Pharmaceutical composition for preventing and treating recovery stage facial nerve palsy and application thereof

Abstract

The present application relates to a kind of drug composition for preventing and treating recovery stage facial nerve palsy and its application, the composition contains any one or its combination of dehydrating drug, antiviral drug, anti-inflammatory drug, nerve repair drug and / or blood circulation improving drug, traditional Chinese medicine preparation.The drug composition of the present application is combined with radio frequency operation and nerve repair drug and rehabilitation exercise, beneficial to promote trophic nerve, promote myelin and axon repair, with synergistic effect, fast effect, high efficiency, high cure rate, basically no side effect and basically no recurrence rate and the like, significantly improve the treatment prognosis and quality of life of patient.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically relating to a pharmaceutical composition for the prevention and treatment of facial nerve palsy in the recovery period and its application. Background Technology

[0002] Facial nerve palsy (also known as facial paralysis) is a common facial nerve disorder (accounting for 60%-75% of cases), with an incidence rate of 11.5-53.3 per 100,000 people and a recurrence rate of 2.6%-15.2%. Patients are predominantly men aged 20-40. Its main clinical manifestations include reduced or lost facial voluntary movement and expression function, malnutrition of the facial nerve and facial muscles, etc., affecting the patient's appearance, personal dignity, and social image. In severe cases, it can even lead to psychological disorders such as depression and anxiety. Clinically, facial nerve palsy is divided into the acute phase (within 15 days of onset), the recovery phase (16 days to 6 months of onset), and the sequelae phase (more than 6 months of onset) based on the duration of the illness.

[0003] The etiology of facial nerve palsy remains unclear. Viral infections (such as latent herpes simplex virus type I and herpes zoster virus infections) and reactivation following viral infection are widely accepted as contributing factors. Familial facial nerve palsy may be secondary to hereditary autoimmune diseases involving human leukocyte antigens. Abnormalities in the facial canal anatomy, stenosis of the facial canal, and drastic changes in climate and temperature can all be risk factors for facial nerve palsy. Different locations of damage to the facial nerve (including preganglionic geniculate lesions, geniculate ganglion lesions, and lesions near the stylomastoid foramen) result in different clinical symptoms. If facial nerve palsy is not treated promptly or recovery is incomplete, it is often accompanied by atrophy of the paralyzed muscles, blepharospasm, synkinesis, and a pulling sensation on the affected side of the face. Furthermore, regenerated nerve fibers may grow into adjacent nerve fiber pathways, controlling symptoms originally caused by other nerve fiber effectors. Currently, there are no effective drugs or treatment plans for the recovery phase of facial nerve palsy.

[0004] 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 serve as essential technical references and components of this application. Summary of the Invention

[0005] The purpose of this invention is to provide a pharmaceutical composition for use in the preparation of a drug for preventing and treating facial nerve palsy in the recovery period, wherein the pharmaceutical composition for preventing and treating facial nerve palsy in the recovery period contains any one or a combination of dehydrating drugs, antiviral drugs, anti-inflammatory drugs, nerve repair drugs and / or drugs that improve blood circulation, and traditional Chinese medicine preparations.

[0006] In a preferred embodiment of the present invention, the dehydrating agent is selected from any one or a combination of mannitol, sorbitol, aescin, sodium aescinate, and 50% hypertonic glucose solution.

[0007] In a preferred embodiment of the present invention, the antiviral drug is selected from any one or a combination of acyclovir, valacyclovir, dibazol, tadalafil, ribavirin, favipiravir, Paxlovid, molnupiravir, oseltamivir, remdesivir (GS-5734), indinavir, saquinavir, lopinavir, ritonavir, atazanavir, darunavir, telanavir, flushanavir, enzatovir, pretovir, abacavir, erticavir, maribavir, retegvir, ribavirin, amantadine ethylamine, oseltamivir, zanamivir, peramivir, lanimivir, ganciclovir, baloxavir, and nelfinavir.

[0008] In a preferred embodiment of the present invention, the anti-inflammatory drug is selected from any one or a combination of dexamethasone, methylprednisolone, prednisolone, methylprednisolone, cortisone, hydrocortisone, prednisolone, and prednisolone.

[0009] In a preferred embodiment of the present invention, the nerve repair drug and / or blood circulation improving drug is selected from any one or a combination of mouse nerve growth factor, monosialotetrahexosylganglioside (GM1), cerebrolysin, methylcobalamin, adenosylcobalamin, compound vitamin B, butylphthalide, cinnarizine maleate, edaravone, edaravone dexborneol, citicoline, citicoline sodium, ganglioside, piracetam, piracetam, piracetam, nerve growth factor, citicoline, neurotoxin, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin E, compound brain peptide ganglioside, brain protein, and nervonic acid.

[0010] In the preferred embodiment of the present invention, the traditional Chinese medicine preparation is selected from any one or a combination of the following: Facial Paralysis Pills, Ginseng Rejuvenating Pills, Ginkgo Leaf Tablets or Ginkgo Leaf Extract, Ge Gen Tang combined with Qian Zheng San or its modified formula, Da Qin Jiao Tang or its modified formula, Long Dan Xie Gan Tang combined with Gua Lou Hong Hua Tang or its modified formula, Di Tan Tang combined with Qian Zheng San or its modified formula, Bu Yang Huan Wu Tang combined with Qian Zheng San or its modified formula, Shang Shi Zhi Tong Gao, She Xiang Hu Gu Gao, or a traditional Chinese medicine ointment made from fresh ginger, ginseng, lotus root, yam, licorice, chicory, rose, and angelica.

[0011] In a preferred embodiment of the present invention, the pharmaceutical composition for preventing and treating facial nerve palsy in the recovery period contains any one or a combination of mannitol, sodium aescinate, acyclovir, valacyclovir, dibazol, dexamethasone, prednisone, cytidine diphosphate choline sodium, ginkgo biloba tablets, mouse nerve growth factor, methylcobalamin, and adenosylcobalamin.

[0012] In a preferred embodiment of the present invention, the pharmaceutical composition for preventing and treating facial nerve palsy in the recovery period contains any one or a combination of mannitol, sodium aescinate, acyclovir, valacyclovir, dibazol, dexamethasone, prednisone, cytidine diphosphate choline sodium, ginkgo biloba tablets, mouse nerve growth factor, methylcobalamin, and adenosylcobalamin.

[0013] In a preferred embodiment of the present invention, the pharmaceutical composition for preventing and treating facial nerve palsy in the recovery period consists of a single oral pharmaceutical composition and a single acupoint injection pharmaceutical composition.

[0014] In a preferred embodiment of the present invention, the pharmaceutical composition for single oral administration contains 20-40 mg of sodium aescinate, 10-30 mg of dibazol, 0.5-1.5 mg of methylcobalamin, 0.5-1.5 mg of adenosylcobalamin, 0.2-0.6 g of ginkgo biloba tablets, and 3-6 g of ginseng regeneration pills.

[0015] In a preferred embodiment of the present invention, the administration regimen of the oral pharmaceutical composition is as follows:

[0016] (1) Orally administer sodium aescinate 20mg / time, twice a day, for 1 month;

[0017] (2) Oral administration of dibazol 10mg / time, 3 times / day, for 1 month;

[0018] (3) Oral administration of mecobalamin 0.5 mg / time and adenosylcobalamin 0.5 mg / time, 3 times / day, for 1 month;

[0019] (4) Take 0.2g of Ginkgo biloba tablets orally three times a day for one month;

[0020] (5) Take 3g of Renshen Zaizao Pills orally twice a day for one month.

[0021] In a preferred embodiment of the present invention, the oral pharmaceutical composition is selected from any one or a combination thereof of simultaneous administration or sequential administration.

[0022] In a preferred embodiment of the present invention, the pharmaceutical composition for single acupoint injection contains any one or a combination of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, and 200mg of vitamin B1.

[0023] In a preferred embodiment of the present invention, the drug composition for single acupoint injection consists of 30-90ug of mouse nerve growth factor, 0.5-1.0mg of methylcobalamin, 0.5-1.0mg of adenosylcobalamin, 2-5mg 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%.

[0024] In a preferred embodiment of the present invention, the drug composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 2mg of dexamethasone, and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.

[0025] In a preferred embodiment of the present invention, the drug composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 1.0mg of adenosylcobalamin, 5mg of dexamethasone, and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.

[0026] In a preferred embodiment of the present invention, the drug composition for single acupoint injection consists of 90ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone, and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.

[0027] In a preferred embodiment of the present invention, the drug composition for single acupoint injection consists of 60ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 3mg of dexamethasone, and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.

[0028] In a preferred embodiment of the present invention, the pharmaceutical composition for single acupoint injection optionally contains 100-300 mg of any one or a combination of nerve repair cell protein extracts and / or nerve repair protein compositions with repairing effects.

[0029] In a preferred embodiment of the present invention, the drug composition for single acupoint injection is prepared and used immediately.

[0030] In a preferred embodiment of the present invention, acupoints such as Yangbai, Taiyang, Sibai, Yingxiang, Juliao, Dicang, and Jiache on the affected side of the face are selected for acupoint injection.

[0031] In a preferred embodiment of the present invention, the drug composition for single acupoint injection is injected into the acupoint once a day for 7 days as a course of treatment.

[0032] In the preferred embodiment of the present invention, each acupoint injection treatment is performed for 2-6 courses of treatment, preferably 4-5 courses of treatment.

[0033] In a preferred embodiment of the present invention, the pharmaceutical composition for preventing and treating facial nerve palsy during the recovery period may optionally be used in combination with radiofrequency surgery, rehabilitation exercises, or a combination thereof.

[0034] In a preferred embodiment of the present invention, the radiofrequency surgery is performed at 41℃-42℃, 90V-140V, and 2Hz-6Hz, based on a long-duration temperature-controlled high-voltage variable frequency pulse radiofrequency for 800-1400 seconds.

[0035] In a preferred embodiment of the present invention, the radiofrequency surgery is performed at 41℃-42℃, 100V-120V, and 3Hz-5Hz, based on a long-duration temperature-controlled high-voltage variable frequency pulse radiofrequency for 960-1200 seconds.

[0036] In a preferred embodiment of the present invention, the rehabilitation training exercise is a facial paralysis rehabilitation training exercise created by the inventor (copyright registration number: Guo Zuo Deng Zi-2022-I-10250228 and copyright registration number: Guo Zuo Deng Zi-2022-F-10250229).

[0037] In a preferred embodiment of the present invention, the rehabilitation exercise training is selected from any one or a combination of the first set of rehabilitation exercise training and the second set of rehabilitation exercise training.

[0038] In the preferred embodiment of the present invention, the first set of rehabilitation exercises includes: first, looking in a mirror; second, slowly closing the eyes, closing the eyes for 5 seconds, then opening the eyes and holding for 5 seconds, while controlling the mouth corners to not lift, correcting the associated movements; training the first set of rehabilitation exercises three times a day, with each set being 30 repetitions.

[0039] In the preferred embodiment of the present invention, the second set of rehabilitation exercises includes: first, looking in a mirror; second, opening the eyes and trying to keep the nerve branches silent; and third, pursing the lips, baring the teeth, and puffing out the cheeks around the mouth; and training the first set of rehabilitation exercises three times a day, with each set being trained 10 times.

[0040] In a preferred embodiment of the present invention, the treatment plan for preventing and treating facial nerve palsy during the recovery period includes pulsed radiofrequency surgery, postoperative oral medication and acupoint injection, as well as intraoperative and postoperative rehabilitation exercises.

[0041] In a preferred embodiment of the present invention, the facial nerve palsy is selected from any one or a combination of hemifacial spasm, facial paralysis / related movement, trigeminal neuralgia, glossopharyngeal neuralgia, facial neuritis, peripheral facial paralysis, and oculomotor spasm repair.

[0042] The purpose of this invention is to provide a pharmaceutical composition for preventing and treating facial nerve palsy in the recovery period. The pharmaceutical composition contains any one or a combination of dehydrating drugs, antiviral drugs, anti-inflammatory drugs, nerve repair drugs and / or drugs that improve blood circulation, and traditional Chinese medicine preparations.

[0043] In a preferred embodiment of the present invention, the dehydrating agent is selected from any one or a combination of mannitol, sorbitol, aescin, sodium aescinate, and 50% hypertonic glucose solution.

[0044] In a preferred embodiment of the present invention, the antiviral drug is selected from any one or a combination of acyclovir, valacyclovir, dibazol, tadalafil, ribavirin, favipiravir, Paxlovid, molnupiravir, oseltamivir, remdesivir (GS-5734), indinavir, saquinavir, lopinavir, ritonavir, atazanavir, darunavir, telanavir, flushanavir, enzatovir, pretovir, abacavir, erticavir, maribavir, retegvir, ribavirin, amantadine ethylamine, oseltamivir, zanamivir, peramivir, lanimivir, ganciclovir, baloxavir, and nelfinavir.

[0045] In a preferred embodiment of the present invention, the anti-inflammatory drug is selected from any one or a combination of dexamethasone, methylprednisolone, prednisolone, methylprednisolone, cortisone, hydrocortisone, prednisolone, and prednisolone.

[0046] In a preferred embodiment of the present invention, the nerve repair drug and / or blood circulation improving drug is selected from any one or a combination of mouse nerve growth factor, monosialotetrahexosylganglioside (GM1), cerebrolysin, methylcobalamin, adenosylcobalamin, compound vitamin B, butylphthalide, cinnarizine maleate, edaravone, edaravone dexborneol, citicoline, citicoline sodium, ganglioside, piracetam, piracetam, piracetam, nerve growth factor, citicoline, neurotoxin, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin E, compound brain peptide ganglioside, brain protein, and nervonic acid.

[0047] In the preferred embodiment of the present invention, the traditional Chinese medicine preparation is selected from any one or a combination of the following: Facial Paralysis Pills, Ginseng Rejuvenating Pills, Ginkgo Leaf Tablets or Ginkgo Leaf Extract, Ge Gen Tang combined with Qian Zheng San or its modified formula, Da Qin Jiao Tang or its modified formula, Long Dan Xie Gan Tang combined with Gua Lou Hong Hua Tang or its modified formula, Di Tan Tang combined with Qian Zheng San or its modified formula, Bu Yang Huan Wu Tang combined with Qian Zheng San or its modified formula, Shang Shi Zhi Tong Gao, She Xiang Hu Gu Gao, or a traditional Chinese medicine ointment made from fresh ginger, ginseng, lotus root, yam, licorice, chicory, rose, and angelica.

[0048] In a preferred embodiment of the present invention, the pharmaceutical composition for preventing and treating facial nerve palsy in the recovery period contains any one or a combination of mannitol, sodium aescinate, acyclovir, valacyclovir, dibazol, dexamethasone, prednisone, cytidine diphosphate choline sodium, ginkgo biloba tablets, mouse nerve growth factor, methylcobalamin, and adenosylcobalamin.

[0049] In a preferred embodiment of the present invention, the pharmaceutical composition for preventing and treating facial nerve palsy in the recovery period contains any one or a combination of mannitol, sodium aescinate, acyclovir, valacyclovir, dibazol, dexamethasone, prednisone, cytidine diphosphate choline sodium, ginkgo biloba tablets, mouse nerve growth factor, methylcobalamin, and adenosylcobalamin.

[0050] In a preferred embodiment of the present invention, the pharmaceutical composition for preventing and treating facial nerve palsy in the recovery period consists of a single oral pharmaceutical composition and a single acupoint injection pharmaceutical composition.

[0051] In a preferred embodiment of the present invention, the pharmaceutical composition for single oral administration contains 20-40 mg of sodium aescinate, 10-30 mg of dibazol, 0.5-1.5 mg of methylcobalamin, 0.5-1.5 mg of adenosylcobalamin, 0.2-0.6 g of ginkgo biloba tablets, and 3-6 g of ginseng regeneration pills.

[0052] In a preferred embodiment of the present invention, the administration regimen of the oral pharmaceutical composition is as follows:

[0053] (1) Orally administer sodium aescinate 20mg / time, twice a day, for 1 month;

[0054] (2) Oral administration of dibazol 10mg / time, 3 times / day, for 1 month;

[0055] (3) Oral administration of mecobalamin 0.5 mg / time and adenosylcobalamin 0.5 mg / time, 3 times / day, for 1 month;

[0056] (4) Take 0.2g of Ginkgo biloba tablets orally three times a day for one month;

[0057] (5) Take 3g of Renshen Zaizao Pills orally twice a day for one month.

[0058] In a preferred embodiment of the present invention, the oral pharmaceutical composition is selected from any one or a combination thereof of simultaneous administration or sequential administration.

[0059] In a preferred embodiment of the present invention, the pharmaceutical composition for single acupoint injection contains any one or a combination of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, and 200mg of vitamin B1.

[0060] In a preferred embodiment of the present invention, the drug composition for single acupoint injection consists of 30-90ug of mouse nerve growth factor, 0.5-1.0mg of methylcobalamin, 0.5-1.0mg of adenosylcobalamin, 2-5mg 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%.

[0061] In a preferred embodiment of the present invention, the drug composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 2mg of dexamethasone, and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.

[0062] In a preferred embodiment of the present invention, the drug composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 1.0mg 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%.

[0063] In a preferred embodiment of the present invention, the drug composition for single acupoint injection consists of 90ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone, and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.

[0064] In a preferred embodiment of the present invention, the drug composition for single acupoint injection consists of 60ug of mouse nerve growth factor, 1.0mg 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%.

[0065] In a preferred embodiment of the present invention, the pharmaceutical composition for single acupoint injection optionally contains 100-300 mg of any one or a combination of nerve repair cell protein extracts and / or nerve repair protein compositions with repairing effects.

[0066] In a preferred embodiment of the present invention, the drug composition for single acupoint injection is prepared and used immediately.

[0067] In a preferred embodiment of the present invention, acupoints such as Yangbai, Taiyang, Sibai, Yingxiang, Juliao, Dicang, and Jiache on the affected side of the face are selected for acupoint injection.

[0068] In a preferred embodiment of the present invention, the drug composition for single acupoint injection is injected into the acupoint once a day for 7 days as a course of treatment.

[0069] In the preferred embodiment of the present invention, each acupoint injection treatment is performed for 2-6 courses of treatment, preferably 4-5 courses of treatment.

[0070] In a preferred embodiment of the present invention, the pharmaceutical composition for preventing and treating facial nerve palsy during the recovery period may optionally be used in combination with radiofrequency surgery, rehabilitation exercises, or a combination thereof.

[0071] In a preferred embodiment of the present invention, the radiofrequency surgery is performed at 41℃-42℃, 90V-140V, and 2Hz-6Hz, based on a long-duration temperature-controlled high-voltage variable frequency pulse radiofrequency for 800-1400 seconds.

[0072] In a preferred embodiment of the present invention, the radiofrequency surgery is performed at 41℃-42℃, 100V-120V, and 3Hz-5Hz, based on a long-duration temperature-controlled high-voltage variable frequency pulse radiofrequency for 960-1200 seconds.

[0073] In a preferred embodiment of the present invention, the rehabilitation training exercise is a facial paralysis rehabilitation training exercise created by the inventor (copyright registration number: Guo Zuo Deng Zi-2022-I-10250228 and copyright registration number: Guo Zuo Deng Zi-2022-F-10250229).

[0074] In a preferred embodiment of the present invention, the rehabilitation exercise training is selected from any one or a combination of the first set of rehabilitation exercise training and the second set of rehabilitation exercise training.

[0075] In the preferred embodiment of the present invention, the first set of rehabilitation exercises includes: first, looking in a mirror; second, slowly closing the eyes, closing the eyes for 5 seconds, then opening the eyes and holding for 5 seconds, while controlling the mouth corners to not lift, correcting the associated movements; training the first set of rehabilitation exercises three times a day, with each set being 30 repetitions.

[0076] In the preferred embodiment of the present invention, the second set of rehabilitation exercises includes: first, looking in a mirror; second, opening the eyes and trying to keep the nerve branches silent; and third, pursing the lips, baring the teeth, and puffing out the cheeks around the mouth; and training the first set of rehabilitation exercises three times a day, with each set being trained 10 times.

[0077] In a preferred embodiment of the present invention, the treatment plan for preventing and treating facial nerve palsy during the recovery period includes pulsed radiofrequency surgery, postoperative oral medication and acupoint injection, as well as intraoperative and postoperative rehabilitation exercises.

[0078] In a preferred embodiment of the present invention, the facial nerve palsy is selected from any one or a combination of hemifacial spasm, facial paralysis / related movement, trigeminal neuralgia, glossopharyngeal neuralgia, facial neuritis, peripheral facial paralysis, and oculomotor spasm repair.

[0079] Another object of the present invention is to provide a treatment plan for preventing and treating facial nerve palsy in the recovery period, the treatment plan comprising a pharmaceutical composition for preventing and treating facial nerve palsy in the recovery period, optionally used in combination with radiofrequency surgery, rehabilitation exercises or any combination thereof.

[0080] In a preferred embodiment of the present invention, the pharmaceutical composition for preventing and treating facial nerve palsy in the recovery period contains any one or a combination of dehydrating drugs, antiviral drugs, anti-inflammatory drugs, nerve repair drugs and / or drugs that improve blood circulation, and traditional Chinese medicine preparations.

[0081] In a preferred embodiment of the present invention, the dehydrating agent is selected from any one or a combination of mannitol, sorbitol, aescin, sodium aescinate, and 50% hypertonic glucose solution.

[0082] In a preferred embodiment of the present invention, the antiviral drug is selected from any one or a combination of acyclovir, valacyclovir, dibazol, tadalafil, ribavirin, favipiravir, Paxlovid, molnupiravir, oseltamivir, remdesivir (GS-5734), indinavir, saquinavir, lopinavir, ritonavir, atazanavir, darunavir, telanavir, flushanavir, enzatovir, pretovir, abacavir, erticavir, maribavir, retegvir, ribavirin, amantadine ethylamine, oseltamivir, zanamivir, peramivir, lanimivir, ganciclovir, baloxavir, and nelfinavir.

[0083] In a preferred embodiment of the present invention, the anti-inflammatory drug is selected from any one or a combination of dexamethasone, methylprednisolone, prednisolone, methylprednisolone, cortisone, hydrocortisone, prednisolone, and prednisolone.

[0084] In a preferred embodiment of the present invention, the nerve repair drug and / or blood circulation improving drug is selected from any one or a combination of mouse nerve growth factor, monosialotetrahexosylganglioside (GM1), cerebrolysin, methylcobalamin, adenosylcobalamin, compound vitamin B, butylphthalide, cinnarizine maleate, edaravone, edaravone dexborneol, citicoline, citicoline sodium, ganglioside, piracetam, piracetam, piracetam, nerve growth factor, citicoline, neurotoxin, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin E, compound brain peptide ganglioside, brain protein, and nervonic acid.

[0085] In the preferred embodiment of the present invention, the traditional Chinese medicine preparation is selected from any one or a combination of the following: Facial Paralysis Pills, Ginseng Rejuvenating Pills, Ginkgo Leaf Tablets or Ginkgo Leaf Extract, Ge Gen Tang combined with Qian Zheng San or its modified formula, Da Qin Jiao Tang or its modified formula, Long Dan Xie Gan Tang combined with Gua Lou Hong Hua Tang or its modified formula, Di Tan Tang combined with Qian Zheng San or its modified formula, Bu Yang Huan Wu Tang combined with Qian Zheng San or its modified formula, Shang Shi Zhi Tong Gao, She Xiang Hu Gu Gao, or a traditional Chinese medicine ointment made from fresh ginger, ginseng, lotus root, yam, licorice, chicory, rose, and angelica.

[0086] In a preferred embodiment of the present invention, the pharmaceutical composition for preventing and treating facial nerve palsy in the recovery period contains any one or a combination of mannitol, sodium aescinate, acyclovir, valacyclovir, dibazol, dexamethasone, prednisone, cytidine diphosphate choline sodium, ginkgo biloba tablets, mouse nerve growth factor, methylcobalamin, and adenosylcobalamin.

[0087] In a preferred embodiment of the present invention, the pharmaceutical composition for preventing and treating facial nerve palsy in the recovery period contains any one or a combination of mannitol, sodium aescinate, acyclovir, valacyclovir, dibazol, dexamethasone, prednisone, cytidine diphosphate choline sodium, ginkgo biloba tablets, mouse nerve growth factor, methylcobalamin, and adenosylcobalamin.

[0088] In a preferred embodiment of the present invention, the pharmaceutical composition for preventing and treating facial nerve palsy in the recovery period consists of a single oral pharmaceutical composition and a single acupoint injection pharmaceutical composition.

[0089] In a preferred embodiment of the present invention, the pharmaceutical composition for single oral administration contains 20-40 mg of sodium aescinate, 10-30 mg of dibazol, 0.5-1.5 mg of methylcobalamin, 0.5-1.5 mg of adenosylcobalamin, 0.2-0.6 g of ginkgo biloba tablets, and 3-6 g of ginseng regeneration pills.

[0090] In a preferred embodiment of the present invention, the administration regimen of the oral pharmaceutical composition is as follows:

[0091] (1) Orally administer sodium aescinate 20mg / time, twice a day, for 1 month;

[0092] (2) Oral administration of dibazol 10mg / time, 3 times / day, for 1 month;

[0093] (3) Oral administration of mecobalamin 0.5 mg / time and adenosylcobalamin 0.5 mg / time, 3 times / day, for 1 month;

[0094] (4) Take 0.2g of Ginkgo biloba tablets orally three times a day for one month;

[0095] (5) Take 3g of Renshen Zaizao Pills orally twice a day for one month.

[0096] In a preferred embodiment of the present invention, the oral pharmaceutical composition is selected from any one or a combination thereof of simultaneous administration or sequential administration.

[0097] In a preferred embodiment of the present invention, the pharmaceutical composition for single acupoint injection contains any one or a combination of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, and 200mg of vitamin B1.

[0098] In a preferred embodiment of the present invention, the drug composition for single acupoint injection consists of 30-90ug of mouse nerve growth factor, 0.5-1.0mg of methylcobalamin, 0.5-1.0mg of adenosylcobalamin, 2-5mg 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%.

[0099] In a preferred embodiment of the present invention, the drug composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 2mg of dexamethasone, and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.

[0100] In a preferred embodiment of the present invention, the drug composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 1.0mg 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%.

[0101] In a preferred embodiment of the present invention, the drug composition for single acupoint injection consists of 90ug of mouse nerve growth factor, 1.0mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone, and 1ml of lidocaine hydrochloride, wherein the concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, and 2%.

[0102] In a preferred embodiment of the present invention, the drug composition for single acupoint injection consists of 60ug of mouse nerve growth factor, 1.0mg 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%.

[0103] In a preferred embodiment of the present invention, the pharmaceutical composition for single acupoint injection optionally contains 100-300 mg of any one or a combination of nerve repair cell protein extracts and / or nerve repair protein compositions with repairing effects.

[0104] In a preferred embodiment of the present invention, the drug composition for single acupoint injection is prepared and used immediately.

[0105] In a preferred embodiment of the present invention, acupoints such as Yangbai, Taiyang, Sibai, Yingxiang, Juliao, Dicang, and Jiache on the affected side of the face are selected for acupoint injection.

[0106] In a preferred embodiment of the present invention, the drug composition for single acupoint injection is injected into the acupoint once a day for 7 days as a course of treatment.

[0107] In the preferred embodiment of the present invention, each acupoint injection treatment is performed for 2-6 courses of treatment, preferably 4-5 courses of treatment.

[0108] In a preferred embodiment of the present invention, the radiofrequency surgery is performed at 41℃-42℃, 90V-140V, and 2Hz-6Hz, based on a long-duration temperature-controlled high-voltage variable frequency pulse radiofrequency for 800-1400 seconds.

[0109] In a preferred embodiment of the present invention, the radiofrequency surgery is performed at 41℃-42℃, 100V-120V, and 3Hz-5Hz, based on a long-duration temperature-controlled high-voltage variable frequency pulse radiofrequency for 960-1200 seconds.

[0110] In a preferred embodiment of the present invention, the rehabilitation training exercise is a facial paralysis rehabilitation training exercise created by the inventor (copyright registration number: Guo Zuo Deng Zi-2022-I-10250228 and copyright registration number: Guo Zuo Deng Zi-2022-F-10250229).

[0111] In a preferred embodiment of the present invention, the rehabilitation exercise training is selected from any one or a combination of the first set of rehabilitation exercise training and the second set of rehabilitation exercise training.

[0112] In the preferred embodiment of the present invention, the first set of rehabilitation exercises includes: first, looking in a mirror; second, slowly closing the eyes, closing the eyes for 5 seconds, then opening the eyes and holding for 5 seconds, while controlling the mouth corners to not lift, correcting the associated movements; training the first set of rehabilitation exercises three times a day, with each set being 30 repetitions.

[0113] In the preferred embodiment of the present invention, the second set of rehabilitation exercises includes: first, looking in a mirror; second, opening the eyes and trying to keep the nerve branches silent; and third, pursing the lips, baring the teeth, and puffing out the cheeks around the mouth; and training the first set of rehabilitation exercises three times a day, with each set being trained 10 times.

[0114] In a preferred embodiment of the present invention, the treatment plan for preventing and treating facial nerve palsy during the recovery period includes pulsed radiofrequency surgery, postoperative oral medication and acupoint injection, as well as intraoperative and postoperative rehabilitation exercises.

[0115] In a preferred embodiment of the present invention, the facial nerve palsy is selected from any one or a combination of hemifacial spasm, facial paralysis / related movement, trigeminal neuralgia, glossopharyngeal neuralgia, facial neuritis, peripheral facial paralysis, and oculomotor spasm repair.

[0116] To clearly describe the present invention, the nerve repair cell protein extract or nerve repair cell protein composition with repair function described in the present invention was prepared in accordance with the patent applications (CN2023100429139, PCT / CN2023 / 073566, CN2023100429143, PCT / CN2023 / 073582).

[0117] In a preferred embodiment of the present invention, the method for preparing the nerve repair cell protein extract with nerve repair efficacy includes the following steps:

[0118] S-1: A density of 5.0 × 10⁻⁶ 6 5.0 × 10⁻⁵ cells / mL 7 Mesenchymal stem cells per mL were placed in a culture medium containing 40-50% DMEM / F12, 40-50% RPMI1640, 0.1-2% bovine serum albumin (BSA), 1-15 μg / mL epidermal growth factor (EGF), 1-15 μg / mL fibroblast growth factor (FGF), 1-15 μg / mL insulin transferrin, 0.01-0.1% compound amino acids (18AA), and 2-10 μmol / L of stress. After culturing at 37.0℃±0.5℃ and 5%±1.0% CO2 for 2-6 hours, the cells were separated, washed, and collected. The stress was selected from any one of compounds 1-16 or a combination thereof.

[0119]

[0120]

[0121] S-2: Collect cells at a density of 5.0 × 10⁻⁶. 6 5.0 × 10⁻⁵ cells / mL 7Cells / mL are dispersed in a solvent and then sonicated at 2℃-8℃ to obtain cell lysis buffer. The solvent is selected from any one or a combination of physiological saline, 5% glucose solution, phosphate buffer (PBS), TBPS buffer, TBST buffer, and Tris buffer.

[0122] S-3: After separating the cell lysate obtained in step S-2, the resulting separation solution is filtered sequentially through 0.45um and 0.22um filter membranes to obtain the final product.

[0123] In a preferred embodiment of the present invention, the culture medium in step S-1 contains 42-45% DMEM / F12, 42-45% RPMI 1640, 0.5-1.5% bovine serum albumin (BSA), 5-10 ug / mL epidermal growth factor (EGF), 5-10 ug / mL fibroblast growth factor (FGF), 5-10 ug / mL insulin transferrin, 0.02-0.05% compound amino acids (18AA), and 3-8 μmol / L of stressants.

[0124] In a preferred embodiment of the present invention, the culture medium in step S-1 contains 45% DMEM / F12, 45% RPMI 1640, 0.5% bovine serum albumin (BSA), 10ug / mL epidermal growth factor (EGF), 10ug / mL fibroblast growth factor (FGF), 10ug / mL insulin transferrin, 0.05% compound amino acids (18AA), and 4-6μmol / L of stressants.

[0125] In a preferred embodiment of the present invention, the density of mesenchymal stem cells in step S-1 is 8.0 × 10⁻⁶. 6 -2.0×10 7 Cells / mL, preferably 8.0 × 10⁻⁶. 6 -1.0×10 7 per mL.

[0126] In a preferred embodiment of the present invention, the mesenchymal stem cells in step S-1 are cultured in a culture medium for 3-5 hours, preferably 3.5-4.5 hours.

[0127] In a preferred embodiment of the present invention, the solvent for washing cells in step S-1 is selected from any one or a combination of physiological saline, 5% glucose solution, phosphate buffer (PBS), TBPS buffer, TBST buffer, and Tris buffer, and the number of cell washings is 2-5 times, preferably 3-4 times.

[0128] In a preferred embodiment of the present invention, the separation in step S-1 is selected from any one or a combination of centrifugation and filtration, wherein the centrifugation conditions are 1000-2000 rpm for 3-15 min, preferably 1200-1500 rpm for 5-10 min.

[0129] In the preferred embodiment of the present invention, the ultrasonic conditions in step S-2 are: working for 3 seconds at 2℃-8℃, 25kHz, and 360W, followed by a 1-second interval, and ultrasonic treatment for 1-5 minutes.

[0130] In the preferred embodiment of the present invention, the separation in step S-3 is selected from any one or a combination of centrifugation at 2000-8000 rpm for 10-30 min, multi-stage centrifugation, and multi-stage filtration, preferably 3000-7000 rpm for 15-25 min.

[0131] In the preferred embodiment of the present invention, the multi-stage centrifugation in step S-3 is performed sequentially at 3000-4000 rpm for 3-5 min, 5000-6000 rpm for 3-5 min, and 7000 rpm for 5-8 min.

[0132] In a preferred embodiment of the present invention, the pore size of the filter membrane for multi-stage filtration is selected from any one of 80um, 50um, 30um, 10um, and 5um.

[0133] In a preferred embodiment of the present invention, the cell protein extract obtained in step S-3 is cryopreserved, preferably at -40°C to -20°C.

[0134] In a preferred embodiment of the present invention, the cell protein extract obtained in step S-3 is digested by either a nuclease or a totipotent nuclease and then separated and purified.

[0135] In a preferred embodiment of the present invention, the culture of the mesenchymal passaged stem cells or the culture of primary mesenchymal stem cells adopts a culture method in the art.

[0136] In a preferred embodiment of the present invention, the culture of the mesenchymal stem cells includes the following steps: primary mesenchymal stem cells are cultured at an initial density of 5.0 × 10⁻⁶. 5 -5.0×10 6 Add cells / ml to the passage medium and incubate at 37.0℃±0.5℃ and 5%±1.0%CO2 for 10-15 days. Every 2-3 days, observe the passage medium until it turns yellow, and replace half of the passage medium. The passage medium is DMEM / F12 medium containing 10% FBS, 100U / ml penicillin and 100ug / ml streptomycin.

[0137] In a preferred embodiment of the present invention, the culture of the primary mesenchymal stem cells includes the following steps:

[0138] 1) After cleaning and disinfecting the umbilical cord, perform tissue dissection, take Wharton's jelly tissue, and cut it into 3mm pieces. 3 Small pieces of tissue were centrifuged, washed, and collected. The tissue pieces were then placed in DMEM / F12 medium containing 10% fetal bovine serum (FBS), 100 μg / ml penicillin, and 100 μg / ml streptomycin. The medium was then cultured at 37.0℃±0.5℃ and 5%±1.0% CO2. The medium was replaced in half every 2-3 days until the tissue pieces crawled out of the cells.

[0139] 2) Shake, collect the lower layer of cells, wash with PBS, add 0.25% trypsin to digest for 2-3 minutes, add an equal volume of trypsin stop solution to stop digestion, gently pipette, centrifuge at 1200-1500 rpm / min for 5-8 minutes, collect the cells, and you have obtained the product.

[0140] Unless otherwise stated, when this invention relates to percentages between liquids, the percentage is volume / volume percentage; when this invention relates to percentages between liquids and solids, the percentage is volume / weight percentage; when this invention relates to percentages between solids and liquids, the percentage is weight / volume percentage; the remainder is weight / weight percentage.

[0141] Unless otherwise stated, the present invention is evaluated using the following methods:

[0142] 1. Location of acupoints: The acupoints are located according to the national standard of the People's Republic of China "Names and Locations of Acupoints" (GB / T 12345-2006) issued by the State Bureau of Technical Supervision.

[0143] 2. Facial paralysis motor function evaluation scale;

[0144] 3. Facial paralysis quality of life assessment scale.

[0145] Compared with the prior art, the present invention has the following beneficial effects:

[0146] 1. This invention provides a scientifically formulated drug composition for treating facial paralysis in the recovery period. It employs simultaneous and / or sequential administration to treat the affected side, which helps reduce facial edema, eliminate inflammation at the site of facial paralysis, nourish the damaged nerves, and repair damaged myelin sheaths and axons. The dehydrating agents in the drug composition eliminate facial edema, reducing or even eliminating facial nerve damage caused by edema; the antiviral agents fight viruses, eliminate the causes of facial paralysis, and promote nerve regeneration; the anti-inflammatory agents clear inflammatory factors related to facial paralysis, facilitating the elimination of inflammation and edema; the nerve repair agents and / or blood circulation improving agents improve blood circulation disorders caused by facial edema, viruses, and inflammation, and repair facial nerve damage caused by these factors, promoting nerve nutrition and myelin sheath and axon repair; the traditional Chinese medicine preparations dispel wind and phlegm, invigorate blood circulation, and promote the treatment, rehabilitation, and prognosis of facial paralysis in the recovery period.

[0147] 2. The combination of the drug composition of the present invention with radiofrequency surgery and rehabilitation exercises has the advantages of synergistic effect, rapid onset of action, high efficacy, high cure rate, virtually no side effects and virtually no recurrence rate, which significantly improves the treatment prognosis and quality of life of patients. Detailed Implementation

[0148] The following detailed explanation and description of the present invention, in conjunction with specific embodiments, does not limit the scope of protection of the present invention.

[0149] Example 1 Preparation of nerve repair cell protein extracts with repairing effects

[0150] 1. Culture of primary mesenchymal stem cells

[0151] The culture of primary mesenchymal stem cells includes the following steps:

[0152] 1) After cleaning and disinfecting the umbilical cord, perform tissue dissection, take Wharton's jelly tissue, and cut it into 3mm pieces. 3 Small pieces of tissue were centrifuged, washed, and collected. The tissue pieces were placed in culture flasks and DMEM / F12 medium containing 10% fetal bovine serum (FBS), 100 μg / ml penicillin, and 100 μg / ml streptomycin were added. The flasks were then incubated at 37°C and 5% CO2 to promote adhesion. Every 2-3 days, the medium was observed to turn yellow. Half of the medium was replaced and the flasks were incubated for 10-12 days until cells could be seen crawling out from the edges of the tissue pieces.

[0153] 2) Gently shake to dislodge the tissue block, and collect the tissue block and lower layer cells separately. The collected tissue block is then cultured on a separate wall.

[0154] 3) After washing the collected low-layer cells with PBS, add an appropriate amount of 0.25% trypsin to digest for 2-3 minutes, add an equal volume of trypsin stop solution to stop digestion, gently blow the bottom of the bottle with a pipette, centrifuge at 1500 rpm for 5 minutes, and collect the cells.

[0155] 2. Passaging of primary mesenchymal stem cells (culture of passaged mesenchymal stem cells)

[0156] Passaging of primary mesenchymal stem cells (culture of passaged mesenchymal stem cells): Primary mesenchymal stem cells were cultured at an initial density of 5.0 × 10⁻⁶. 5 -5.0×10 6 Add cells / ml to DMEM / F12 medium containing 10% FBS, 100U / ml penicillin and 100ug / ml streptomycin, and then incubate at 37.0℃±0.5℃ and 5%±1.0% CO2 for 10-15 days. Every 2-3 days, observe the medium until it turns yellow, and then replace half of the medium.

[0157] 3. The preparation of compounds 1-16 was carried out in accordance with reference 1 (New limonophyllines AC from the stem of Atalantia monophylla and cytotoxicity against cholangiocarcinoma and HepG2cell lines, Arch. Pharm. Res. (2018) 41: 431–437).

[0158] A method for preparing a nerve repair cell protein extract with nerve repair effects includes the following steps:

[0159] (1) Mesenchymal cells were passaged at a density of 8.0 × 10⁶ cells / year. 6 Cells were added at a concentration of 45% DMEM / F12, 45% RPMI1640, 0.5% bovine serum albumin (BSA), 10 μg / mL epidermal growth factor (EGF), 10 μg / mL fibroblast growth factor (FGF), 10 μg / mL insulin transferrin, 0.05% compound amino acids (18AA), and 5 μmol / L of compound 16 to a culture medium. The cells were then incubated at 37°C and 5% CO2 for 4 h. After centrifugation at 1200 rpm for 5 min, the cells were washed three times with PBS and collected.

[0160] (2) Arrange the cells collected in step (1) at a density of 1.0 × 10⁻⁶. 7Cells / mL were dispersed in physiological saline and sonicated for 3 seconds with a 1-second interval for 2 minutes at 2-8℃, 25kHz and 360W to obtain cell lysis buffer.

[0161] (3) Centrifuge the cell lysate obtained in step (2) at 7000 rpm for 20 min, and filter the resulting centrifuged liquid through 0.45 μm and 0.22 μm filter membranes in sequence to obtain cell protein extract.

[0162] (4) Add the required amount of mannitol to the cell protein extract obtained in step (3), stir, mix evenly, and freeze dry. The resulting freeze-dried preparation contains 5% mannitol (m / m).

[0163] Experimental Example 1 Study on the therapeutic effect of the pharmaceutical composition of the present invention on facial paralysis in the recovery period

[0164] Seventy patients with facial paralysis in the recovery period were selected and divided into three groups: Group 1 (n=10), Group 2 (n=40), and Group 3 (n=20). Inclusion criteria: meeting the diagnostic criteria for facial neuritis according to both Traditional Chinese Medicine and Western Medicine; onset of symptoms within 15 days to 6 months; age 20-70 years; HB grade II or higher; informed consent; and good compliance. Exclusion criteria: complete severance or absence of the facial nerve; infection or skin injury at the puncture site; local tumors or other space-occupying lesions affecting the facial nerve; coagulation disorders, which may increase the risk of bleeding or hematoma; implanted pacemakers, which may interfere with the normal function of the pacemaker; pregnant or lactating women, which may affect the health of the fetus or infant; allergies to the electrode needles or local anesthetics, which may cause allergic reactions or other adverse reactions; and patients with mental disorders or who cannot cooperate with rehabilitation or corrective training.

[0165] Treatment regimen for Group 1 (7 days per course, 4 courses): The single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, and 200mg of vitamin B1. Prepare and use immediately. Select the Yangbai, Taiyang, Sibai, Yingxiang, Juliao, Dicang, and Jiache acupoints on the affected side of the face for acupoint injection, once a day.

[0166] The treatment regimens for the two groups (7 days per course, 4 courses of treatment) included pulsed radiofrequency surgery, postoperative oral medication and acupoint injection, as well as intraoperative and postoperative rehabilitation exercises.

[0167] 1. Pulsed Radiofrequency Surgery: A radiofrequency temperature-controlled thermocoagulator (model R-2000B M1, purchased from Beiqi Medical) is used to perform nerve activation, repair, and micro-correction surgery on the lesion site based on long-term temperature-controlled high-voltage variable frequency pulsed radiofrequency technology (pulse width 20ms, resting period 480ms, maximum voltage 100V, pulse frequency 2HZ). The pulsed radiofrequency is performed for 1200 seconds under the conditions of 41-42℃, 90-140V, and 2-5Hz. During the surgery, two sets of facial movements are performed, including keeping the eyes wide open, repeatedly grinning, and repeatedly puffing out the cheeks.

[0168] 2. Postoperative oral medication administration regimens, including concurrent and / or sequential administration:

[0169] (1) Orally administer sodium aescinate 20mg / time, twice a day, for 1 month;

[0170] (2) Oral administration of dibazol 10mg / time, 3 times / day, for 1 month;

[0171] (3) Oral administration of mecobalamin 0.5 mg / time and adenosylcobalamin 0.5 mg / time, 3 times / day, for 1 month;

[0172] (4) Take 0.2g of Ginkgo biloba tablets orally three times a day for one month;

[0173] (5) Take 3g of Renshen Zaizao Pills orally twice a day for one month.

[0174] 3. Postoperative acupoint injection administration regimen:

[0175] The drug 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. It should be prepared and used immediately. Acupoints such as Yangbai, Taiyang, Sibai, Yingxiang, Juliao, Dicang, and Jiache on the affected side of the face should be selected for acupoint injection once a day.

[0176] 4. Postoperative rehabilitation exercises:

[0177] The first set of rehabilitation exercises: 1. Look in a mirror; 2. Slowly close your eyes, hold for 5 seconds, then open them and hold for 5 seconds, while controlling to prevent the corners of your mouth from lifting upwards, correcting any related movements. Perform three sets daily, 30 repetitions per set. The second set of rehabilitation exercises: 1. Look in a mirror; 2. Open your eyes, trying to keep the nerve branches still; 3. Pout, grin, and puff out your cheeks around your mouth. Perform three sets daily, 10 repetitions per set.

[0178] The treatment regimens for the three groups (7 days per course, 4 courses of treatment) included pulsed radiofrequency surgery, postoperative oral medication and acupoint injection, as well as intraoperative and postoperative rehabilitation exercises.

[0179] 1. Pulsed Radiofrequency Surgery: A radiofrequency temperature-controlled thermocoagulator (model R-2000B M1, purchased from Beiqi Medical) is used to perform nerve activation, repair, and micro-correction surgery on the lesion site based on long-term temperature-controlled high-voltage variable frequency pulsed radiofrequency technology (pulse width 20ms, resting period 480ms, maximum voltage 100V, pulse frequency 2HZ). The pulsed radiofrequency is performed for 1200 seconds under the conditions of 41-42℃, 90-140V, and 2-5Hz. During the surgery, two sets of facial movements are performed, including keeping the eyes wide open, repeatedly grinning, and repeatedly puffing out the cheeks.

[0180] 2. Postoperative oral medication administration regimens, including concurrent and / or sequential administration:

[0181] (1) Orally administer sodium aescinate 20mg / time, twice a day, for 1 month;

[0182] (2) Oral administration of dibazol 10mg / time, 3 times / day, for 1 month;

[0183] (3) Oral administration of mecobalamin 0.5 mg / time and adenosylcobalamin 0.5 mg / time, 3 times / day, for 1 month;

[0184] (4) Take 0.2g of Ginkgo biloba tablets orally three times a day for one month;

[0185] (5) Take 3g of Renshen Zaizao Pills orally twice a day for one month;

[0186] 3. Postoperative acupoint injection administration regimen:

[0187] (1) The drug composition for single acupoint injection consists of 30ug of mouse nerve growth factor, 0.5mg of methylcobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride. It should be prepared and used immediately. Select the Yangbai, Taiyang, Sibai, Yingxiang, Juliao, Dicang and Jiache acupoints on the affected side of the face for acupoint injection. Acupoint injection is performed once a day.

[0188] (2) 130ug of the freeze-dried preparation of nerve repair cell protein extract prepared in Example 1 was dissolved in 2ml of physiological saline. The Yangbai, Taiyang, Sibai, Yingxiang, Juliao, Dicang and Jiache acupoints on the affected side of the face, the Taiyang and Dicang acupoints on the opposite side, and the Hegu acupoints on both hands were selected for acupoint injection. The acupoint injection was performed once a day.

[0189] 4. Rehabilitation exercises:

[0190] The first set of rehabilitation exercises includes: 1. Looking in a mirror; 2. Slowly closing your eyes for 5 seconds, then opening them and holding for 5 seconds, while controlling the corners of your mouth to avoid lifting upwards, correcting any related movements. Perform three sets daily, 30 repetitions per set. The second set of rehabilitation exercises includes: 1. Looking in a mirror; 2. Keeping your eyes open and trying to remain silent on nerve branches; 3. Pouting, baring teeth, and puffing out your cheeks around your mouth. Perform three sets daily, 10 repetitions per set.

[0191] Therapeutic effect assessment: Satisfaction survey and clinical scoring House-Brakmann facial nerve functional grading efficacy evaluation form.

[0192]

[0193]

[0194] Group 1: After 3 days of treatment, approximately 50% of patients experienced improvement in facial muscles; after 28 days of treatment, the effectiveness rate was 70%.

[0195] Group 2: After 3 days of treatment, approximately 60% of patients experienced improvement in facial muscles; after 7 days of treatment, the effectiveness rate was 80%. After 28 days of treatment, the cure rate was approximately 90%. Patients who followed medical advice and took precautions to reduce or avoid factors such as staying up late, fatigue, external infections, and exposure to cold experienced virtually no recurrence and a significant improvement in their quality of life.

[0196] Group 3: After 3 days of treatment, approximately 80% of patients experienced improvement in facial muscles, and the effectiveness rate was 90% after 7 days of treatment. The cure rate after 28 days of treatment was approximately 95%. Patients who followed medical advice and took precautions to reduce or even avoid the effects of factors such as staying up late, fatigue, external infections, and catching a cold experienced virtually no recurrence and a significant improvement in their quality of life.

[0197] The above description of specific embodiments of the present invention does not limit the present invention. Those skilled in the art can make various changes or modifications based on the present invention, and as long as they do not depart from the spirit of the present invention, they should all fall within the scope of protection of the claims of the present invention.

Claims

1. A pharmaceutical composition for preventing and treating facial nerve palsy in the recovery period, said pharmaceutical composition comprising sodium aescinate, dibazol, ginkgo biloba tablets, mouse nerve growth factor, methylcobalamin, adenosylcobalamin, ginseng regeneration pills, vitamin B1, and a nerve repair cell protein extract with nerve repair effects. The preparation method of the nerve repair cell protein extract with nerve repair efficacy includes the following steps: S-1: A density of 5.0 × 10⁻⁶ 6 5.0 × 10⁻⁵ cells / mL 7 Mesenchymal stem cells (MSCs) at a density of 40-50% / mL were placed in a culture medium containing 40-50% DMEM / F12, 40-50% RPMI 1640, 0.1-2% bovine serum albumin (BSA), 1-15 μg / mL epidermal growth factor (EGF), 1-15 μg / mL fibroblast growth factor (FGF), 1-15 μg / mL insulin transferrin, 0.01-0.1% compound amino acids (18AA), and 2-10 μmol / L stressant. After culturing at 37.0℃±0.5℃ and 5%±1.0% CO2 for 2-6 hours, the cells were separated, washed, and collected. The stressor is compound 16: ； S-2: Collect cells at a density of 5.0 × 10⁻⁶. 6 5.0 × 10⁻⁵ cells / mL 7 Cells / mL are dispersed in a solvent and then sonicated at 2℃-8℃ to obtain cell lysis buffer. The solvent is selected from any one or a combination of physiological saline, 5% glucose solution, phosphate buffer (PBS), TBPS buffer, TBST buffer, and Tris buffer. S-3: After separating the cell lysate obtained in step S-2, the resulting separation solution is filtered sequentially through 0.45 μm and 0.22 μm filter membranes to obtain the final product.

2. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition for preventing and treating facial nerve palsy in the recovery period comprises a single oral pharmaceutical composition and a single acupoint injection pharmaceutical composition.

3. The pharmaceutical composition according to claim 2, wherein the single-dose oral pharmaceutical composition comprises 20-40 mg of sodium aescinate, 10-30 mg of dibazol, 0.5-1.5 mg of methylcobalamin, 0.5-1.5 mg of adenosylcobalamin, 0.2-0.6 g of ginkgo biloba tablets, and 3-6 g of ginseng regeneration pills.

4. The dosage regimen of the oral pharmaceutical composition as described in claim 3 is as follows: (1) Oral administration of sodium aescinate 20mg / time, twice a day, for 1 month; (2) Oral administration of dibazol 10mg / time, 3 times / day, for 1 month; (3) Oral administration of mecobalamin 0.5 mg / time and adenosylcobalamin 0.5 mg / time, 3 times / day, for 1 month; (4) Take 0.2g of Ginkgo biloba tablets orally three times a day for one month; (5) Take 3g of Renshen Zaizao Pills orally twice a day for one month.

5. The pharmaceutical composition of claim 2, wherein the oral pharmaceutical composition is selected from any one or a combination thereof of simultaneous or sequential administration.

6. The pharmaceutical composition of claim 2, wherein the pharmaceutical composition for single acupoint injection contains any one or a combination of 30 μg of mouse nerve growth factor, 0.5 mg of methylcobalamin, and 200 mg of vitamin B1.

7. The pharmaceutical composition according to claim 2, wherein the pharmaceutical composition for single acupoint injection comprises 30-90 μg of mouse nerve growth factor, 0.5-1.0 mg of methylcobalamin, 0.5-1.0 mg of adenosylcobalamin, 2-5 mg of dexamethasone, and 1 ml of lidocaine hydrochloride, wherein, The concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, or 2%.

8. The pharmaceutical composition of claim 7, wherein the pharmaceutical composition for single acupoint injection comprises 30 μg of mouse nerve growth factor, 0.5 mg of methylcobalamin, 0.5 mg of adenosylcobalamin, 2 mg of dexamethasone, and 1 ml of lidocaine hydrochloride, wherein, The concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, or 2%.

9. The pharmaceutical composition of claim 7, wherein the pharmaceutical composition for single acupoint injection comprises 30 μg of mouse nerve growth factor, 0.5 mg of methylcobalamin, 1.0 mg of adenosylcobalamin, 5 mg of dexamethasone, and 1 ml of lidocaine hydrochloride, wherein, The concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, or 2%.

10. The pharmaceutical composition of claim 7, wherein the pharmaceutical composition for single acupoint injection comprises 90 μg of mouse nerve growth factor, 1.0 mg of methylcobalamin, 0.5 mg of adenosylcobalamin, 5 mg of dexamethasone, and 1 ml of lidocaine hydrochloride, wherein, The concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, or 2%.

11. The pharmaceutical composition of claim 7, wherein the pharmaceutical composition for single acupoint injection comprises 60 μg of mouse nerve growth factor, 1.0 mg of methylcobalamin, 0.5 mg of adenosylcobalamin, 3 mg of dexamethasone, and 1 ml of lidocaine hydrochloride, wherein, The concentration of lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5%, or 2%.

12. The pharmaceutical composition according to any one of claims 2-11, wherein the pharmaceutical composition for single acupoint injection optionally contains 100-300 mg of a nerve repair cell protein extract with repairing effects.

13. The pharmaceutical composition according to any one of claims 2-11, wherein the pharmaceutical composition for single acupoint injection is prepared and used immediately.

14. The pharmaceutical composition according to any one of claims 1-11, wherein the acupoints Yangbai, Taiyang, Sibai, Yingxiang, Juliao, Dicang and Jiache on the affected side of the face are selected for acupoint injection.

15. The pharmaceutical composition according to any one of claims 1-11, wherein the pharmaceutical composition for single acupoint injection is injected into the acupoint once a day for 7 days as a course of treatment.

16. The pharmaceutical composition as described in claim 15, wherein each acupoint injection treatment lasts for 2-6 courses of treatment.

17. The pharmaceutical composition as described in claim 16, wherein each acupoint injection treatment lasts for 4-5 courses of treatment.

18. The pharmaceutical composition of claim 1, wherein the culture medium in step S-1 contains 42-45% DMEM / F12, 42-45% RPMI1640, 0.5-1.5% bovine serum albumin (BSA), 5-10 μg / mL epidermal growth factor (EGF), 5-10 μg / mL fibroblast growth factor (FGF), 5-10 μg / mL insulin transferrin, 0.02-0.05% compound amino acids (18AA), and 3-8 μmol / L of stressants.

19. The pharmaceutical composition of claim 18, wherein the culture medium in step S-1 contains 45% DMEM / F12, 45% RPMI1640, 0.5% bovine serum albumin (BSA), 10 μg / mL epidermal growth factor (EGF), 10 μg / mL fibroblast growth factor (FGF), 10 μg / mL insulin transferrin, 0.05% compound amino acids (18AA), and 4-6 μmol / L of stressants.

20. The pharmaceutical composition of claim 1, wherein the density of mesenchymal stem cells in step S-1 is 8.0 × 10⁻⁶. 6 -2.0×10 7 per mL.

21. The pharmaceutical composition of claim 20, wherein the density of mesenchymal stem cells in step S-1 is 8.0 × 10⁻⁶. 6 -1.0×10 7 per mL.

22. The pharmaceutical composition of claim 1, wherein the mesenchymal stem cells of step S-1 are cultured in a culture medium for 3-5 hours.

23. The pharmaceutical composition of claim 22, wherein the mesenchymal stem cells of step S-1 are cultured in a culture medium for 3.5-4.5 hours.

24. The pharmaceutical composition of claim 1, wherein the solvent for washing cells in step S-1 is selected from any one or a combination of physiological saline, 5% glucose solution, phosphate buffer (PBS), TBPS buffer, TBST buffer, and Tris buffer, and the number of cell washing cycles is 2-5.

25. The pharmaceutical composition of claim 24, wherein the number of cell washing cycles in step S-1 is 3-4.

26. The pharmaceutical composition of claim 1, wherein the separation in step S-1 is selected from any one or a combination of centrifugation and filtration, wherein, The centrifugation conditions are 1000-2000 rpm for 3-15 minutes.

27. The pharmaceutical composition of claim 26, wherein the separation in step S-1 is selected from any one or a combination of centrifugation, filtration, etc., wherein, The centrifugation conditions are 1200rpm-1500rpm for 5-10min.

28. The pharmaceutical composition according to claim 1, wherein the ultrasonic conditions in step S-2 are: working for 3 seconds at 2℃-8℃, 25kHz, and 360W, followed by a 1-second interval, and ultrasonic treatment for 1-5 minutes.

29. The pharmaceutical composition of claim 1, wherein the separation in step S-3 is selected from any one or a combination thereof, such as centrifugation at 2000-8000 rpm for 10-30 min, multi-stage centrifugation, or multi-stage filtration.

30. The pharmaceutical composition of claim 29, wherein the separation in step S-3 is performed by centrifugation at 3000-7000 rpm for 15-25 min.

31. The pharmaceutical composition of claim 29, wherein the multi-stage centrifugation in step S-3 is performed sequentially at 3000-4000 rpm for 3-5 min, 5000-6000 rpm for 3-5 min, and 7000 rpm for 5-8 min.

32. The pharmaceutical composition of claim 29, wherein the pore size of the multi-stage filtration membrane is selected from any one of 80 μm, 50 μm, 30 μm, 10 μm, and 5 μm.

33. The pharmaceutical composition of claim 1, wherein the cell protein extract obtained in step S-3 is cryopreserved.

34. The pharmaceutical composition of claim 33, wherein the cell protein extract obtained in step S-3 is frozen at -40°C to -20°C.

35. The pharmaceutical composition of claim 1, wherein the cell protein extract obtained in step S-3 is enzymatically hydrolyzed by any one of a nuclease or a totipotent nuclease and then separated and purified.

36. The pharmaceutical composition of claim 1, wherein the culture of the mesenchymal stem cells or the culture of primary mesenchymal stem cells is performed using culture methods in the art.

37. The pharmaceutical composition of claim 36, wherein culturing the mesenchymal stem cells comprises the following steps: culturing primary mesenchymal stem cells at an initial density of 5.0 × 10⁻⁶. 5 -5.0×10 6 Add cells / ml to the subculture medium, then incubate at 37.0℃±0.5℃ and 5%±1.0% CO2 for 10-15 days. Every 2-3 days, observe the subculture medium; when it turns yellow, replace half of the medium. The passage medium contained 10% FBS, 100 U / ml penicillin and 100 ug / ml streptomycin in DMEM / F12 medium.

38. The pharmaceutical composition of claim 37, wherein the culture of the primary mesenchymal stem cells comprises the following steps: 1) After cleaning and disinfecting the umbilical cord, perform tissue dissection, take Wharton's jelly tissue, and cut it into 3mm pieces. 3 Small pieces of tissue were centrifuged, washed, and collected. The tissue pieces were then placed in DMEM / F12 medium containing 10% fetal bovine serum (FBS), 100 μg / ml penicillin, and 100 μg / ml streptomycin. The medium was then cultured at 37.0℃±0.5℃ and 5%±1.0% CO2. The medium was replaced in half every 2-3 days until the tissue pieces crawled out of the cells. 2) Shake, collect the lower layer of cells, wash with PBS, add 0.25% trypsin to digest for 2 min-3 min, add an equal volume of trypsin stop solution to stop digestion, gently pipette, centrifuge at 1200-1500 rpm / min for 5-8 min, and collect the cells.

39. The use of the pharmaceutical composition for preventing and treating facial nerve palsy in the recovery period as described in any one of claims 1-38 in the preparation of a medicament for preventing and treating facial nerve palsy in the recovery period.

40. The application as described in claim 39, wherein the pharmaceutical composition for preventing and treating facial nerve palsy in the recovery period is optionally used in combination with radiofrequency surgery, rehabilitation exercises, or a combination thereof.

41. The application as described in claim 40, wherein the radiofrequency surgery is performed at 41℃-42℃, 90V-140V, and 2Hz-6Hz, based on long-duration temperature-controlled high-voltage variable frequency pulse radiofrequency for 800-1400 seconds.

42. The application as described in claim 41, wherein the radiofrequency surgery is performed at 41℃-42℃, 100V-120V, and 3Hz-5Hz, based on a long-duration temperature-controlled high-voltage variable frequency pulse radiofrequency for 960-1200 seconds.

43. The application as described in claim 40, wherein the rehabilitation exercise is a facial paralysis rehabilitation exercise created by the inventor.

44. The application as described in claim 40, wherein the rehabilitation exercises are selected from any one or a combination of the first set of rehabilitation exercises and the second set of rehabilitation exercises.

45. The application as described in claim 44, wherein the first set of rehabilitation exercises includes: first, looking in a mirror; second, slowly closing the eyes, closing the eyes for 5 seconds, then opening the eyes and holding for 5 seconds, while controlling to prevent the corners of the mouth from lifting, correcting the associated movements; training the first set of rehabilitation exercises three times a day, with each set being trained 30 times.

46. ​​The application as described in claim 44, wherein the second set of rehabilitation exercises includes: first, looking in a mirror; second, opening the eyes and trying to keep the nerve branches silent; and third, pursing the lips, baring the teeth, and puffing out the cheeks around the mouth; and training the first set of rehabilitation exercises three times a day, with each set being trained 10 times.

47. The application as described in claim 39, wherein the treatment plan for preventing and treating facial nerve palsy in the recovery period includes pulsed radiofrequency surgery, postoperative oral medication and acupoint injection, and intraoperative and postoperative rehabilitation exercises.

48. The application as described in claim 39, wherein the facial nerve palsy is selected from any one or a combination of hemifacial spasm, facial paralysis / synkinesis, trigeminal neuralgia, glossopharyngeal neuralgia, facial neuritis, peripheral facial paralysis, and oculomotor spasm repair.

Images