composition for oral administration and a pharmaceutical composition for acupoint injection.
本发明的优选技术方案中，单次口服用的药物组合物含有甘露醇125-250ml、甲钴胺0.5mg、消炎药物5mg、法舒地尔30mg、鼠神经生长因子30ug、银杏叶提取物15ml，所述的消炎药物选自地塞米松、七叶皂苷钠、甲强龙的任一种或其组合。In the preferred technical solution of the present invention, the pharmaceutical composition for single oral administration contains 125-250 ml of mannitol, 0.5 mg of methylcobalamin, 5 mg of anti-inflammatory drugs, 30 mg of fasudil, 30 ug of mouse nerve growth factor, and 15 ml of ginkgo leaf extract. , the anti-inflammatory drug is selected from any one of dexamethasone, sodium aescinate, methylprednisolone 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：In the preferred technical solution of the present invention, the dosage regimen of the oral pharmaceutical composition is:
(1)静脉注射脱水剂甘露醇125-250ml，2次/日；(1) Intravenous injection of the dehydrating agent mannitol 125-250ml, 2 times/day;
(2)肌肉注射1次0.5mg的甲钴胺，每隔1日1次；(2) Inject 0.5 mg of methylcobalamin intramuscularly once every other day;
(3)静脉注射5mg的地塞米松，2次/日；(3) Intravenous injection of 5 mg of dexamethasone, 2 times/day;
(4)静脉注射法舒地尔，30mg/次，2次/日；(4) Intravenous injection of fasudil, 30 mg/time, 2 times/day;
(5)肌肉注射鼠神经生长因子30ug/次，1次/日；(5) Intramuscular injection of rat nerve growth factor 30ug/time, once/day;
(6)静脉注射银杏叶提取物15ml/次，1次/日。(6) Intravenous injection of Ginkgo leaf extract 15ml/time, once/day.
本发明的优选技术方案中，单次口服用的药物组合物含有甘露醇125-250ml、七叶皂苷钠10-20mg、阿昔洛韦或伐昔洛韦0.3-0.4g、地塞米松或强的松片1-5mg、
胞磷胆碱钠片0.2-0.5mg、银杏叶片0.1-0.2g、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 oral administration contains 125-250 ml of mannitol, 10-20 mg of sodium aescin, 0.3-0.4 g of acyclovir or valacyclovir, dexamethasone or prednisone. Dipine tablets 1-5mg, Citicoline sodium tablets 0.2-0.5mg, Ginkgo biloba leaves 0.1-0.2g, mouse nerve growth factor 30-90ug, methylcobalamin 0.5-1.0mg, adenosylcobalamin 0.1-0.5mg, dexamethasone 2-5mg any one or 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：In the preferred technical solution of the present invention, the dosage regimen of the oral pharmaceutical composition is:
(1)静脉注射甘露醇(125-250ml/次，1-2次/天)和七叶皂苷钠(20mg/次，1-2次/天)，用药7-14天；(1) Intravenous injection of mannitol (125-250ml/time, 1-2 times/day) and sodium aescinate (20mg/time, 1-2 times/day) for 7-14 days;
(2)静脉注射阿昔洛韦或伐昔洛韦0.3g/次，2次/天，用药7-14天；(2) Intravenous injection of acyclovir or valacyclovir 0.3g/time, 2 times/day, for 7-14 days;
(3)静脉注射地塞米松(5-10mg/天，用药7-10天)；(3) Intravenous injection of dexamethasone (5-10mg/day, 7-10 days of medication);
(4)口服胞磷胆碱钠片(0.2g/次，3次/天，服用2-3周)和银杏叶片(0.1-0.2g/次，3次/天，服用2周)；(4) Oral administration of Citicoline sodium tablets (0.2g/time, 3 times/day, for 2-3 weeks) and Ginkgo biloba leaves (0.1-0.2g/time, 3 times/day, for 2 weeks);
(5)口服醋酸强的松片(5mg/次，2次/天，用药一周)后，口服醋酸强的松片(5mg/次，1次/天，用药一周)；(5) Oral prednisone acetate tablets (5 mg/time, 2 times/day, for one week), followed by oral prednisone acetate tablets (5 mg/time, once/day, for one week);
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由鼠神经生长因子、甲钴胺、维生素B1按照质量比为0.03:0.5:200组成，优选将鼠神经生长因子30ug、甲钴胺0.5mg、维生素B1 200mg配置成5ml药液后,穴位注射。In the preferred technical solution of the present invention, the pharmaceutical composition for a single acupoint injection is composed of mouse nerve growth factor, methylcobalamin, and vitamin B1 in a mass ratio of 0.03:0.5:200. Preferably, 30ug of mouse nerve growth factor, methylcobalamin 0.5 mg of amine and 200 mg of vitamin B1 are mixed into 5 ml of medicinal solution and then injected into the acupoint.
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30ug、甲钴胺0.5mg、维生素B1 200mg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 any one of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 200mg of vitamin B 1 or a combination thereof.
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30-90ug、甲钴胺0.5-1.0mg、腺苷钴胺0.1-0.5mg，地塞米松2-5mg组成。In the preferred technical solution of the present invention, the pharmaceutical composition for a single acupoint injection consists of 30-90ug of mouse nerve growth factor, 0.5-1.0 mg of methylcobalamin, 0.1-0.5 mg of adenosylcobalamin, and 2-5 mg of dexamethasone.
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 a 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，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, 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.
为了清楚地表述本发明，本发明所述的具有修复功效的神经修复细胞蛋白提取物或神经修复细胞蛋白组合物参照专利申请(CN2023100429139、PCT/CN2023/073566、CN2023100429143、PCT/CN2023/073582)制得。In order to clearly describe the present invention, the nerve repair cell protein extract or nerve repair cell protein composition with repair effect described in the present invention is prepared with reference to patent applications (CN2023100429139, PCT/CN2023/073566, CN2023100429143, PCT/CN2023/073582). have to.
本发明的优选技术方案中，所述具有神经修复功效的神经修复细胞蛋白提取物的制备方法，包括如下步骤：In the preferred technical solution of the present invention, the preparation method of the nerve repair cell protein extract with nerve repair effect includes the following steps:
S-1:将密度为5.0×106个/mL-5.0×107个/mL的间充质传代干细胞置于含有DMEM/F12 40-50％、RPMI1640 40-50％、牛血清蛋白(BSA)0.1-2％、表皮细胞生长因子(EGF)1-15ug/mL、成纤维细胞生长因子(FGF)1-15ug/mL、胰岛素转铁蛋白1-15ug/mL、复方氨基酸(18AA)0.01-0.1％和2-10μmol/L应激物的培养基中，再将其置于37.0℃±0.5℃、5％±1.0％CO2条件下培养2h-6h后，分离，洗涤，收集细胞，其中，所述的应激物选自化合物1-16的任一种或其组合；
S-1: Mesenchymal passaged stem cells with a density of 5.0×10 6 /mL-5.0× 10 7 /mL were placed in DMEM/F12 40-50%, RPMI1640 40-50%, bovine serum albumin (BSA) )0.1-2%, epidermal growth factor (EGF) 1-15ug/mL, fibroblast growth factor (FGF) 1-15ug/mL, insulin transferrin 1-15ug/mL, compound amino acid (18AA) 0.01- 0.1% and 2-10 μmol/L stress medium, and then culture it at 37.0℃±0.5℃, 5%±1.0% CO2 for 2h-6h, separate, wash and collect the cells, where , the stressor is selected from any one of compounds 1-16 or a combination thereof;
S-1: Mesenchymal passaged stem cells with a density of 5.0×10 6 /mL-5.0× 10 7 /mL were placed in DMEM/F12 40-50%, RPMI1640 40-50%, bovine serum albumin (BSA) )0.1-2%, epidermal growth factor (EGF) 1-15ug/mL, fibroblast growth factor (FGF) 1-15ug/mL, insulin transferrin 1-15ug/mL, compound amino acid (18AA) 0.01- 0.1% and 2-10 μmol/L stress medium, and then culture it at 37.0℃±0.5℃, 5%±1.0% CO2 for 2h-6h, separate, wash and collect the cells, where , the stressor is selected from any one of compounds 1-16 or a combination thereof;
S-2：将收集细胞按照密度为5.0×106个/mL-5.0×107个/mL分散于溶剂中，再将其置于2℃-8℃条件下超声处理，制得细胞裂解液，其中，所述溶剂选自选自生理盐水、5％葡萄糖溶液、磷酸盐缓冲液(PBS)、TBPS缓冲液、TBST缓冲液、Tris缓冲液的任一种或其组合；S-2: Disperse the collected cells in the solvent at a density of 5.0×10 6 /mL-5.0×10 7 /mL, and then place them at 2℃-8℃ for ultrasonic treatment to prepare a cell lysis solution , wherein the solvent is selected from any one selected from physiological saline, 5% glucose solution, phosphate buffered saline (PBS), TBPS buffer, TBST buffer, Tris buffer or a combination thereof;
S-3:将步骤S-2制得的细胞裂解液分离后，所得的分离液依次经0.45um、0.22um滤膜过滤，即得。S-3: After separating the cell lysate prepared in step S-2, the obtained separation liquid is filtered through 0.45um and 0.22um filters in sequence.
本发明的优选技术方案中，步骤S-1的培养基中含有DMEM/F12 42-45％、RPMI1640 42-45％、牛血清蛋白(BSA)0.5-1.5％、表皮细胞生长因子(EGF)5-10ug/mL、成纤维细胞生长因子(FGF)5-10ug/mL、胰岛素转铁蛋白5-10ug/mL、复方氨基酸(18AA)0.02-0.05％和3-8μmol/L的应激物。In the preferred technical solution of the present invention, the culture medium of step S-1 contains DMEM/F12 42-45%, RPMI1640 42-45%, bovine serum albumin (BSA) 0.5-1.5%, epidermal cell growth factor (EGF) 5 -10ug/mL, fibroblast growth factor (FGF) 5-10ug/mL, insulin transferrin 5-10ug/mL, compound amino acid (18AA) 0.02-0.05% and 3-8μmol/L stressors.
本发明的优选技术方案中，步骤S-1的培养基中含有DMEM/F12 45％、RPMI1640 45％、牛血清蛋白(BSA)0.5％、表皮细胞生长因子(EGF)10ug/mL、成纤维细胞生长因子(FGF)10ug/mL，胰岛素转铁蛋白10ug/mL、复方氨基酸(18AA)0.05％和4-6μmol/L的应激物。In the preferred technical solution of the present invention, the culture medium of step S-1 contains DMEM/F12 45%, RPMI1640 45%, bovine serum albumin (BSA) 0.5%, epidermal growth factor (EGF) 10ug/mL, fibroblasts Growth factor (FGF) 10ug/mL, insulin transferrin 10ug/mL, compound amino acid (18AA) 0.05% and 4-6μmol/L stressors.
本发明的优选技术方案中，步骤S-1的间充质传代干细胞密度为8.0×106-2.0×107个/mL，优选为8.0×106-1.0×107个/mL。In the preferred technical solution of the present invention, the density of mesenchymal passage stem cells in step S-1 is 8.0×10 6 -2.0×10 7 cells/mL, preferably 8.0×10 6 -1.0×10 7 cells/mL.
本发明的优选技术方案中，步骤S-1的间充质传代干细胞在培养基中培养3h-5h，优选为3.5h-4.5h。In the preferred technical solution of the present invention, the mesenchymal passage stem cells in step S-1 are cultured in the culture medium for 3h-5h, preferably 3.5h-4.5h.
本发明的优选技术方案中，步骤S-1中洗涤细胞的溶剂选自生理盐水、5％葡萄糖溶液、磷酸盐缓冲液(PBS)、TBPS缓冲液、TBST缓冲液、Tris缓冲液的任一种或其组合,细胞洗涤次数为2-5次，优选为3-4次。In the preferred technical solution of the present invention, the solvent for washing cells in step S-1 is selected from any one of physiological saline, 5% glucose solution, phosphate buffer (PBS), TBPS buffer, TBST buffer, and Tris buffer. Or a combination thereof, the number of cell washings is 2-5 times, preferably 3-4 times.
本发明的优选技术方案中，步骤S-1所述的分离选自离心、过滤的任一种或其组合，其中，所述离心条件为1000-2000rpm*3-15min，优选为1200rpm-1500rpm*5-10min。
In the preferred technical solution of the present invention, the separation described in step S-1 is selected from any one of centrifugation, filtration or a combination thereof, wherein the centrifugation conditions are 1000-2000rpm*3-15min, preferably 1200rpm-1500rpm* 5-10min.
本发明的优选技术方案中，步骤S-2的超声条件为：在2℃-8℃、25kHZ、360W条件下工作3s再间隙1s，超声处理1-5min。In the preferred technical solution of the present invention, the ultrasonic conditions of step S-2 are: working at 2°C-8°C, 25kHZ, 360W for 3 seconds, followed by a gap of 1 second, and ultrasonic treatment for 1-5 minutes.
本发明的优选技术方案中，步骤S-3所述分离选自2000-8000rpm*10-30min离心、多级离心、多级过滤的任一种或其组合，优选为3000-7000rpm*15-25min。In the preferred technical solution of the present invention, the separation described in step S-3 is selected from any one of 2000-8000rpm*10-30min centrifugation, multi-stage centrifugation, multi-stage filtration or a combination thereof, preferably 3000-7000rpm*15-25min .
本发明的优选技术方案中，步骤S-3的多级离心依次为3000-4000rpm*3-5min、5000-6000rpm*3-5min和7000rpm*5-8min。In the preferred technical solution of the present invention, the multi-stage centrifugation in step S-3 is 3000-4000rpm*3-5min, 5000-6000rpm*3-5min and 7000rpm*5-8min.
本发明的优选技术方案中，所述多级过滤的滤膜孔径选自80um、50um、30um、10um、5um的任一种。In the preferred technical solution of the present invention, the filter membrane pore size of the multi-stage filtration is selected from any one of 80um, 50um, 30um, 10um, and 5um.
本发明的优选技术方案中，将步骤S-3制得的细胞蛋白提取物冻存，优选冻存于-40℃至-20℃。In the preferred technical solution of the present invention, the cell protein extract prepared in step S-3 is frozen and stored, preferably at -40°C to -20°C.
本发明的优选技术方案中，将步骤S-3制得的细胞蛋白提取物采用核酸酶或全能核酸酶的任一种酶解后再分离纯化。In the preferred technical solution of the present invention, the cell protein extract prepared in step S-3 is enzymatically hydrolyzed by either a nuclease or a totipotent nuclease and then separated and purified.
本发明的优选技术方案中，所述间充质传代干细胞的培养或原代间充质干细胞的培养采用本领域的培养方法。In the preferred technical solution of the present invention, the culture of mesenchymal passaged stem cells or the culture of primary mesenchymal stem cells adopts the culture methods in this field.
本发明的优选技术方案中，所述间充质传代干细胞的培养包括下述步骤：将原代间充质干细胞按照初始密度为5.0×105-5.0×106个/ml加入到传代培养基中，再将其置于37.0℃±0.5℃、5％±1.0％CO2条件下培养10-15天，每隔2-3天，观察传代培养基变黄后，半量更换传代培养基，其中，所述传代培养基含有10％FBS、100U/ml青霉素和100ug/ml链霉素的DMEM/F12培养基。In the preferred technical solution of the present invention, the culture of mesenchymal passage stem cells includes the following steps: adding primary mesenchymal stem cells to the passage medium at an initial density of 5.0×10 5 -5.0×10 6 /ml. , and then place it in the culture medium at 37.0℃±0.5℃ and 5%±1.0% CO2 for 10-15 days. Every 2-3 days, after observing that the subculture medium turns yellow, replace half of the subculture medium. , the subculture medium contains DMEM/F12 medium with 10% FBS, 100 U/ml penicillin and 100ug/ml streptomycin.
本发明的优选技术方案中，所述原代间充质干细胞的培养包括下述步骤：In the preferred technical solution of the present invention, the culture of primary mesenchymal stem cells includes the following steps:
1)将脐带清洗消毒后，组织解剖，取华通胶层组织，将其切成3mm3的小块，离心，清洗，收集组织块，将其置于含10％胎牛血清FBS、100ug/ml青霉素、100ug/ml链霉素的DMEM/F12培养基中，再将其置于37.0℃±0.5℃、5％±1.0％CO2条件下培养，每间隔2-3天半量更换培养基，培养至组织块爬出细胞；1) After cleaning and disinfecting the umbilical cord, dissect the tissue, take the Huatong glue layer tissue, cut it into small pieces of 3mm3 , centrifuge, clean, collect the tissue pieces, and place them in a solution containing 10% fetal bovine serum FBS, 100ug/ ml penicillin and 100ug/ml streptomycin in DMEM/F12 culture medium, and then culture it under the conditions of 37.0℃±0.5℃, 5%±1.0% CO2 , and replace the medium with half the medium every 2-3 days. Culture until cells crawl out of the tissue block;
2)振摇，收集低层细胞用PBS清洗后，加入0.25％的胰蛋白酶消化2min-3min，加入等体积的胰蛋白酶终止液停止消化，吸管轻轻吹打，1200-1500rpm/min*5-8min离心后，收集细胞，即得。2) Shake, collect the lower layer cells and wash with PBS, add 0.25% trypsin for digestion for 2min-3min, add an equal volume of trypsin stop solution to stop digestion, gently pipette, and centrifuge at 1200-1500rpm/min*5-8min Afterwards, collect the cells and you are ready.
除非另有说明，本发明涉及液体与液体之间的百分比时，所述的百分比为体积/体积百分比；本发明涉及液体与固体之间的百分比时，所述百分比为体积
/重量百分比；本发明涉及固体与液体之间的百分比时，所述百分比为重量/体积百分比；其余为重量/重量百分比。Unless otherwise stated, when the present invention relates to the percentage between liquids, the percentages are volume/volume percentages; when the present invention relates to the percentages between liquids and solids, the percentages are volume/volume percentages. / weight percentage; when the present invention relates to the percentage between solid and liquid, the percentage is weight/volume percentage; the rest is weight/weight percentage.
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.本发明按照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)规定的穴位以定位和取穴。1. This invention locates and selects acupoints in accordance with the acupoints specified in 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.临床评分采用House-Brakmann面神经功能分级疗效评价表。2. The clinical score uses the House-Brakmann facial nerve function grading efficacy evaluation form.
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、本发明科学组配上市药物用于治疗急性期面瘫，并采用同时给药和/或序贯给药方式治疗患侧，利于减轻早期面瘫水肿，消除面瘫部位炎症，营养面瘫损伤神经并修复损伤髓鞘及轴突。药物组合物中的脱水药物用于消除急性期面瘫水肿，减轻甚至清除急性水肿导致的面神经损伤，利于急性期面瘫的治疗、康复和预后；抗病毒药物用于抗病毒，清除引起面瘫的病因，利于急性期面瘫的治疗、康复和预后；消炎药物用于清除面瘫炎症因子，利于清除面瘫炎症及其水肿，利于急性期面瘫的治疗、康复和预后；神经修复药物和/或改善血液循环的药物用于改善面瘫水肿、病毒、炎症等导致的血液循环障碍，并修复面瘫水肿、病毒、炎症等导致的面神经损伤，利于急性期面瘫的治疗、康复和预后。1. The present invention scientifically combines marketed drugs for the treatment of acute phase facial paralysis, and adopts simultaneous administration and/or sequential administration to treat the affected side, which is beneficial to reducing edema in early stage facial paralysis, eliminating inflammation in the facial paralysis area, nourishing and repairing nerves damaged by facial paralysis. Damage myelin and axons. The dehydration drugs in the pharmaceutical composition are used to eliminate edema of facial paralysis in the acute phase, reduce or even eliminate facial nerve damage caused by acute edema, which is beneficial to the treatment, rehabilitation and prognosis of facial paralysis in the acute phase; the antiviral drugs are used to fight viruses and eliminate the causes of facial paralysis. It is beneficial to the treatment, rehabilitation and prognosis of facial paralysis in the acute phase; anti-inflammatory drugs are used to remove inflammatory factors of facial paralysis, which is beneficial to the removal of inflammation and edema in facial paralysis, and is beneficial to the treatment, rehabilitation and prognosis of facial paralysis in the acute phase; nerve repair drugs and/or drugs to improve blood circulation It is used to improve blood circulation disorders caused by facial paralysis edema, viruses, inflammation, etc., and repair facial nerve damage caused by facial paralysis edema, viruses, inflammation, etc., which is beneficial to the treatment, rehabilitation and prognosis of facial paralysis in the acute phase.
2、本发明采用穴位注射靶向定位给予神经修复药物、改善血液循环药物、神经营养药物、消炎药物、抗病毒药物的任一种或其组合，利用穴位实现精准治疗和科学治疗，提高疗效并减少后遗症发生率，降低用药剂量，降低面部致残率，显著提高治疗效率并降低甚至避免副作用，具有起效快、提高痊愈率、降低复发率、减轻治疗疼痛、缩短治疗周期、无不良反应等优点，减轻患者治疗负担和国家医保负担。2. The present invention uses acupoint injection to deliver any one or a combination of nerve repair drugs, blood circulation improving drugs, neurotrophic drugs, anti-inflammatory drugs, antiviral drugs, using acupoints to achieve precise treatment and scientific treatment, improve curative effect and Reduce the incidence of sequelae, reduce medication dosage, reduce facial disability rate, significantly improve treatment efficiency and reduce or even avoid side effects. It has the characteristics of quick onset, improved recovery rate, reduced recurrence rate, reduced treatment pain, shortened treatment cycle, no adverse reactions, etc. Advantages: Reduce patient treatment burden and national medical insurance burden.
下面结合具体实施例对本发明的详细内容做进一步解释和描述，但并不以此限制本发明的保护范围。The details of the present invention will be further explained and described below in conjunction with specific embodiments, but this does not limit the scope of the present invention.
实施例1具有修复功效的神经修复细胞蛋白提取物的制备 Example 1 Preparation of nerve repair cell protein extract with repair effect
1、原代间充质干细胞的培养
1. Culture of primary mesenchymal stem cells
原代间充质干细胞的培养包括下述步骤：The culture of primary mesenchymal stem cells includes the following steps:
1)将脐带清洗消毒后，组织解剖，取华通胶层组织，将其切成3mm3的小块，离心，清洗，收集组织块，将其置于培养瓶中，加入含10％胎牛血清FBS、100ug/ml青霉素、100ug/ml链霉素的DMEM/F12培养基，再将其置于37℃、5％CO2条件下培养，促进其贴壁，每间隔2-3天,观察培养基变黄后，半量更换培养基，培养10-12天，至组织块边上可见细胞爬出；1) After cleaning and disinfecting the umbilical cord, dissect the tissue, take the Huatong glue layer tissue, cut it into 3mm3 small pieces, centrifuge, clean, collect the tissue pieces, place them in a culture bottle, add 10% fetal bovine DMEM/F12 medium with serum FBS, 100ug/ml penicillin, and 100ug/ml streptomycin, and then culture it at 37°C and 5% CO2 to promote its adhesion. Observe every 2-3 days. After the medium turns yellow, replace half of the medium and culture for 10-12 days until cells can be seen crawling out from the edge of the tissue block;
2)轻轻摇晃，使组织块掉落，分别收集组织块和低层细胞，其中，将收集的组织块再贴壁培养；2) Shake gently to make the tissue blocks fall 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 5 μmol/L compound 16, and then placed at 37°C, 5 After culturing for 4 hours under % CO2 conditions, centrifuge at 1200rpm*5min, wash 3 times with PBS, and collect the cells;
(2)将步骤(1)收集的细胞按照密度为1.0×107个/mL分散于生理盐水中，在2-8℃、25kHz、360W条件下超声3s、间隙1s，超声2min，制得细胞裂解液；
(2) Disperse the cells collected in step (1) in physiological saline at a density of 1.0 × 10 7 cells/mL, ultrasonicate for 3s, 1s gap, and 2min under the conditions of 2-8°C, 25kHz, 360W to obtain cells. Lysis solution;
(3)将步骤(2)制得的细胞裂解液置于7000rpm*20min离心，将所得的离心液依次经0.45um、0.22um滤膜过滤，即得细胞蛋白提取物；(3) Centrifuge the cell lysate prepared in step (2) at 7000rpm*20min, and filter the obtained centrifuge through 0.45um and 0.22um filters in sequence to obtain the cell protein extract;
(4)在步骤(3)制得的细胞蛋白提取物加入所需量的甘露醇，搅拌，混合均匀后，冻干，所得冻干制剂中含有5％的甘露醇(m/m)。(4) Add the required amount of mannitol to the cell protein extract prepared in step (3), stir, mix evenly, and freeze-dry. The resulting freeze-dried preparation contains 5% mannitol (m/m).
试验例1本发明药物组合物用于急性期面瘫的治疗效果研究 Test Example 1 Study on the therapeutic effect of the pharmaceutical composition of the present invention for acute facial paralysis
选取急性期患者60名，分为1组(10名)、2组(40名)、3组(10名)。患者入组标准：符合面神经炎中医、西医诊断标准，患者均为单侧急性发病，出现明显症状于数小时或1-3天；20-70岁；发病15天以内；H-B分级在II级以上；知情同意接受本试验；依从性好、非昏迷患者及第一次发病或既往有面瘫病史，但无后遗症。禁忌症：面神经完全断裂或缺失者；注射部位感染或皮肤损伤者；孕妇或哺乳期妇女者，可能影响胎儿或婴儿的健康；对药物过敏者，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 in the acute phase were selected and divided into group 1 (10 patients), group 2 (40 patients), and group 3 (10 patients). Patient inclusion criteria: Meet the diagnostic criteria of facial neuritis in traditional Chinese medicine and Western medicine. Patients are all unilateral acute onset, with obvious symptoms appearing within a few hours or 1-3 days; 20-70 years old; onset within 15 days; H-B grade above level II ; Informed consent to accept this trial; patients with good compliance, non-coma, first onset of illness or previous history of facial paralysis, but no sequelae. Contraindications: Those with complete rupture or loss of the facial nerve; those with infection or skin damage at the injection site; those who are pregnant or breastfeeding, as it may affect the health of the fetus or baby; those who are allergic to drugs, which may cause allergic reactions or other adverse reactions; those with mental disorders or Those who are unable to cooperate with rehabilitation or corrective training.
1组的治疗方案(每个疗程7天，治疗4个疗程)包括口服给药和穴位注射给药。The treatment plan of Group 1 (7 days each, 4 courses of treatment) included oral administration and acupoint injection.
1、术后口服药物的同时给药和/或序贯给药的方案：1. Simultaneous administration and/or sequential administration of oral drugs after surgery:
1)静脉注射脱水剂甘露醇125-250ml，2次/日；1) Intravenous injection of 125-250ml of mannitol, a dehydrating agent, 2 times a day;
2)肌肉注射1次0.5mg的甲钴胺，每隔1日1次；2) Inject 0.5 mg of methylcobalamin intramuscularly once every other day;
3)静脉注射5mg的地塞米松，2次/日；3) Intravenous injection of 5 mg of dexamethasone, twice a day;
4)静脉注射法舒地尔，30mg/次，2次/日；4) Intravenous injection of Fasudil, 30 mg/time, 2 times/day;
5)肌肉注射鼠神经生长因子30ug/次，1次/日；5) Intramuscular injection of rat nerve growth factor 30ug/time, once/day;
6)静脉注射银杏叶提取物15ml/次，1次/日；6) Intravenous injection of Ginkgo leaf extract 15ml/time, once/day;
2、穴位注射给药方案：2. Acupoint injection administration plan:
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，配置成5ml药液,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 is composed of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, and 200mg of vitamin B1. It is formulated into 5ml of medicinal solution for immediate use. Select the Yangbai point, temple, and four white points on the affected side of the face. Acupoint injections are performed at the acupoint, Yingxiang acupoint, Juliao acupoint, Dicang acupoint and Jieche acupoint, once a day.
2组的治疗方案(每个疗程7天，治疗4个疗程)包括口服给药和穴位注射给药。The treatment plan for the 2 groups (7 days each, 4 courses of treatment) included oral administration and acupoint injection.
1、口服药物的同时给药和/或序贯给药的方案：
1. Simultaneous administration and/or sequential administration of oral drugs:
(1)静脉注射甘露醇(125ml/次，2次/天)和七叶皂苷钠(20mg/次，2次/天)，用药14天；(1) Intravenous injection of mannitol (125ml/time, 2 times/day) and sodium aescinate (20mg/time, 2 times/day) for 14 days;
(2)静脉注射伐昔洛韦0.3g/次，2次/天，用药14天；(2) Intravenous injection of valacyclovir 0.3g/time, 2 times/day, for 14 days;
(3)静脉注射地塞米松10mg/天，用药10天；(3) Intravenous injection of dexamethasone 10 mg/day for 10 days;
(4)口服胞磷胆碱钠片(0.2g/次，3次/天，服用2-3周)和银杏叶片(0.1g/次，3次/天，服用2周)；(4) Oral administration of Citicoline sodium tablets (0.2g/time, 3 times/day, for 2-3 weeks) and Ginkgo biloba leaves (0.1g/time, 3 times/day, for 2 weeks);
(5)口服醋酸强的松片(5mg/次，2次/天，用药一周)后，口服醋酸强的松片(5mg/次，1次/天，用药一周)；(5) Oral prednisone acetate tablets (5 mg/time, 2 times/day, for one week), followed by oral prednisone acetate tablets (5 mg/time, once/day, for one week);
2、穴位注射给药方案：2. Acupoint injection administration plan:
单次穴位注射的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg、地塞米松5mg和盐酸利多卡因1ml组成,临配临用，选取患侧面部的阳白穴、太阳穴、四白穴、迎香穴、巨髎穴、地仓穴和颊车穴进行穴位注射，每天穴位注射1次。The pharmaceutical composition for a single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride. Acupoint injection is performed at Yangbai point, Taiyang point, Sibai point, Yingxiang point, Juliiao point, Dicang point and Jieche point, once a day.
3组的治疗方案(每个疗程7天，治疗4个疗程)包括口服给药和穴位注射给药。The treatment plan for the 3 groups (7 days each, 4 courses of treatment) included oral administration and acupoint injection.
1、口服药物的同时给药和/或序贯给药的方案：1. Simultaneous administration and/or sequential administration of oral drugs:
(1)静脉注射甘露醇(125ml/次，2次/天)和七叶皂苷钠(20mg/次，2次/天)，用药14天；(1) Intravenous injection of mannitol (125ml/time, 2 times/day) and sodium aescinate (20mg/time, 2 times/day) for 14 days;
(2)静脉注射伐昔洛韦0.3g/次，2次/天，用药14天；(2) Intravenous injection of valacyclovir 0.3g/time, 2 times/day, for 14 days;
(3)静脉注射地塞米松10mg/天，用药10天；(3) Intravenous injection of dexamethasone 10 mg/day for 10 days;
(4)口服胞磷胆碱钠片(0.2g/次，3次/天，服用2-3周)和银杏叶片(0.1g/次，3次/天，服用2周)；(4) Oral administration of Citicoline sodium tablets (0.2g/time, 3 times/day, for 2-3 weeks) and Ginkgo biloba leaves (0.1g/time, 3 times/day, for 2 weeks);
(5)口服醋酸强的松片(5mg/次，2次/天，用药一周)后，口服醋酸强的松片(5mg/次，1次/天，用药一周)；(5) Oral prednisone acetate tablets (5 mg/time, 2 times/day, for one week), followed by oral prednisone acetate tablets (5 mg/time, once/day, for one week);
2、穴位注射给药方案：2. Acupoint injection administration plan:
(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.
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：治疗当天起效，且有超过70％的患者的耳朵疼痛明显缓解，超过40％的患者面部肌肉改善，歪嘴、面部不僵化。治疗7天的有效率70％和显效率40％。治疗15天的有效率80％，显效70％。治疗30天的痊愈率超过80％。Group 1: It takes effect on the same day of treatment, and more than 70% of patients have significant relief of ear pain, more than 40% of patients have improved facial muscles, and their mouths are not crooked and their faces are not rigid. The effective rate after 7 days of treatment is 70% and the effective rate is 40%. The effective rate of treatment for 15 days is 80%, and the effective rate is 70%. The recovery rate within 30 days of treatment exceeds 80%.
2组：治疗当天即起效，且有超过80％的患者的耳朵疼痛明显缓解，超过50％的患者面部肌肉改善，歪嘴、面部不僵化。治疗7天的有效率80％和显效率50％。治疗15天的有效率90％，显效80％。治疗30天的痊愈率超过90％，且基本无后遗症，满意度为100分。未痊愈患者根据患者的病情及用药史，继续用药1-3个疗程，基本痊愈。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: It takes effect on the same day of treatment, and more than 80% of patients have significant relief of ear pain, and more than 50% of patients have improved facial muscles, with their mouths crooked and their faces no longer rigid. The effective rate after 7 days of treatment is 80% and the effective rate is 50%. The effective rate of treatment for 15 days is 90%, and the effect is 80%. The recovery rate after 30 days of treatment is over 90%, with basically no sequelae, and the satisfaction score is 100 points. Patients who have not recovered can basically recover after continuing to take medication for 1-3 courses based on the patient's condition and medication history. 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.
试验组3：起效更快，面部肌肉僵化改善作用更明显。患者治疗当天即起效，且有超过90％的患者的耳朵疼痛明显缓解，超过60％的患者面部肌肉改善，歪嘴、面部不僵化。治疗7天的有效率90％和显效率70％。治疗15天的显效90％。治疗30天的痊愈率100％，且基本无后遗症，满意度为100分。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。Test Group 3: The effect is faster and the improvement effect on facial muscle stiffness is more obvious. It takes effect on the same day of treatment, and more than 90% of patients have significant relief of ear pain, and more than 60% of patients have improved facial muscles, with their mouths crooked and their faces no longer rigid. The effective rate after 7 days of treatment is 90% and the effective rate is 70%. 90% effective after 15 days of treatment. The recovery rate within 30 days of treatment was 100%, with basically no sequelae, and the satisfaction score was 100 points. 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 shall all belong to the right of the present invention. the scope of protection claimed.
Claims (10)
- 一种用于防治急性期面神经麻痹的药物组合物，所述组合物含有脱水类药物、抗病毒药物、消炎药物、神经修复药物和/或改善血液循环药物的任一种或其组合。A pharmaceutical composition for preventing and treating facial nerve paralysis in the acute phase. The composition contains any one or a combination of dehydration drugs, antiviral drugs, anti-inflammatory drugs, nerve repair drugs and/or blood circulation improving drugs.
- 如权利要求1所述的药物组合物，所述用于防治急性期面神经麻痹的药物组合物含有甘露醇、七叶皂苷钠、阿昔洛韦或伐昔洛韦、地塞米松、强的松、胞磷胆碱钠、银杏叶片、鼠神经生长因子、甲钴胺、腺苷钴胺的任一种或其组合。The pharmaceutical composition according to claim 1, which is used to prevent and treat facial nerve paralysis in the acute phase and contains mannitol, sodium aescin, acyclovir or valacyclovir, dexamethasone, and prednisone. , Citicoline sodium, Ginkgo biloba leaves, mouse nerve growth factor, methylcobalamin, adenosylcobalamin any one or a combination thereof.
- 如权利要求1-2任一项所述的药物组合物，所述用于防治急性期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 pharmaceutical composition according to any one of claims 1-2, wherein the pharmaceutical composition for preventing and treating acute phase 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任一项所述的药物组合物，，单次口服用的药物组合物含有甘露醇125-250ml、七叶皂苷钠10-20mg、阿昔洛韦或伐昔洛韦0.3-0.4g、地塞米松或强的松片1-5mg、胞磷胆碱钠片0.2-0.5mg、银杏叶片0.1-0.2g、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 pharmaceutical composition according to any one of claims 1 to 3, the pharmaceutical composition for single oral administration contains 125-250 ml of mannitol, 10-20 mg of sodium aescin, and 0.3 acyclovir or valacyclovir. -0.4g, dexamethasone or prednisone tablets 1-5mg, citicoline sodium tablets 0.2-0.5mg, ginkgo leaves 0.1-0.2g, mouse nerve growth factor 30-90ug, methylcobalamin 0.5-1.0mg, Adenosylcobalamin 0.1-0.5mg, dexamethasone 2-5mg any one or a combination thereof.
- 如权利要求1-4任一项所述的药物组合物，口服用药物组合物的给药方案为：The pharmaceutical composition according to any one of claims 1 to 4, the dosage regimen of the oral pharmaceutical composition is:(1)静脉注射甘露醇(125-250ml/次，1-2次/天)和七叶皂苷钠(20mg/次，1-2次/天)，用药7-14天；(1) Intravenous injection of mannitol (125-250ml/time, 1-2 times/day) and sodium aescinate (20mg/time, 1-2 times/day) for 7-14 days;(2)静脉注射阿昔洛韦或伐昔洛韦0.3g/次，2次/天，用药7-14天；(2) Intravenous injection of acyclovir or valacyclovir 0.3g/time, 2 times/day, for 7-14 days;(3)静脉注射地塞米松(5-10mg/天，用药7-10天)；(3) Intravenous injection of dexamethasone (5-10mg/day, 7-10 days of medication);(4)口服胞磷胆碱钠片(0.2g/次，3次/天，服用2-3周)和银杏叶片(0.1-0.2g/次，3次/天，服用2周)；(4) Oral administration of Citicoline sodium tablets (0.2g/time, 3 times/day, for 2-3 weeks) and Ginkgo biloba leaves (0.1-0.2g/time, 3 times/day, for 2 weeks);(5)口服醋酸强的松片(5mg/次，2次/天，用药一周)后，口服醋酸强的松片(5mg/次，1次/天，用药一周)；(5) Oral prednisone acetate tablets (5 mg/time, 2 times/day, for one week), followed by oral prednisone acetate tablets (5 mg/time, once/day, for one week);
- 如权利要求1-5任一项所述的药物组合物，单次穴位注射的药物组合物由鼠神经生长因子30-90ug、甲钴胺0.5-1.0mg、腺苷钴胺0.1-0.5mg，地塞米松2-5mg组成。The pharmaceutical composition according to any one of claims 1 to 5, the pharmaceutical composition for a single acupoint injection consists of mouse nerve growth factor 30-90ug, methylcobalamin 0.5-1.0mg, adenosylcobalamin 0.1-0.5mg, Composition of dexamethasone 2-5mg.
- 如权利要求1-6任一项所述的药物组合物，所述单次穴位注射用的药物组合物任选地含有100-300mg具有修复功效的神经修复细胞蛋白提取物和/或神经 修复蛋白组合物的任一种或其组合。The pharmaceutical composition according to any one of claims 1 to 6, the pharmaceutical composition for single point injection optionally contains 100-300 mg of nerve repair cell protein extract with repair effect and/or nerve Any one or combination of repair protein compositions.
- 如权利要求1-7任一项所述的药物组合物，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。The pharmaceutical composition according to any one of claims 1 to 7 is selected from the Yangbai point, temple point, Sibai point, Yingxiang point, Juliiao point, Dicang point and Jieche point on the affected side of the face for acupoint injection.
- 如权利要求1-8任一项所述的药物组合物用于制备防治急性期面神经麻痹的药物中的应用，其中，所述用于防治急性期面神经麻痹的药物组合物含有脱水类药物、抗病毒药物、消炎药物、神经修复药物和/或改善血液循环药物的任一种或其组合。The pharmaceutical composition according to any one of claims 1 to 8 is used to prepare a medicine for preventing and treating acute facial nerve paralysis, wherein the pharmaceutical composition for preventing and treating acute facial nerve paralysis contains dehydration drugs, anti-inflammatory drugs and Any one or combination of viral drugs, anti-inflammatory drugs, neurorepair drugs and/or blood circulation improving drugs.
- 一种用于治疗急性期面神经麻痹的治疗方案，所述治疗方案包括如权利要求1-8任一项所述的药物组合物用于防治急性期面神经麻痹的药物组合物，所述用于防治急性期面神经麻痹的药物组合物含有脱水类药物、抗病毒药物、消炎药物、神经修复药物和/或改善血液循环药物的任一种或其组合。 A treatment plan for treating acute phase facial nerve paralysis, the treatment plan comprising a pharmaceutical composition as claimed in any one of claims 1 to 8. A pharmaceutical composition for preventing and treating acute phase facial nerve paralysis, which is used to prevent and treat acute phase facial nerve paralysis. The pharmaceutical composition for facial nerve paralysis in the acute phase contains any one or a combination of dehydration drugs, antiviral drugs, anti-inflammatory drugs, nerve repair drugs and/or blood circulation improving drugs.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211101347 | 2022-09-09 | ||
| CN202211101693.4 | 2022-09-09 | ||
| CN202211101693 | 2022-09-09 | ||
| CN202211101347.6 | 2022-09-09 |
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| WO2024051844A1 true WO2024051844A1 (en) | 2024-03-14 |
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ID=90127306
Family Applications (6)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| 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/CN2023/117896 WO2024051844A1 (en) | 2022-09-09 | 2023-09-09 | Pharmaceutical composition for preventing and treating acute stage facial nerve paralysis 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/CN2023/117899 WO2024051847A1 (en) | 2022-09-09 | 2023-09-09 | Pharmaceutical composition for preventing and treating facial nerve micro-entrapment syndrome and use thereof |
| PCT/CN2023/117894 WO2024051843A1 (en) | 2022-09-09 | 2023-09-09 | Pharmaceutical composition for preventing and treating convalescent stage facial nerve paralysis and use thereof |
Family Applications Before (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| 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 |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| 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/CN2023/117899 WO2024051847A1 (en) | 2022-09-09 | 2023-09-09 | Pharmaceutical composition for preventing and treating facial nerve micro-entrapment syndrome and use thereof |
| PCT/CN2023/117894 WO2024051843A1 (en) | 2022-09-09 | 2023-09-09 | Pharmaceutical composition for preventing and treating convalescent stage facial nerve paralysis and use thereof |
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| CN (6) | CN117679519A (en) |
| WO (6) | WO2024051846A1 (en) |
Citations (2)
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| CN102988403A (en) * | 2012-12-06 | 2013-03-27 | 祁建春 | Injection medicine composition used for treating facial paralysis in acute stage |
| CN113082043A (en) * | 2021-04-20 | 2021-07-09 | 王化兰 | Medicine for treating facial paralysis by traditional Chinese medicine acupoint injection |
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-
2023
- 2023-09-09 WO PCT/CN2023/117898 patent/WO2024051846A1/en unknown
- 2023-09-09 WO PCT/CN2023/117900 patent/WO2024051848A1/en unknown
- 2023-09-09 WO PCT/CN2023/117896 patent/WO2024051844A1/en unknown
- 2023-09-09 WO PCT/CN2023/117897 patent/WO2024051845A1/en unknown
- 2023-09-09 CN CN202311159238.4A patent/CN117679519A/en active Pending
- 2023-09-09 WO PCT/CN2023/117899 patent/WO2024051847A1/en unknown
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- 2023-09-09 CN CN202311159241.6A patent/CN117679520A/en active Pending
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Also Published As
| Publication number | Publication date |
|---|---|
| CN117679649A (en) | 2024-03-12 |
| CN117679520A (en) | 2024-03-12 |
| WO2024051847A1 (en) | 2024-03-14 |
| WO2024051846A1 (en) | 2024-03-14 |
| WO2024051848A1 (en) | 2024-03-14 |
| WO2024051845A1 (en) | 2024-03-14 |
| CN117679518A (en) | 2024-03-12 |
| WO2024051843A1 (en) | 2024-03-14 |
| CN117679521A (en) | 2024-03-12 |
| CN117679522A (en) | 2024-03-12 |
| CN117679519A (en) | 2024-03-12 |
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