CN117679519A - Pharmaceutical composition for preventing and treating acute facial paralysis and application thereof - Google Patents

Pharmaceutical composition for preventing and treating acute facial paralysis and application thereof Download PDF

Info

Publication number
CN117679519A
CN117679519A CN202311159238.4A CN202311159238A CN117679519A CN 117679519 A CN117679519 A CN 117679519A CN 202311159238 A CN202311159238 A CN 202311159238A CN 117679519 A CN117679519 A CN 117679519A
Authority
CN
China
Prior art keywords
pharmaceutical composition
acupoint
day
facial paralysis
time
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202311159238.4A
Other languages
Chinese (zh)
Inventor
陈琳
王宇
高文勇
李建军
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Beijing Darwin Cell Biotechnology Co ltd
Original Assignee
Beijing Darwin Cell Biotechnology Co ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Beijing Darwin Cell Biotechnology Co ltd filed Critical Beijing Darwin Cell Biotechnology Co ltd
Publication of CN117679519A publication Critical patent/CN117679519A/en
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61H—PHYSICAL THERAPY APPARATUS, e.g. DEVICES FOR LOCATING OR STIMULATING REFLEX POINTS IN THE BODY; ARTIFICIAL RESPIRATION; MASSAGE; BATHING DEVICES FOR SPECIAL THERAPEUTIC OR HYGIENIC PURPOSES OR SPECIFIC PARTS OF THE BODY
    • A61H39/00—Devices for locating or stimulating specific reflex points of the body for physical therapy, e.g. acupuncture
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/485—Morphinan derivatives, e.g. morphine, codeine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A61K31/51—Thiamines, e.g. vitamin B1
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7032—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a polyol, i.e. compounds having two or more free or esterified hydroxy groups, including the hydroxy group involved in the glycosidic linkage, e.g. monoglucosyldiacylglycerides, lactobionic acid, gangliosides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7135—Compounds containing heavy metals
    • A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/30—Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/16—Ginkgophyta, e.g. Ginkgoaceae (Ginkgo family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/40—Applying electric fields by inductive or capacitive coupling ; Applying radio-frequency signals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A63—SPORTS; GAMES; AMUSEMENTS
    • A63B—APPARATUS FOR PHYSICAL TRAINING, GYMNASTICS, SWIMMING, CLIMBING, OR FENCING; BALL GAMES; TRAINING EQUIPMENT
    • A63B23/00—Exercising apparatus specially adapted for particular parts of the body
    • A63B23/025—Exercising apparatus specially adapted for particular parts of the body for the head or the neck
    • A63B23/03—Exercising apparatus specially adapted for particular parts of the body for the head or the neck for face muscles

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Neurology (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pain & Pain Management (AREA)
  • Neurosurgery (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Medical Informatics (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Mycology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Botany (AREA)
  • Cell Biology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Rehabilitation Therapy (AREA)
  • Surgery (AREA)
  • Vascular Medicine (AREA)

Abstract

The invention relates to a pharmaceutical composition for preventing and treating acute facial paralysis, which contains any one or combination of dehydration drugs, antiviral drugs, anti-inflammatory drugs, nerve repair drugs and/or drugs for improving blood circulation. The pharmaceutical composition is beneficial to relieving the early facial paralysis edema, eliminating the inflammation of the facial paralysis part, nourishing the facial paralysis damaged nerve, repairing the damaged myelin sheath and axon, and has the advantages of remarkably improving the treatment efficiency, reducing or even avoiding the side effect, along with quick response, improving the cure rate, reducing the recurrence rate, reducing the dosage, relieving the treatment pain, shortening the treatment period, having no adverse reaction and the like.

Description

Pharmaceutical composition for preventing and treating acute facial paralysis and application thereof
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to a pharmaceutical composition for preventing and treating acute facial paralysis, a preparation method and application thereof.
Background
Facial nerve paralysis (also called facial neuritis, bell paralysis, facial rarefaction, facial distortion and the like) is a common facial nerve disease (accounting for 60% -75%) and is characterized by facial nerve edema and/or myelin edema in early pathological stage, facial nerve compression or local circulatory disturbance, axonal degeneration in late stage and most remarkable in the lactulum and facial nerve tube inner part. Facial paralysis is classified into an acute phase (within 15 days of onset), a convalescence phase (16 days to 6 months of onset) and a sequelae phase (more than 6 months of onset) according to the duration of onset of the patient.
Studies have shown that the incidence of facial paralysis is 11.5-53.3/10 ten thousand, the recurrence rate is 2.6% -15.2%, the patients are concentrated in men aged 20-40, their main clinical manifestations include facial autonomous movement, hypofunction or loss of expression, facial nerve and facial expression musculature dystrophy, etc., and influence the appearance, personal dignity and social image of the patients, serious ones even cause psychological disorders of the patients, depression anxiety, etc.
The treatment method of facial paralysis comprises the treatment of medicines (dehydration medicines or edema removal medicines, antiviral medicines, B vitamins, glucocorticoids, etc.), acupuncture, physiotherapy, facial rehabilitation training, etc. The treatment of mild and moderate patients for 2 weeks to 2 months obviously improves symptoms, the obvious efficiency and the clinical cure rate are 60% -70%, but more than 30% of moderate and severe patients have sequelae. To date, no specific drug has been used to treat acute phase facial paralysis. For this reason, there is a need to develop a pharmaceutical composition for safely and effectively treating acute phase facial paralysis.
Patent applications (CN 2023100429139, PCT/CN2023/073566, CN2023100429143, PCT/CN 2023/073582) disclose technical content about a neural repair protein extract and a neural repair protein composition having repair efficacy, which are essential technical references and components of the present application.
Disclosure of Invention
The invention aims to provide a pharmaceutical composition for preventing and treating acute facial paralysis, which contains any one or combination of dehydration drugs, antiviral drugs, anti-inflammatory drugs, nerve repair drugs and/or drugs for improving blood circulation.
In a preferred embodiment of the present invention, the dehydration-based drug is selected from any one of mannitol, sorbitol, aescin sodium, 50% hypertonic glucose solution, or a combination thereof.
In a preferred embodiment of the present invention, the antiviral drug is selected from any one or combination of acyclovir, valacyclovir, dibazol, rhinoceros detoxification, virucide, fampicvir (faviravir), paxlovid, mo Nuola (Molnupiravir), oseltamivir, lei Midi vitamin, rendimivir (Remdesivir, GS-5734), indinavir, saquinavir, lopinavir, ritonavir (Ritonavir), atazanavir, darunavir, telanavir, fosamprenavir, enzaton Weipu ritodunder, abacavir, eticonvir, ma Liba, raltegafvir, ribavirin, rimantadine, oseltamivir, zanavir, peramivir, ganciclovir, baloflavir Sha Wei (baenavir), and fevernivir.
In a preferred embodiment of the present invention, the anti-inflammatory drug is selected from any one of dexamethasone, methylprednisolone, prednisone, methylprednisolone (methylprednisolone), cortisone, hydrocortisone, prednisone, prednisolone, or a combination thereof.
In a preferred embodiment of the present invention, the nerve repair drug and/or the blood circulation improving drug is selected from any one or a combination of murine nerve growth factor, monosialoganglioside (GM 1), cerebroside carnosine, mecobalamin, adenosyl cobalamin, compound vitamin B, butylphthalide, cinepazide maleate, edaravone dexkaempferol, citicoline, sodium citicoline, ganglioside, oxiracetam, piracetam, aniracetam, nerve growth factor, citicoline, neurotoxicam, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin E, compound brain peptide ganglioside, brain protein, and nervonic acid.
In a preferred technical scheme of the invention, the pharmaceutical composition for preventing and treating acute phase facial paralysis contains any one or combination of mannitol, sodium aescinate, acyclovir or valacyclovir, dexamethasone, prednisone, citicoline sodium, ginkgo leaf, murine nerve growth factor, mecobalamin and adenosylcobalamin.
In a preferred technical scheme of the invention, the pharmaceutical composition for preventing and treating acute phase facial paralysis consists of a pharmaceutical composition for single oral administration and a pharmaceutical composition for single acupoint injection.
In the preferred technical scheme of the invention, the pharmaceutical composition for single oral administration contains 125-250ml of mannitol, 0.5mg of mecobalamin, 5mg of anti-inflammatory drugs, 30mg of fasudil, 30ug of murine nerve growth factor and 15ml of ginkgo leaf extract, wherein the anti-inflammatory drugs are selected from any one or combination of dexamethasone, sodium aescinate and methylprednisolone.
In a preferred embodiment of the present invention, the oral pharmaceutical composition is administered according to the following schedule:
(1) Intravenous injection of dehydrating agent mannitol 125-250ml for 2 times/day;
(2) Intramuscular injection of 0.5mg mecobalamin 1 time every 1 day;
(3) Intravenous injection of 5mg of dexamethasone, 2 times/day;
(4) Fasudil is injected intravenously, 30 mg/time, 2 times/day;
(5) Intramuscular injection of mouse nerve growth factor 30 ug/time, 1 time/day;
(6) The ginkgo leaf extract is injected intravenously 15 ml/time, 1 time/day.
In the preferred technical scheme of the invention, the pharmaceutical composition for single oral administration contains 125-250ml of mannitol, 10-20mg of aescin sodium, 0.3-0.4g of acyclovir or valaciclovir, 1-5mg of dexamethasone or prednisone tablet, 0.2-0.5mg of citicoline sodium tablet, 0.1-0.2g of ginkgo leaf, 30-90ug of murine nerve growth factor, 0.5-1.0mg of mecobalamin, 0.1-0.5mg of adenosylcobalamine and 2-5mg of dexamethasone or any one or combination thereof.
In a preferred embodiment of the present invention, the oral pharmaceutical composition is administered according to the following schedule:
(1) Intravenous mannitol (125-250 ml/time, 1-2 times/day) and aescin sodium (20 mg/time, 1-2 times/day) for 7-14 days;
(2) Intravenous acyclovir or valacyclovir 0.3 g/time, 2 times/day for 7-14 days;
(3) Dexamethasone is injected intravenously (5-10 mg/day, 7-10 days of administration);
(4) Oral citicoline sodium tablet (0.2 g/time, 3 times/day, administration for 2-3 weeks) and ginkgo leaf (0.1-
0.2 g/time, 3 times/day, 2 weeks of administration);
(5) After oral administration of prednisone acetate tablet (5 mg/time, 2 times/day for one week), prednisone acetate tablet (5 mg/time, 1 time/day for one week);
in a preferred embodiment of the present invention, the pharmaceutical composition for oral administration is selected from any one of simultaneous administration and sequential administration or a combination thereof.
In the preferred technical scheme of the invention, the single acupoint injection pharmaceutical composition consists of the mouse nerve growth factor, the mecobalamin and the vitamin B1 according to the mass ratio of 0.03:0.5:200, and preferably, the mouse nerve growth factor 30ug, the mecobalamin 0.5mg and the vitamin B1 200mg are prepared into 5ml of liquid medicine and then the liquid medicine is injected into the acupoint.
In the preferred technical scheme of the invention, the pharmaceutical composition for single acupoint injection contains 30ug of mouse nerve growth factor, 0.5mg of mecobalamin and vitamin B 1 200mg, or any combination thereof.
In the preferred technical scheme of the invention, the single acupoint injection pharmaceutical composition consists of 30-90ug of mouse nerve growth factor, 0.5-1.0mg of mecobalamin, 0.1-0.5mg of adenosylcobalamin and 2-5mg of dexamethasone.
In a preferred technical scheme of the invention, the single acupoint injection pharmaceutical composition consists of 30ug of mouse nerve growth factor, 0.5mg of mecobalamin, 0.5mg of adenosylcobalamin, 2mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of the lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.
In a preferred technical scheme of the invention, the single acupoint injection pharmaceutical composition consists of 30ug of mouse nerve growth factor, 0.5mg of mecobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of the lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.
In a preferred technical scheme of the invention, the single acupoint injection pharmaceutical composition consists of 90ug of mouse nerve growth factor, 1.0mg of mecobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of the lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.
In a preferred technical scheme of the invention, the single acupoint injection pharmaceutical composition consists of 60ug of mouse nerve growth factor, 0.8mg of mecobalamin, 0.5mg of adenosylcobalamin, 3mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of the lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.
In a preferred embodiment of the present invention, the pharmaceutical composition for single acupoint injection optionally contains 100-300mg of any one or combination of a neural repair cell protein extract and/or a neural repair protein composition having a repair effect.
In the preferred technical scheme of the invention, the pharmaceutical composition for single acupoint injection is clinically matched.
In the preferred technical scheme of the invention, the yang white acupoint, the temple, the Sibai acupoint, the Yingxiang acupoint, the Juliao acupoint, the Dicang acupoint and the Jiache acupoint of the affected side face part are selected for acupoint injection.
In the preferred technical scheme of the invention, the medicine composition for single acupoint injection is injected once per acupoint every day, and 7 days is a treatment course.
In the preferred technical scheme of the invention, each acupoint injection treatment is carried out for 2-6 treatment courses, preferably 4-5 treatment courses.
Another object of the present invention is to provide an application of the pharmaceutical composition in preparing a medicament for preventing and treating acute phase facial paralysis, wherein the pharmaceutical composition for preventing and treating acute phase facial paralysis contains any one or a combination of dehydration-type medicament, antiviral medicament, anti-inflammatory medicament, nerve repair medicament and/or medicament for improving blood circulation.
In a preferred embodiment of the present invention, the dehydration-based drug is selected from any one of mannitol, sorbitol, aescin sodium, 50% hypertonic glucose solution, or a combination thereof.
In a preferred embodiment of the present invention, the antiviral drug is selected from any one or combination of acyclovir, valacyclovir, dibazol, rhinoceros detoxification, virucide, fampicvir (faviravir), paxlovid, mo Nuola (Molnupiravir), oseltamivir, lei Midi vitamin, rendimivir (Remdesivir, GS-5734), indinavir, saquinavir, lopinavir, ritonavir (Ritonavir), atazanavir, darunavir, telanavir, fosamprenavir, enzaton Weipu ritodunder, abacavir, eticonvir, ma Liba, raltegafvir, ribavirin, rimantadine, oseltamivir, zanavir, peramivir, ganciclovir, baloflavir Sha Wei (baenavir), and fevernivir.
In a preferred embodiment of the present invention, the anti-inflammatory drug is selected from any one of dexamethasone, methylprednisolone, prednisone, methylprednisolone (methylprednisolone), cortisone, hydrocortisone, prednisone, prednisolone, or a combination thereof.
In a preferred embodiment of the present invention, the nerve repair drug and/or the blood circulation improving drug is selected from any one or a combination of murine nerve growth factor, monosialoganglioside (GM 1), cerebroside carnosine, mecobalamin, adenosyl cobalamin, compound vitamin B, butylphthalide, cinepazide maleate, edaravone dexkaempferol, citicoline, sodium citicoline, ganglioside, oxiracetam, piracetam, aniracetam, nerve growth factor, citicoline, neurotoxicam, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin E, compound brain peptide ganglioside, brain protein, and nervonic acid.
In a preferred technical scheme of the invention, the pharmaceutical composition for preventing and treating acute phase facial paralysis contains any one or combination of mannitol, sodium aescinate, acyclovir or valacyclovir, dexamethasone, prednisone, citicoline sodium, ginkgo leaf, murine nerve growth factor, mecobalamin and adenosylcobalamin.
In a preferred technical scheme of the invention, the pharmaceutical composition for preventing and treating acute phase facial paralysis consists of a pharmaceutical composition for single oral administration and a pharmaceutical composition for single acupoint injection.
In the preferred technical scheme of the invention, the pharmaceutical composition for single oral administration contains 125-250ml of mannitol, 0.5mg of mecobalamin, 5mg of anti-inflammatory drugs, 30mg of fasudil, 30ug of murine nerve growth factor and 15ml of ginkgo leaf extract, wherein the anti-inflammatory drugs are selected from any one or combination of dexamethasone, sodium aescinate and methylprednisolone.
In a preferred embodiment of the present invention, the oral pharmaceutical composition is administered according to the following schedule:
(1) Intravenous injection of dehydrating agent mannitol 125-250ml for 2 times/day;
(2) Intramuscular injection of 0.5mg mecobalamin 1 time every 1 day;
(3) Intravenous injection of 5mg of dexamethasone, 2 times/day;
(4) Fasudil is injected intravenously, 30 mg/time, 2 times/day;
(5) Intramuscular injection of mouse nerve growth factor 30 ug/time, 1 time/day;
(6) The ginkgo leaf extract is injected intravenously 15 ml/time, 1 time/day.
In the preferred technical scheme of the invention, the pharmaceutical composition for single oral administration contains 125-250ml of mannitol, 10-20mg of aescin sodium, 0.3-0.4g of acyclovir or valaciclovir, 1-5mg of dexamethasone or prednisone tablet, 0.2-0.5mg of citicoline sodium tablet, 0.1-0.2g of ginkgo leaf, 30-90ug of murine nerve growth factor, 0.5-1.0mg of mecobalamin, 0.1-0.5mg of adenosylcobalamine and 2-5mg of dexamethasone or any one or combination thereof.
In a preferred embodiment of the present invention, the oral pharmaceutical composition is administered according to the following schedule:
(1) Intravenous mannitol (125-250 ml/time, 1-2 times/day) and aescin sodium (20 mg/time, 1-2 times/day) for 7-14 days;
(2) Intravenous acyclovir or valacyclovir 0.3 g/time, 2 times/day for 7-14 days;
(3) Dexamethasone is injected intravenously (5-10 mg/day, 7-10 days of administration);
(4) Oral citicoline sodium tablet (0.2 g/time, 3 times/day, administration for 2-3 weeks) and ginkgo leaf (0.1-
0.2 g/time, 3 times/day, 2 weeks of administration);
(5) After oral administration of prednisone acetate tablet (5 mg/time, 2 times/day for one week), prednisone acetate tablet (5 mg/time, 1 time/day for one week);
in a preferred embodiment of the present invention, the pharmaceutical composition for oral administration is selected from any one of simultaneous administration and sequential administration or a combination thereof.
In the preferred technical scheme of the invention, the single acupoint injection pharmaceutical composition consists of the mouse nerve growth factor, the mecobalamin and the vitamin B1 according to the mass ratio of 0.03:0.5:200, and preferably, the mouse nerve growth factor 30ug, the mecobalamin 0.5mg and the vitamin B1 200mg are prepared into 5ml of liquid medicine and then the liquid medicine is injected into the acupoint.
In the preferred technical scheme of the invention, the pharmaceutical composition for single acupoint injection contains 30ug of mouse nerve growth factor, 0.5mg of mecobalamin and vitamin B 1 200mg, or any combination thereof.
In the preferred technical scheme of the invention, the single acupoint injection pharmaceutical composition consists of 30-90ug of mouse nerve growth factor, 0.5-1.0mg of mecobalamin, 0.1-0.5mg of adenosylcobalamin and 2-5mg of dexamethasone.
In a preferred technical scheme of the invention, the single acupoint injection pharmaceutical composition consists of 30ug of mouse nerve growth factor, 0.5mg of mecobalamin, 0.5mg of adenosylcobalamin, 2mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of the lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.
In a preferred technical scheme of the invention, the single acupoint injection pharmaceutical composition consists of 30ug of mouse nerve growth factor, 0.5mg of mecobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of the lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.
In a preferred technical scheme of the invention, the single acupoint injection pharmaceutical composition consists of 90ug of mouse nerve growth factor, 1.0mg of mecobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of the lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.
In a preferred technical scheme of the invention, the single acupoint injection pharmaceutical composition consists of 60ug of mouse nerve growth factor, 0.8mg of mecobalamin, 0.5mg of adenosylcobalamin, 3mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of the lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.
In a preferred embodiment of the present invention, the pharmaceutical composition for single acupoint injection optionally contains 100-300mg of any one or combination of a neural repair cell protein extract and/or a neural repair protein composition having a repair effect.
In the preferred technical scheme of the invention, the pharmaceutical composition for single acupoint injection is clinically matched.
In the preferred technical scheme of the invention, the yang white acupoint, the temple, the Sibai acupoint, the Yingxiang acupoint, the Juliao acupoint, the Dicang acupoint and the Jiache acupoint of the affected side face part are selected for acupoint injection.
In the preferred technical scheme of the invention, the medicine composition for single acupoint injection is injected once per acupoint every day, and 7 days is a treatment course.
In the preferred technical scheme of the invention, each acupoint injection treatment is carried out for 2-6 treatment courses, preferably 4-5 treatment courses.
It is another object of the present invention to provide a therapeutic regimen for treating acute phase facial paralysis, which comprises using the pharmaceutical composition for preventing and treating acute phase facial paralysis of the present invention, which contains any one or a combination of a dehydration-type drug, an antiviral drug, an anti-inflammatory drug, a nerve repair drug, and/or a blood circulation improving drug.
In a preferred embodiment of the present invention, the dehydration-based drug is selected from any one of mannitol, sorbitol, aescin sodium, 50% hypertonic glucose solution, or a combination thereof.
In a preferred embodiment of the present invention, the antiviral drug is selected from any one or combination of acyclovir, valacyclovir, dibazol, rhinoceros detoxification, virucide, fampicvir (favipiravir), paxlovid, mo Nuola (molnuiravir), oseltamivir, lei Midi vitamin, rendimivir (Remdesivir, GS-5734), indinavir, saquinavir, lopinavir, ritonavir (Ritonavir), atazanavir, darunavir, telanavir, fosamprenavir, enzaton Weipu ritodunder, abacavir, eticonvir, ma Liba, raltegafvir, ribavirin, rimantadine, oseltamivir, zanavir, zanamivir, peramivir, ganciclovir, baloflavir Sha Wei (baenavir), and feverine.
In a preferred embodiment of the present invention, the anti-inflammatory drug is selected from any one of dexamethasone, methylprednisolone, prednisone, methylprednisolone (methylprednisolone), cortisone, hydrocortisone, prednisone, prednisolone, or a combination thereof.
In a preferred embodiment of the present invention, the nerve repair drug and/or the blood circulation improving drug is selected from any one or a combination of murine nerve growth factor, monosialoganglioside (GM 1), cerebroside carnosine, mecobalamin, adenosyl cobalamin, compound vitamin B, butylphthalide, cinepazide maleate, edaravone dexkaempferol, citicoline, sodium citicoline, ganglioside, oxiracetam, piracetam, aniracetam, nerve growth factor, citicoline, neurotoxicam, oryzanol, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin E, compound brain peptide ganglioside, brain protein, and nervonic acid.
In a preferred technical scheme of the invention, the pharmaceutical composition for preventing and treating acute phase facial paralysis contains any one or combination of mannitol, sodium aescinate, acyclovir or valacyclovir, dexamethasone, prednisone, citicoline sodium, ginkgo leaf, murine nerve growth factor, mecobalamin and adenosylcobalamin.
In a preferred technical scheme of the invention, the pharmaceutical composition for preventing and treating acute phase facial paralysis consists of a pharmaceutical composition for single oral administration and a pharmaceutical composition for single acupoint injection.
In the preferred technical scheme of the invention, the pharmaceutical composition for single oral administration contains 125-250ml of mannitol, 0.5mg of mecobalamin, 5mg of anti-inflammatory drugs, 30mg of fasudil, 30ug of murine nerve growth factor and 15ml of ginkgo leaf extract, wherein the anti-inflammatory drugs are selected from any one or combination of dexamethasone, sodium aescinate and methylprednisolone.
In a preferred embodiment of the present invention, the oral pharmaceutical composition is administered according to the following schedule:
(1) Intravenous injection of dehydrating agent mannitol 125-250ml for 2 times/day;
(2) Intramuscular injection of 0.5mg mecobalamin 1 time every 1 day;
(3) Intravenous injection of 5mg of dexamethasone, 2 times/day;
(4) Fasudil is injected intravenously, 30 mg/time, 2 times/day;
(5) Intramuscular injection of mouse nerve growth factor 30 ug/time, 1 time/day;
(6) The ginkgo leaf extract is injected intravenously 15 ml/time, 1 time/day.
In the preferred technical scheme of the invention, the pharmaceutical composition for single oral administration contains 125-250ml of mannitol, 10-20mg of aescin sodium, 0.3-0.4g of acyclovir or valaciclovir, 1-5mg of dexamethasone or prednisone tablet, 0.2-0.5mg of citicoline sodium tablet, 0.1-0.2g of ginkgo leaf, 30-90ug of murine nerve growth factor, 0.5-1.0mg of mecobalamin, 0.1-0.5mg of adenosylcobalamine and 2-5mg of dexamethasone or any one or combination thereof.
In a preferred embodiment of the present invention, the oral pharmaceutical composition is administered according to the following schedule:
(1) Intravenous mannitol (125-250 ml/time, 1-2 times/day) and aescin sodium (20 mg/time, 1-2 times/day) for 7-14 days;
(2) Intravenous acyclovir or valacyclovir 0.3 g/time, 2 times/day for 7-14 days;
(3) Dexamethasone is injected intravenously (5-10 mg/day, 7-10 days of administration);
(4) Oral citicoline sodium tablet (0.2 g/time, 3 times/day, administration for 2-3 weeks) and ginkgo leaf (0.1-
0.2 g/time, 3 times/day, 2 weeks of administration);
(5) After oral administration of prednisone acetate tablet (5 mg/time, 2 times/day for one week), prednisone acetate tablet (5 mg/time, 1 time/day for one week);
in a preferred embodiment of the present invention, the pharmaceutical composition for oral administration is selected from any one of simultaneous administration and sequential administration or a combination thereof.
In the preferred technical scheme of the invention, the single acupoint injection pharmaceutical composition consists of the mouse nerve growth factor, the mecobalamin and the vitamin B1 according to the mass ratio of 0.03:0.5:200, and preferably, the mouse nerve growth factor 30ug, the mecobalamin 0.5mg and the vitamin B1 200mg are prepared into 5ml of liquid medicine and then the liquid medicine is injected into the acupoint.
In the preferred technical scheme of the invention, the single acupoint injection is used The pharmaceutical composition of (2) contains 30ug of mouse nerve growth factor, 0.5mg of mecobalamin and vitamin B 1 200mg, or any combination thereof.
In the preferred technical scheme of the invention, the single acupoint injection pharmaceutical composition consists of 30-90ug of mouse nerve growth factor, 0.5-1.0mg of mecobalamin, 0.1-0.5mg of adenosylcobalamin and 2-5mg of dexamethasone.
In a preferred technical scheme of the invention, the single acupoint injection pharmaceutical composition consists of 30ug of mouse nerve growth factor, 0.5mg of mecobalamin, 0.5mg of adenosylcobalamin, 2mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of the lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.
In a preferred technical scheme of the invention, the single acupoint injection pharmaceutical composition consists of 30ug of mouse nerve growth factor, 0.5mg of mecobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of the lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.
In a preferred technical scheme of the invention, the single acupoint injection pharmaceutical composition consists of 90ug of mouse nerve growth factor, 1.0mg of mecobalamin, 0.5mg of adenosylcobalamin, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of the lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.
In a preferred technical scheme of the invention, the single acupoint injection pharmaceutical composition consists of 60ug of mouse nerve growth factor, 0.8mg of mecobalamin, 0.5mg of adenosylcobalamin, 3mg of dexamethasone and 1ml of lidocaine hydrochloride, wherein the concentration of the lidocaine hydrochloride is selected from any one of 0.8%, 1%, 1.5% and 2%.
In a preferred embodiment of the present invention, the pharmaceutical composition for single acupoint injection optionally contains 100-300mg of any one or combination of a neural repair cell protein extract and/or a neural repair protein composition having a repair effect.
In the preferred technical scheme of the invention, the pharmaceutical composition for single acupoint injection is clinically matched.
In the preferred technical scheme of the invention, the yang white acupoint, the temple, the Sibai acupoint, the Yingxiang acupoint, the Juliao acupoint, the Dicang acupoint and the Jiache acupoint of the affected side face part are selected for acupoint injection.
In the preferred technical scheme of the invention, the medicine composition for single acupoint injection is injected once per acupoint every day, and 7 days is a treatment course.
In the preferred technical scheme of the invention, each acupoint injection treatment is carried out for 2-6 treatment courses, preferably 4-5 treatment courses.
For clarity of presentation of the present invention, the neural repair cell protein extract or neural repair cell protein composition with repair efficacy according to the present invention was prepared with reference to patent applications (CN 2023100429139, PCT/CN2023/073566, CN2023100429143, PCT/CN 2023/073582).
In a preferred technical scheme of the invention, the preparation method of the nerve repair cell protein extract with the nerve repair effect comprises the following steps:
s-1 the density was set at 5.0X10 6 personal/mL-5.0X10 7 The mesenchymal stem cells of each/mL are placed in a culture medium containing DMEM/F12-50%, RPMI 1640 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 (18 AA) 0.01-0.1% and 2-10 mu mol L/L stressor, and then placed in a medium at 37.0 ℃ plus or minus 0.5 ℃ and 5% plusor minus 1.0% CO 2 After 2h-6h of culture under the condition, separating, washing and collecting cells, wherein the stressor is selected from any one of compounds 1-16 or a combination thereof;
s-2: the cells were collected at a density of 5.0×10 6 personal/mL-5.0X10 7 Dispersing the cells/mL in a solvent, and then carrying out ultrasonic treatment at the temperature of 2-8 ℃ to prepare a cell lysate, wherein 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, separating the cell lysate prepared in the step S-2, and filtering the obtained separating liquid with 0.45um and 0.22um filter membranes in sequence to obtain the cell lysate.
In the preferred technical scheme of the invention, the culture medium in the step S-1 contains stress substances of DMEM/F12-45%, RPMI1640 42-45%, bovine Serum Albumin (BSA) 0.5-1.5%, epidermal Growth Factor (EGF) 5-10ug/mL, fibroblast Growth Factor (FGF) 5-10ug/mL, insulin transferrin 5-10ug/mL, compound amino acid (18 AA) 0.02-0.05% and 3-8 mu mol/L.
In a preferred technical scheme of the invention, the culture medium in the step S-1 contains DMEM/F12, RPMI1640 45, bovine Serum Albumin (BSA) 0.5, epidermal Growth Factor (EGF) 10ug/mL, fibroblast Growth Factor (FGF) 10ug/mL, insulin transferrin 10ug/mL, compound amino acid (18 AA) 0.05% and stressors of 4-6 mu mol/L.
In a preferred embodiment of the present invention, the mesenchymal stem cells of step S-1 have a density of 8.0X10 6 -2.0×10 7 Each mL is preferably 8.0X10 6 -1.0×10 7 And each mL.
In a preferred embodiment of the invention, the mesenchymal stem cells of step S-1 are cultured in the medium for 3h to 5h, preferably 3.5h to 4.5h.
In a preferred embodiment of the present invention, the solvent used for washing the cells in step S-1 is selected from any one or a combination of physiological saline, 5% dextrose solution, phosphate Buffer (PBS), TBPS buffer, TBST buffer, tris buffer, and the like, and the number of times of washing the cells is 2 to 5 times, preferably 3 to 4 times.
In a preferred embodiment of the present invention, the separation in step S-1 is selected from any one of centrifugation and filtration or a combination thereof, wherein the centrifugation conditions are 1000-2000rpm for 3-15min, preferably 1200-1500 rpm for 5-10min.
In the preferred technical scheme of the invention, the ultrasonic conditions of the step S-2 are as follows: working for 3s at 2-8 ℃ under the conditions of 25kHZ and 360W and then spacing for 1s, and carrying out ultrasonic treatment for 1-5min.
In a preferred embodiment of the present invention, the separation in step S-3 is selected from any one or a combination of centrifugation at 2000-8000rpm for 10-30min, multistage centrifugation, multistage filtration, preferably 3000-7000rpm for 15-25min.
In a preferred embodiment of the present invention, the multistage centrifugation in step S-3 is carried out sequentially at 3000-4000rpm for 3-5min, at 5000-6000rpm for 3-5min, and at 7000rpm for 5-8min.
In a preferred technical scheme of the invention, the pore diameter of the multi-stage filtration membrane is selected from any one of 80um, 50um, 30um, 10um and 5 um.
In a preferred embodiment of the present invention, the cellular protein extract obtained in step S-3 is frozen, preferably at-40℃to-20 ℃.
In the preferred technical scheme of the invention, the cellular protein extract prepared in the step S-3 is subjected to enzymolysis by adopting any one of nuclease or totipotent nuclease and then is subjected to separation and purification.
In a preferred embodiment of the present invention, the mesenchymal stem cells are cultured or primary mesenchymal stem cells are cultured by a method of culturing in the art.
In a preferred embodiment of the present invention, the culture of the mesenchymal stem cells comprises the following steps: the primary mesenchymal stem cells are prepared according to the initial density of 5.0x10 5 -5.0×10 6 Adding the mixture/ml into a subculture medium, and placing the subculture medium at 37.0deg.C+ -0.5deg.C and 5% + -1.0% CO 2 Culturing under the condition for 10-15 days, observing yellowing of the subculture medium every 2-3 days, and half-changing the subculture medium, wherein the subculture medium contains 10% FBS, 100U/ml penicillin and 100ug/ml streptomycin DMEM/F12 medium.
In a preferred embodiment of the present invention, the culture of primary mesenchymal stem cells comprises the steps of:
1) Cleaning umbilical cord, sterilizing, dissecting tissue, collecting the tissue of HUALONG gel layer, cutting into 3mm pieces 3 Is used for the production of the small blocks,centrifuging, washing, collecting tissue blocks, placing in DMEM/F12 medium containing 10% fetal bovine serum FBS, 100ug/ml penicillin, 100ug/ml streptomycin, and placing at 37.0deg.C+ -0.5deg.C, 5% + -1.0% CO 2 Culturing under the condition that the culture medium is half replaced every 2-3 days, and culturing until the tissue blocks climb out of the cells;
2) Shaking, collecting low-layer cells, washing with PBS, adding 0.25% trypsin, digesting for 2min-3min, adding equal volume of trypsin stopping solution, stopping digestion, gently blowing with a sucker, centrifuging at 1200-1500rpm/min for 5-8min, and collecting cells.
Unless otherwise indicated, when the invention relates to a percentage between liquids, the percentages are volume/volume percentages; the invention relates to the percentage between liquid and solid, said percentage being volume/weight percentage; the invention relates to the percentage between solids and liquids, the percentage being weight/volume percentage; the balance being weight/weight percent.
The invention was evaluated, unless otherwise indicated, using the following method:
1. the invention positions and takes acupoints according to acupoints specified by national standards of the people's republic of China (GB/T12345-2006) issued by the national technical supervision agency.
2. Clinical scores were assessed using the House-Brakmann facial nerve function stratification efficacy assessment table.
Compared with the prior art, the invention has the following beneficial effects:
1. the invention scientifically combines medicines on the market for treating acute facial paralysis, adopts simultaneous administration and/or sequential administration modes for treating the affected side, is beneficial to relieving the edema of the facial paralysis at early stage, eliminating the inflammation of the facial paralysis part, nourishing the facial paralysis to damage nerves and repairing damaged myelin and axons. The dehydration medicine in the pharmaceutical composition is used for eliminating the acute facial paralysis oedema, reducing or even eliminating facial nerve injury caused by the acute oedema, and is beneficial to the treatment, recovery and prognosis of the acute facial paralysis; the antiviral drug is used for resisting viruses, eliminating the etiology of the facial paralysis, and is beneficial to the treatment, recovery and prognosis of the acute facial paralysis; the anti-inflammatory medicament is used for clearing facial paralysis inflammatory factors, is beneficial to clearing facial paralysis inflammation and edema, and is beneficial to treatment, rehabilitation and prognosis of acute facial paralysis; the nerve repairing medicine and/or the medicine for improving blood circulation is used for improving blood circulation disorder caused by facial paralysis edema, viruses, inflammation and the like, repairing facial nerve injury caused by facial paralysis edema, viruses, inflammation and the like, and is beneficial to treatment, rehabilitation and prognosis of acute facial paralysis.
2. The invention adopts any one or combination of acupuncture point injection targeting positioning administration nerve repairing medicine, blood circulation improving medicine, neurotrophic medicine, anti-inflammatory medicine and antiviral medicine, realizes accurate treatment and scientific treatment by using acupuncture points, improves curative effect, reduces sequelae occurrence rate, reduces medication dosage, reduces facial disability rate, obviously improves treatment efficiency and reduces or even avoids side effect, and has the advantages of quick effect, improvement of cure rate, reduction of recurrence rate, reduction of treatment pain, shortening of treatment period, no adverse reaction and the like, and reduces economic burden.
Detailed Description
The following detailed description of the invention is provided in connection with specific embodiments, but is not intended to limit the scope of the invention.
Example 1Preparation of neural repair cell protein extract with repair effect
1. Culture of primary mesenchymal Stem cells
The culture of primary mesenchymal stem cells comprises the following steps:
1) Cleaning umbilical cord, sterilizing, dissecting tissue, collecting the tissue of HUALONG gel layer, cutting into 3mm pieces 3 Is centrifuged, washed, tissue pieces are collected, placed in a culture flask, DMEM/F12 medium containing 10% fetal bovine serum FBS, 100ug/ml penicillin, 100ug/ml streptomycin is added, and then placed at 37 ℃ and 5% CO 2 Culturing under the condition to promote the adherence of the culture medium, observing the yellowing of the culture medium every 2-3 days, and half-changing the culture medium, and culturing for 10-12 days until the cells on the tissue block edge can climb out;
2) Slightly shaking to drop the tissue blocks, and respectively collecting the tissue blocks and lower cells, wherein the collected tissue blocks are subjected to wall-attached culture;
3) Washing the collected low-layer cells with PBS, adding a proper amount of 0.25% trypsin for digestion for 2-3 min, adding an equal volume of trypsin stopping solution for stopping digestion, lightly blowing a bottle bottom by a suction tube, centrifuging at 1500rpm for 5min, and collecting the cells.
2. Subculture of Primary mesenchymal Stem cells (culture of mesenchymal Stem cells)
Subculture of primary mesenchymal stem cells (culture of mesenchymal passage stem cells): the primary mesenchymal stem cells are prepared according to the initial density of 5.0x10 5 -5.0×10 6 Each ml was added to DMEM/F12 medium containing 10% FBS, 100U/ml penicillin and 100ug/ml streptomycin, and then placed at 37.0deg.C.+ -. 0.5 ℃ and 5%.+ -. 1% CO 2 Culturing under the condition for 10-15 days at intervals of 2-3 days, and half-changing the culture medium after observing the yellowing of the culture medium.
3. Preparation of Compounds 1-16 reference 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).
The preparation method of the nerve repair cell protein extract with the nerve repair effect comprises the following steps:
(1) Mesenchymal passaged cells were passaged at a density of 8.0X10 6 Adding into culture medium containing DMEM/F1245%, RPMI1640 45%, bovine Serum Albumin (BSA) 0.5%, epidermal Growth Factor (EGF) 10ug/mL, fibroblast Growth Factor (FGF) 10ug/mL, insulin transferrin 10ug/mL, compound amino acid (18 AA) 0.05% and 5 μmol/L of compound 16, and placing at 37deg.C and 5% CO 2 After 4h incubation, cells were collected after centrifugation at 1200rpm for 5min and washing 3 times with PBS;
(2) The cells collected in step (1) were packed at a density of 1.0X10 7 Dispersing the cells/mL in physiological saline, and performing ultrasonic treatment at 2-8deg.C, 25kHz and 360W for 3s and 1s gap for 2min to obtain cell lysate;
(3) Centrifuging the cell lysate prepared in the step (2) at 7000rpm for 20min, and filtering the obtained centrifugate sequentially with 0.45um and 0.22um filter membrane to obtain cell protein extract;
(4) And (3) adding the required amount of mannitol into the cellular protein extract prepared in the step (3), stirring, uniformly mixing, and freeze-drying, wherein the obtained freeze-dried preparation contains 5% mannitol (m/m).
Test example 1The pharmaceutical composition is used for researching the treatment effect of acute facial paralysis
60 patients in the acute phase were selected and divided into 1 group (10), 2 groups (40) and 3 groups (10). Patient inclusion criteria: the traditional Chinese medicine and western medicine diagnosis standards of facial neuritis are met, patients are unilateral acute morbidity, and obvious symptoms appear in a few hours or 1-3 days; 20-70 years old; within 15 days of onset; the H-B is classified above the II level; informed consent was received for this trial; has good compliance, and no sequelae, and is suitable for unconscious patients and patients with facial paralysis after the first onset or past onset. Contraindications: those with complete fracture or loss of facial nerves; injection site infected or skin injured person; pregnant or lactating women, may affect the health of the fetus or infant; allergic reactions or other adverse reactions may be caused to the drug allergic person; mental disorders or those who cannot be treated with rehabilitation or corrective training.
The treatment regimen of group 1 (7 days per treatment course, 4 treatment courses) included oral administration and point injection administration.
1. Regimen of simultaneous and/or sequential administration of post-operative oral medications:
1) Intravenous injection of dehydrating agent mannitol 125-250ml for 2 times/day;
2) Intramuscular injection of 0.5mg mecobalamin 1 time every 1 day;
3) Intravenous injection of 5mg of dexamethasone, 2 times/day;
4) Fasudil is injected intravenously, 30 mg/time, 2 times/day;
5) Intramuscular injection of mouse nerve growth factor 30 ug/time, 1 time/day;
6) Intravenous injection of ginkgo leaf extract 15 ml/time, 1 time/day;
2. acupoint injection dosing scheme:
the single acupoint injection pharmaceutical composition comprises 30ug of mouse nerve growth factor, 0.5mg of mecobalamin and 200mg of vitamin B1, is prepared into 5ml of liquid medicine, and is prepared for temporary use, and is prepared by selecting YANGBAI acupoint, taiyang acupoint, siBAI acupoint, yingxiang acupoint, juliao acupoint, dicang acupoint and Jiache acupoint of the affected side for acupoint injection for 1 time per day.
The treatment regimen of group 2 (7 days per treatment course, 4 treatment courses) included oral administration and point injection administration.
1. Regimen of simultaneous and/or sequential administration of oral drugs:
(1) Mannitol (125 ml/time, 2 times/day) and sodium aescinate (20 mg/time, 2 times/day) were administered intravenously for 14 days;
(2) Valacyclovir is administered intravenously at 0.3 g/dose, 2 times/day for 14 days;
(3) Dexamethasone is injected intravenously for 10 mg/day, and the dosage is 10 days;
(4) Oral citicoline sodium tablet (0.2 g/time, 3 times/day, 2-3 weeks of administration) and ginkgo leaf tablet (0.1 g/time, 3 times/day, 2 weeks of administration);
(5) After oral administration of prednisone acetate tablet (5 mg/time, 2 times/day for one week), prednisone acetate tablet (5 mg/time, 1 time/day for one week);
2. acupoint injection dosing scheme:
the single acupoint injection pharmaceutical composition consists of 30ug of mouse nerve growth factor, 0.5mg of mecobalamin, 0.5mg of adenosyl cobalamine, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, and is prepared for clinical use, wherein yang white acupoint, temple, sibai acupoint, yingxiang acupoint, juliao acupoint, dicang acupoint and Jiache acupoint of the affected side part are selected for acupoint injection, and the acupoint injection is carried out 1 time per day.
The treatment regimen of group 3 (7 days per treatment course, 4 treatment courses) included oral administration and point injection administration.
1. Regimen of simultaneous and/or sequential administration of oral drugs:
(1) Mannitol (125 ml/time, 2 times/day) and sodium aescinate (20 mg/time, 2 times/day) were administered intravenously for 14 days;
(2) Valacyclovir is administered intravenously at 0.3 g/dose, 2 times/day for 14 days;
(3) Dexamethasone is injected intravenously for 10 mg/day, and the dosage is 10 days;
(4) Oral citicoline sodium tablet (0.2 g/time, 3 times/day, 2-3 weeks of administration) and ginkgo leaf tablet (0.1 g/time, 3 times/day, 2 weeks of administration);
(5) After oral administration of prednisone acetate tablet (5 mg/time, 2 times/day for one week), prednisone acetate tablet (5 mg/time, 1 time/day for one week);
2. Acupoint injection dosing scheme:
(1) The single acupoint injection pharmaceutical composition consists of 30ug of mouse nerve growth factor, 0.5mg of mecobalamin, 0.5mg of adenosyl cobalamine, 5mg of dexamethasone and 1ml of lidocaine hydrochloride, and is prepared for clinical use, wherein yang white acupoint, temple, sibai acupoint, yingxiang acupoint, juliao acupoint, dicang acupoint and Jiache acupoint of the affected side part are selected for acupoint injection, and the acupoint injection is carried out 1 time per day.
(2) The nerve repairing cell protein extract freeze-dried preparation 130ug prepared in example 1 is injected into a single acupoint, dissolved in 2ml physiological saline, and selected from yang white acupoint, temple acupoint, four white acupoint, yingxiang acupoint, juliao acupoint, dicang acupoint and Jiache acupoint, contralateral temple acupoint and Dicang acupoint, and double-hand Hegu acupoint for acupoint injection for 1 time every day.
Efficacy assessment: satisfaction questionnaires and clinical scores House-Brakmann facial nerve function grading efficacy evaluation forms.
Sequence number Curative effect Efficacy evaluation criteria
1 Invalidation of No improvement or slight improvement after treatment
2 Effective and effective The affected part is obviously recovered, the affected eye is not tightly closed, and the angle of the mouth is slightly askew
3 Has obvious effect The affected part is basically normal, and the angle of the mouth is slightly inclined to the healthy side when laughing or the forehead lines are shallower than the healthy side when frowning
4 Healing of the wound The affected part is completely recovered to normal
Group 1: the treatment takes effect on the same day, and the ear pain of more than 70% of patients is obviously relieved, and the facial muscles of more than 40% of patients are improved, so that the mouth is askew and the face is not stiff. The effective rate of the traditional Chinese medicine for treating the disease is 70% and the effective rate of the traditional Chinese medicine for treating the disease is 40% in 7 days. The effective rate of the traditional Chinese medicine for treating the diseases is 80% and the obvious effect is 70% in 15 days. The cure rate of 30 days of treatment exceeds 80%.
Group 2: the medicine takes effect on the same day, and the ear pain of more than 80% of patients is obviously relieved, and the facial muscles of more than 50% of patients are improved, so that the mouth is askew and the face is not stiff. The effective rate of the traditional Chinese medicine for 7 days is 80% and the obvious rate is 50%. The effective rate of the traditional Chinese medicine for treating the diseases is 90% and the effective rate is 80% in 15 days. The cure rate of 30 days of treatment exceeds 90 percent, and basically has no sequelae, and the satisfaction degree is 100 minutes. The patient who is not cured is continuously treated for 1 to 3 courses of treatment according to the illness state and the medical history of the patient, and is basically cured. The patient follows the doctor's advice, pay attention to reduce or even avoid the influence of factors such as staying up all night, tired, external infection, catching cold, etc., basically no recurrence, the quality of life is showing and is improving.
Test group 3: the effect is quicker, and the effect of improving the facial muscle stiffness is more obvious. The medicine can be used for treating the patients on the same day, and more than 90% of the ear pain of the patients is obviously relieved, more than 60% of the facial muscles of the patients are improved, and the patients are askew and hard to face. The effective rate of the medicine for 7 days is 90% and the obvious rate is 70%. The obvious effect of the medicine is 90% after 15 days of treatment. The cure rate of 30 days of treatment is 100 percent, no sequelae exists basically, and the satisfaction degree is 100 minutes. The patient follows the doctor's advice, pay attention to reduce or even avoid the influence of factors such as staying up all night, tired, external infection, catching cold, etc., basically no recurrence, the quality of life is showing and is improving.
The above description of the embodiments of the present invention is not intended to limit the present invention, and those skilled in the art can make various changes or modifications according to the present invention without departing from the spirit of the present invention, and shall fall within the scope of the claims of the present invention.

Claims (10)

1. A pharmaceutical composition for preventing and treating acute phase facial paralysis, which contains any one or combination of dehydration drugs, antiviral drugs, anti-inflammatory drugs, nerve repair drugs and/or drugs for improving blood circulation.
2. The pharmaceutical composition for preventing and treating acute-phase facial paralysis according to claim 1, comprising any one of mannitol, sodium aescinate, acyclovir or valacyclovir, dexamethasone, prednisone, citicoline sodium, ginkgo leaf, murine nerve growth factor, mecobalamin, adenosylcobalamin, or a combination thereof.
3. The pharmaceutical composition for preventing and treating acute phase facial paralysis according to any one of claims 1-2, which consists of a single oral pharmaceutical composition and a single acupoint injection pharmaceutical composition.
4. A pharmaceutical composition according to any one of claims 1-3, comprising 125-250ml mannitol, 10-20mg sodium aescinate, 0.3-0.4g acyclovir or valacyclovir, 1-5mg dexamethasone or prednisone tablet, 0.2-0.5mg citicoline sodium tablet, 0.1-0.2g ginkgo leaf, 30-90ug murine nerve growth factor, 0.5-1.0mg mecobalamin, 0.1-0.5mg cobamamide, 2-5mg dexamethasone or a combination thereof.
5. The pharmaceutical composition of any one of claims 1-4, which is administered orally in a regimen comprising:
(1) Mannitol (125-250 ml/time, 1-2 times/day) and sodium aescinate (20 mg/time,
1-2 times per day), and the medicine is used for 7-14 days;
(2) Intravenous acyclovir or valacyclovir 0.3 g/time, 2 times/day for 7-14 days;
(3) Dexamethasone is injected intravenously (5-10 mg/day, 7-10 days of administration);
(4) Oral citicoline sodium tablet (0.2 g/time, 3 times/day, administration for 2-3 weeks) and ginkgo leaf tablet (0.1-0.2 g/time, 3 times/day, administration for 2 weeks);
(5) After oral administration of prednisone acetate tablet (5 mg/time, 2 times/day for one week), prednisone acetate tablet (5 mg/time, 1 time/day for one week);
6. the pharmaceutical composition according to any one of claims 1-5, wherein the pharmaceutical composition for single acupoint injection consists of 30-90ug of murine nerve growth factor, 0.5-1.0mg of mecobalamin, 0.1-0.5mg of adenosylcobalamin, and 2-5mg of dexamethasone.
7. The pharmaceutical composition of any one of claims 1-6, optionally containing 100-300mg of any one of or a combination of a neural repair cell protein extract and/or a neural repair protein composition with repair efficacy for a single point injection.
8. The pharmaceutical composition of any one of claims 1-7, wherein the injection is performed by selecting yang white acupoint, temple, four white acupoint, yingxiang acupoint, juliao acupoint, dicang acupoint and buckstay acupoint of the affected side.
9. Use of a pharmaceutical composition according to any one of claims 1-8 for the manufacture of a medicament for the prevention and treatment of acute phase facial paralysis, wherein the pharmaceutical composition for the prevention and treatment of acute phase facial paralysis comprises any one or a combination of a dehydration-type medicament, an antiviral medicament, an anti-inflammatory medicament, a nerve repair medicament and/or a medicament for improving blood circulation.
10. A therapeutic regimen for treating acute phase facial paralysis, the therapeutic regimen comprising a pharmaceutical composition for preventing and treating acute phase facial paralysis according to any one of claims 1-8, the pharmaceutical composition for preventing and treating acute phase facial paralysis comprising any one of or a combination of a dehydration-type drug, an antiviral drug, an anti-inflammatory drug, a nerve repair drug, and/or a blood circulation improving drug.
CN202311159238.4A 2022-09-09 2023-09-09 Pharmaceutical composition for preventing and treating acute facial paralysis and application thereof Pending CN117679519A (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CN202211101693 2022-09-09
CN202211101347 2022-09-09
CN2022111016934 2022-09-09
CN2022111013476 2022-09-09

Publications (1)

Publication Number Publication Date
CN117679519A true CN117679519A (en) 2024-03-12

Family

ID=90127306

Family Applications (6)

Application Number Title Priority Date Filing Date
CN202311159241.6A Pending CN117679520A (en) 2022-09-09 2023-09-09 Pharmaceutical composition for preventing and treating facial paralysis in sequela stage and application thereof
CN202311159238.4A Pending CN117679519A (en) 2022-09-09 2023-09-09 Pharmaceutical composition for preventing and treating acute facial paralysis and application thereof
CN202311159255.8A Pending CN117679521A (en) 2022-09-09 2023-09-09 Pharmaceutical composition for preventing and treating facial nerve micro-clamping pressure syndrome and application thereof
CN202311159233.1A Pending CN117679518A (en) 2022-09-09 2023-09-09 Pharmaceutical composition for preventing and treating convalescence facial paralysis and application thereof
CN202311159251.XA Pending CN117679649A (en) 2022-09-09 2023-09-09 Application of radio frequency device in joint movement for treating facial paralysis
CN202311159266.6A Pending CN117679522A (en) 2022-09-09 2023-09-09 Pharmaceutical composition for preventing and treating nervous system lesions and application thereof

Family Applications Before (1)

Application Number Title Priority Date Filing Date
CN202311159241.6A Pending CN117679520A (en) 2022-09-09 2023-09-09 Pharmaceutical composition for preventing and treating facial paralysis in sequela stage and application thereof

Family Applications After (4)

Application Number Title Priority Date Filing Date
CN202311159255.8A Pending CN117679521A (en) 2022-09-09 2023-09-09 Pharmaceutical composition for preventing and treating facial nerve micro-clamping pressure syndrome and application thereof
CN202311159233.1A Pending CN117679518A (en) 2022-09-09 2023-09-09 Pharmaceutical composition for preventing and treating convalescence facial paralysis and application thereof
CN202311159251.XA Pending CN117679649A (en) 2022-09-09 2023-09-09 Application of radio frequency device in joint movement for treating facial paralysis
CN202311159266.6A Pending CN117679522A (en) 2022-09-09 2023-09-09 Pharmaceutical composition for preventing and treating nervous system lesions and application thereof

Country Status (2)

Country Link
CN (6) CN117679520A (en)
WO (6) WO2024051847A1 (en)

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1036973C (en) * 1993-10-14 1998-01-14 宋定邦 Nerve block injection
CN102631667B (en) * 2012-04-19 2013-10-02 赵廷宝 Nerve regeneration promotion injection and preparation method thereof
CN202682577U (en) * 2012-06-28 2013-01-23 四川旭康医疗电器有限公司 Household multifunctional comprehensive therapeutic apparatus
CN102988403A (en) * 2012-12-06 2013-03-27 祁建春 Injection medicine composition used for treating facial paralysis in acute stage
US20140296948A1 (en) * 2013-03-27 2014-10-02 Hitops Gmbh New therapy of cancer with pulsed radio frequency
CN103638250B (en) * 2013-12-23 2015-08-12 李宣东 One treats prosopoplegic Chinese medicine preparation and preparation method thereof
US20150209390A1 (en) * 2014-01-27 2015-07-30 Snu R&Db Foundation Method and pharmaceutical composition comprising adipose stem cell extract for treating or preventing neurologic disease
CN204233210U (en) * 2014-11-15 2015-04-01 周国明 Full frequency band combined type Wicresoft radio frequency pain therapeutic equipment
CN104587448A (en) * 2015-01-28 2015-05-06 赵廷宝 Method for intrathecally injecting nerve regeneration promoting injection
CN104771602A (en) * 2015-04-17 2015-07-15 刘振亮 Medicine for treating facioplegia and preparation method thereof
CN106265678B (en) * 2016-07-18 2019-06-04 陕西省中医医院 A kind of plaster and preparation method thereof for facial paralysis
CN108743366A (en) * 2018-02-28 2018-11-06 上海衡晟医院投资管理有限公司 The method of biological liquid drugs injection activation auditory nerve
CN209075855U (en) * 2018-09-27 2019-07-09 金泽 Facial paralysis illness oral cavity intramedullary expansion and acupoint stimulation electronic pulse therapeutic instrument
CN111419866A (en) * 2020-03-02 2020-07-17 南通大学 Application of miR-29a-3p in preparation of medicine for treating peripheral nerve injury
US11806545B2 (en) * 2020-10-23 2023-11-07 Nextep BV Therapy of eye conditions with pulsed radio frequency
CN113082043A (en) * 2021-04-20 2021-07-09 王化兰 Medicine for treating facial paralysis by traditional Chinese medicine acupoint injection

Also Published As

Publication number Publication date
CN117679520A (en) 2024-03-12
CN117679649A (en) 2024-03-12
WO2024051845A1 (en) 2024-03-14
WO2024051844A1 (en) 2024-03-14
WO2024051846A1 (en) 2024-03-14
WO2024051848A1 (en) 2024-03-14
WO2024051843A1 (en) 2024-03-14
WO2024051847A1 (en) 2024-03-14
CN117679521A (en) 2024-03-12
CN117679522A (en) 2024-03-12
CN117679518A (en) 2024-03-12

Similar Documents

Publication Publication Date Title
US11517604B2 (en) Method for preparing Plectranthus amboinicus fraction having anti-arthritis activity
Tang et al. Effects of dl-3-n-butylphthalide on serum VEGF and bFGF levels in acute cerebral infarction
US20230225971A1 (en) Stem cell-derived exosomes containing pain regulators, and uses thereof
CN113413461A (en) Medicine for resisting senile dementia and its preparing method
JPH05186360A (en) Therapeutic agent for allergic disease and production of acanthopanax senticosus extract
CN117679519A (en) Pharmaceutical composition for preventing and treating acute facial paralysis and application thereof
CN107496525B (en) Traditional Chinese medicine composition for treating cancer pain diseases and application thereof
CN114767729A (en) Application of medicinal composition of Qudesheng snake or preparation thereof in preparation of medicines for preventing, relieving, and assisting in treating or treating facial spasm or endogenous wind
CN108743571A (en) Prevent, treat the pharmaceutical composition and preparation method thereof of epilepsy
TWI794335B (en) Use of Pien Tze Huang and its preparations in the treatment of sequelae of cerebral apoplexy
EP4082556A1 (en) Compound preparation for neuranagenesis, and preparation method therefor and use thereof
CN115624543B (en) Medicine for treating migraine, pharmaceutical composition, preparation method and pharmaceutical application thereof
CN107854620A (en) The Chinese medicine composition of cognition dysfunction and its application after a kind of improvement brain damage
CN115192684B (en) A Chinese medicinal composition for relieving or treating pain, and its preparation method
CN102204956A (en) Chinese medicinal composition used at stroke recovery period and preparation method thereof
RU2420281C2 (en) Method of treating diseases caused by herpes virus
CN107158205B (en) A pharmaceutical composition for treating hypertension
Bennett The introduction of curare into clinical medicine: present and potential usefulness
CN111671819A (en) Pure traditional Chinese medicine transdermal liniment for treating hemiplegia and preparation method thereof
CN114767724A (en) Application of aster tataricus powder extract in preparation of medicine for treating chronic rhinitis
CN112755010A (en) Application of menthone in preparing medicine for treating rheumatoid arthritis
CN113750134A (en) Traditional Chinese medicine microecological preparation for patients with ischemic stroke
CN112263604A (en) Tibetan medicine five-ingredient nectar composition as well as preparation method and application thereof
ITRM20130006A1 (en) HOMEOPATHIC MEDICATION INCLUDING THE NERVOUS GROWTH FACTOR (NGF), ITS PROCESS OF PROCESSING AND OBTAINING.
CN112569288A (en) NMN pharmaceutical composition for cerebral apoplexy

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication