CN106177446A - A kind of Chinese medicine preparation for treating idiopathic facial palsy - Google Patents

A kind of Chinese medicine preparation for treating idiopathic facial palsy Download PDF

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CN106177446A
CN106177446A CN201610782582.2A CN201610782582A CN106177446A CN 106177446 A CN106177446 A CN 106177446A CN 201610782582 A CN201610782582 A CN 201610782582A CN 106177446 A CN106177446 A CN 106177446A
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rhizoma
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facial
radix
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CN106177446B (en
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李妍怡
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GANSU PROVINCIAL HOSPITAL OF TRADITIONAL CHINESE MEDICINE
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    • A—HUMAN NECESSITIES
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    • 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)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/232—Angelica
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
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    • A61K35/648—Myriapods, e.g. centipedes or millipedes
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    • 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)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
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    • 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)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/237—Notopterygium
    • 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)
    • A61K36/29—Berberidaceae (Barberry family), e.g. barberry, cohosh or mayapple
    • A61K36/296—Epimedium
    • A—HUMAN NECESSITIES
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    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/481—Astragalus (milkvetch)
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    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/484—Glycyrrhiza (licorice)
    • 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)
    • A61K36/88—Liliopsida (monocotyledons)
    • 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)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/888—Araceae (Arum family), e.g. caladium, calla lily or skunk cabbage
    • 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)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • A61K36/8969—Polygonatum (Solomon's seal)
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration

Abstract

A kind of Chinese medicine preparation for treating idiopathic facial palsy, is that Radix Glycyrrhizae is crude drug, and common process and adjuvant according to pharmacy of Chinese materia medica are prepared as oral preparations with Radix Angelicae Sinensis, Rhizoma Chuanxiong, Scorpio, Scolopendra, Rhizoma Typhonii, Rhizoma Et Radix Notopterygii, Rhizoma Polygonati, the Radix Astragali, Rhizoma Curculiginis, Herba Epimedii.Clinical experiment shows, Chinese medicine preparation of the present invention has significant clinical efficacy to treatment idiopathic facial palsy, it is substantially shorter the course for the treatment of, patient facial region function of nervous system and every facial paralysis symptom can be effectively improved, significantly improve facial body and the social function of patient, improve the facial disabled degree of patient, promote the recovery of facial paralysis patient's facial muscle muscular strength.The Chinese herbal medicine of this drug utilization no side effects is crude drug, safely, effectively, has no side effect human body, is worth promotion and application clinically.

Description

A kind of Chinese medicine preparation for treating idiopathic facial palsy
Technical field
The present invention relates to a kind of Chinese medicine preparation treating idiopathic facial palsy, belong to technical field of Chinese medicine.
Background technology
Idiopathic facial palsy (Idiopathic facial palsy) is also known as facial neuritis (facial Neuritis), Bell's palsy (Bell ' s palsy), be because of peripheral caused by nervus facialis nonspecific inflammation in stylomastoid foramen Neuroparalysis, clinically many referred to as peripheral facial paralysiies.Common symptom is that volume stricture of vagina disappears, it is impossible to wrinkle volume is frowned, and palpebral fissure can not close Closing or dysraphism, during eye closing, double eyeball outwards rotates over, and exposes white sclera；Nasolabial fold shoals, ptosis of labial angle, time grinningly Bicker is askew to strong side；Air-blowing, gas leakage of whistling, food is easily detained disease side gums etc..The idiopathic facial palsy cause of disease is the brightest, many Owing to virus infection, autonomic nervous function shakiness cause local nerve nutrient vessel spasm, neural ischemia, edema cause nervus facialis In bone facial canal, pressurized occurs that facial muscle is paralysed.
In China, the annual sickness rate of facial neuritis is (26-34)/100,000, and prevalence is about 2,58/,100,000, age of onset Most commonly seen with 20～40 years old, male is common compared with women, has the patient of 75%～90% to fully recover, but still has the trouble of 15%～20% Person leaves facial nerve function obstacle in various degree, as facial spasm, facial muscle synkinesia, the unusual sense of taste and crocodile tear are levied Deng.Idiopathic facial palsy is typically acute attack, can spontaneous remission, not threat to life, be common clinical and multiple Sick.Although idiopathic facial palsy is without lethal danger, after ill, affect image appearance, cause bigger to patient's body and mind Misery, make patient produce huge mental pressure, show as the symptom such as fear, anxiety, and then it is normal to have had a strong impact on patient Work and life.The effective treatment means the most actively inquiring into idiopathic facial palsy is the main of current medical personnel Task.
The traditional Chinese medical science is thought, idiopathic facial palsy disease is due to work excessively, positive QI-insufficiency, blood virtual loss, and venation is hollow, Battalion defends the heresy of imbalance, striae of the skin and muscles being loose, weakened defensive QI, wind and cold or wind heat and attacks human body in an opponent's defence, above alters and hangs out in face, flesh of contaminating Skin, enters through appoplexy involving the collateral, so that face sun bright, few positive two blocks through passages through which vital energy circulates, muscles along the regular meridians loses supports, and muscle vertical delaying does not receives and fall ill.Therefore treatment The method of upper many dispelling wind and removing obstruction in the collateral, also can coordinate acupuncture, massage etc. to treat.Medicine such as adrenocortical hormone that Western medicine is conventional (fill in Meter Song, hydrocortisone, prednisone etc.), antiviral agents, trophic nerve medicine (vitB6, vitB1, vitB12 etc.).Wherein hormone Being the most frequently used medicine, although application hormone can alleviate the inflammatory edema of nervus facialis, relief of symptoms in early days, but hormone exists many Contraindication and side effect.
Our seminar is in long-term clinical practice, according to the Pathogenesis Theory of the traditional Chinese medical science and combine clinical development and go out treatment spy Send out " dispel the wind granule " of peripheral facial paralysis, be by Radix Angelicae Sinensis, Rhizoma Chuanxiong, Scorpio, Bombyx Batryticatus, the Radix Astragali, Scolopendra, Radix Isatidis, the Radix Paeoniae Alba, Radix Glycyrrhizae Deng composition (" western Chinese medicine " 2013 volume 26 the 10th phase the 82-83 page).Clinical test results shows, should " dispel the wind granule " exist Treatment idiopathic facial palsy acquirement good therapeutic effect: treatment group cure rate 54.82%, obvious effective rate 29.95%, matched group cure rate 41.58%, obvious effective rate 26.84%, comparitive study between 2 groups, difference statistically significant (P ＜ 0.01).Treatment group total effective rate is high In matched group, difference statistically significant (P ＜ 0.05).Although, we achieve certain achievement under study for action, but, I Still think that this achievement in research is not ideal.
Summary of the invention
The problem that it is an object of the invention to exist for prior art, a kind of curative effect significantly more treatment idiopathic of body Prosopoplegic Chinese medicine preparation.
The present invention is on the basis of " dispel the wind granule " that this seminar develops, by the disease sick to idiopathic facial palsy Because having done further in-depth study, on the basis of " dispel the wind granule " prescription, by adjusting prescription, the ratio of each component, enter And improve the mechanism of action of medicine, to reaching more preferable therapeutic effect.
The Chinese medicine preparation of the idiopathic facial palsy of the present invention, is with Radix Angelicae Sinensis, Rhizoma Chuanxiong, Scorpio, Scolopendra, Rhizoma Typhonii, Qiang Living, Rhizoma Polygonati, the Radix Astragali, Rhizoma Curculiginis, Herba Epimedii, Radix Glycyrrhizae is that crude drug carries out prescription.The present invention on the basis of " dispel the wind granule " prescription, Delete Bombyx Batryticatus, Radix Isatidis, the Radix Paeoniae Alba three taste, add again Rhizoma Typhonii, Rhizoma Et Radix Notopterygii, Rhizoma Polygonati, Rhizoma Curculiginis, the Herba Epimedii five tastes simultaneously.Wherein Radix Angelicae Sinensis, Rhizoma Chuanxiong nourishing blood and promoting blood circulation；Scorpio, Scolopendra are expellingged wind and relieving convulsion, removing obstruction in the collateral to relieve pain；Radix Astragali benefiting QI for strengthening the superficies；Rhizoma Typhonii, acrid in the mouth, sweet, property Temperature, poisonous.Return stomach, Liver Channel.Having the expectorant that dispels the wind, arresting convulsion is jerked, detoxicating and resolving stagnation of pathogens, effect of pain relieving.Rhizoma Et Radix Notopterygii, warm in nature, dispelling cold and dampness, it is used for Affection of exogenous wind-cold, have a headache lossless, cold-damp numbness, upper limb rheumatalgia.Rhizoma Polygonati, sweet, flat.Return spleen, lung, kidney channel.There is boosting qi and nourishing yin, strong Spleen, lung moistening, the merit of kidney tonifying.Rhizoma Curculiginis, warm in nature, acrid in the mouth is micro-salty.Enter kidney, Liver Channel.Function: there is the kidney warming sun, the effect of strengthening bone and muscle.Celestial spirit Spleen, also known as Herba Epimedii, warm in nature, acrid in the mouth, enter liver, kidney channel.There is kidney invigorating and YANG supporting, expelling wind and removing dampness effect.The present invention is white by increasing Radix Aconiti Lateralis Preparata, Rhizoma Et Radix Notopterygii, Rhizoma Polygonati, Rhizoma Curculiginis, the Herba Epimedii five tastes, further enhance the effect that QI invigorating consolidates so that it is with Radix Angelicae Sinensis, Rhizoma Chuanxiong, Scorpio, Scolopendra, after cooperation, dispel the wind, detoxify, the function of dredging collateral is greatly strengthened, idiopathic facial palsy disease is controlled Therapeutic effect is significantly improved.
In Chinese medicine preparation of the present invention, each raw material carries out proportioning by following weight portion: Radix Angelicae Sinensis 40-50 part, Rhizoma Chuanxiong 15-25 part, Scorpio 3-8 part, Scolopendra 3-8 part, Rhizoma Typhonii 6-12 part, Rhizoma Et Radix Notopterygii 6-12 part, Rhizoma Polygonati 15-22 part, Radix Astragali 15-22 part, Rhizoma Curculiginis 6-12 Part, Herba Epimedii 6-12 part, Radix Glycyrrhizae 3-8 part.
Optimum ratio: Radix Angelicae Sinensis 43-47 part, Rhizoma Chuanxiong 18-22 part, Scorpio 5-6 part, Scolopendra 5-6 part, Rhizoma Typhonii 8-10 part, Qiang 8-10 part alive, Rhizoma Polygonati 18-20 part, Radix Astragali 18-20 part, Rhizoma Curculiginis 8-10 part, Herba Epimedii 8-10 part, Radix Glycyrrhizae 5-8 part.
Optimum proportioning: Radix Angelicae Sinensis 45 parts, Rhizoma Chuanxiong 20 parts, Scorpio 5 parts, Scolopendra 5 parts, Rhizoma Typhonii 10 parts, Rhizoma Et Radix Notopterygii 10 parts, Rhizoma Polygonati 20 Part, the Radix Astragali 20 parts, Rhizoma Curculiginis 10 parts, Herba Epimedii 10 parts, 5 parts of Radix Glycyrrhizae.
The Chinese medicine preparation of the present invention can be prepared as oral preparations according to the common process of pharmacy of Chinese materia medica and adjuvant, as oral administration Preparation is capsule, granule, tablet, pill etc..
Illustrate that the therapeutic effect of idiopathic facial palsy is done specifically by pharmaceutical preparation of the present invention below by clinical data Explanation.
1 clinical data
1.1. case selection standard
1.1.1 tcm diagnosis standard
The national teaching material " science of acupuncture and moxibustion " of reference regular higher education " 15 " (Shi Xuemin edits, China Traditional Chinese Medicine Publishing House, and 2007 Year).
(1) onset is unexpected, and spring and autumn be many, often have after catching cold history or having side buccal, in ear, ear the pain at Wangue or Heat.
(2) side face is stiff, numb, sheds tears, and volume stricture of vagina disappears, and nasolabial fold shoals, and eye can not close, and bicker is led to strong side Draw.
(3) can not close one's eyes in side, the drum cheek, waits action grinningly.
(4) electromyogram can behave as exception.
1.1.2 Western medicine diagnose standard
With reference to regular higher education " 15 " National planning teaching material " neurological " the 5th edition, (Wang Weizhi edits, people's health Publish and shut out, 2004).
(1) medical history: onset is anxious, blowing history of often suffering from cold, or has virus infection history.
(2) performance: side facial expression muscle is paralysed suddenly, sick side volume stricture of vagina disappears, and palpebral fissure can not close, and nasolabial fold shoals, Ptosis of labial angle. the drum cheek, leak gas when whistling, food is easily stranded between the tooth cheek of disease side, can accompany 2/3 gustatory anesthesia before the tongue of disease side, listen Feel allergy, many tears etc..
(3) brain CT, MRI checks normal.
Grade scale
Use House-Brackmann facial nerve function grade form[1], this table is by Head and neck tumour otorhinolaryngology association of the U.S., face Sacred disease committee of portion is recommended, and the evaluation criterion as face nerve functional rehabilitation uses.
I level: function is normal；The all regional functions of face are normal；Be equivalent to face function 100%.
II grade: slight dysfunction；Overall: to perceive slight facial muscle when examining unable, can have the slightest Synkinesia.Static symmetric and tension force are normal, more than volume moderate well moving during motion, and eye is micro-firmly can be the most closed, Fond of food that is not salty micro-asymmetric；Be equivalent to face function 76-99%.
III grade: moderate dysfunction；Overall both sides difference is obvious, but lossless face, perceives the most serious associated Motion, contracture and (or) hemifacial spasm；Time static, symmetry and tension force are normal.The motion that motion volume is mild to moderate, ophthalmically acceptable power Can be the most closed, mouth with strength time slight force weak；Be equivalent to face function 51-75%.
IV grade: middle severe dysfunction；Overall the most unable and (or) disfiguring asymmetric, static symmetric and tension force are just Often, during motion volume without motion, eye can not be the most closed, mouth with strength time asymmetric；Face function 26-50%.
V grade: severe dysfunction；The overall motion just can perceived；Static asymmetric, during motion, volume is without motion, and eye is not Can be the most closed, micro-motion fond of food that is not salty；Be equivalent to face function 1-25%.
VI grade: complete paralysis；Without any motion；Face function 0%.
1.1.4 staging
In early days (acute stage): morbidity started to 15 days；
Mid-term (convalescent period): 16 days to 6 months (morbidity first quarter moon---the related motion of facial muscle occurs)；
Late period (linkage phase and spasm period): after falling ill 6 months (after the related motion of facial muscle occurs).
1.1.5 case inclusive criteria
(1) tcm diagnosis standard and the Western medicine diagnose standard of above-mentioned idiopathic facial palsy are met.
(2) male or female, the age is between 18-70 year
(3) this researcher is participated in after Informed choice is agreed to voluntarily.
(4) do not meet following exclusion standard person simultaneously.
1.1.6 case exclusion standard
(1) tcm diagnosis standard and Western medicine diagnose standard person are not met.
(2) having Ipsilateral mastoidea pain, external auditory meatus, auricle are felt to go down and external auditory meatus, tympanum herpes (Hunt syndrome) Person.
(3) person that is diagnosed as Guillain Barre syndrome.
(4) otitis media, labyrinthitis, the otogenic facial paralysis of mastoiditis and parotitis, meningitis, rear cranium it are secondary to The Peripheral Facial Paralysis Patients that nest tumor, suppurative mandibular lymphadenitis cause.
(5) Traumatic Facial damages the wounded.
(6) severe infection or hypertension, the bad person of blood glucose control.
(7) heart, cerebrovascular or liver, kidney, lung and hemopoietic system or other system serious disease are merged, or psychosis, puerperium The patient of phase.
(8) accepted or accepted other treatment, the index observer of this research may have been affected.
1.1.7 reject and come off standard
(1) the peripheral facial paralysis person being secondary to other diseases (such as otitis media, tumor etc.) it is diagnosed as after including packet in.
(2) bolter voluntarily.
(3) treatment and observer, the most whole course of therapy person, observation of curative effect are not completed by regulation because of a variety of causes Record imperfect person, not by the infull person of predetermined treatment or data.
(4) observe in naturally come off, person lost to follow-up.
(5) experimenter's compliance is poor, and the person that should not continue reception test.
1.2 physical data
All MethodsThe cases enrolled 346 examples, derive from 2008～Gansu Provincial Hospital of Traditional Chinese Medicine in 2016 is in hospital and outpatient, wherein reject And 19 examples that come off, totally 327 examples complete whole research process, and patient is divided into treatment group 167 example at random, matched group 160 example, and two Group patient's ordinary circumstance compares and is shown in Table 1～5.
Table 1-5 shows: two groups of Genders, age, the course of disease, the overall classification of H-B grading scale, face disabled index (FDI) amounts Table is marked, no significant difference (P＞ 0.05), there is comparability.
2. test method
2.1 Therapeutic Method
Matched group: oral meticorten 30mg, 1 time/d, continuous 7 days, the gradually decrement at 7-10 days subsequently；Oral compound vitamin B 2 Sheet, 3 times/d；Intramuscular injection vitamin B12, 500ug, 1 time/d；Chloromycetin eyedrops, every day eye drip for several times, to protect cornea.
Treatment group: have granular preparation prepared by prescription of the present invention；Usage and dosage: 15g/ time, takes after mixing it with water by 3 times/day.2 groups all with Within 10 days, it is 1 course for the treatment of, general treatment 2～6 course for the treatment of.
2.2 observation index and method
2.2.1 safety observations
(1) general health check-up project；
(2) blood, urine, feces routine conventional, biochemical, Electrocardioscopy check, to get rid of severe primary disease in time testing into group Patient.Record adverse effect simultaneously.
2.2.2 electrophysiological index
Electromyography (EMG): use and detect strong side and the orbicularis oculi of Ipsilateral, orbicularis oris respectively with core round needle electrode, sees When examining insertion current potential, muscle relaxation spontaneous potential and light firmly time the waveform of motor unit potential, time limit, wave amplitude and maximum firmly receive Current potential is raised during contracting.
2.2.3 efficacy evaluation
(1) the overall grading scale of House-Brackmann facial nerve function, content sees attached list 1.
(2) facial paralysis grading grade form: improve this table by the symptom and sign observing treatment Patients Before And After, And the scoring of each group of patient changed compare analysis, gauge content for details see attached table 2.
(3) disabled index (FDI) scale of face: be divided into somatic function and social life function two parts, according in scale The problem proposed, by body and the change of socio-psychology-status of patient's facial nerve disease, is carried out disabled degree and curative effect Evaluate.FDI scale has 10 problems, 1 ~ 5 reflection somatic function (FDIP), 6 ~ 10 reflection social life functions (FDIS), this table is simple and easy to do, on face delayed ischemic neurological deficits and thus bring social mentality impact carry out thoroughly evaluating, Therapeutic evaluation aspect is significant.Gauge content for details see attached table 3.
2.3 efficacy assessment standard
Efficacy of Traditional Chinese Medicine evaluation criterias etc. use " peripheral the god that department of neurology Professional Committee of CAIM (Chinese Association Of Integrative Medicine) works out Combination of Chinese and Western medicine evaluation and criterion of therapeutical effect (draft) through paralysis "[2]Evaluate.
Recovery from illness: HB scale I grade；The scoring of facial paralysis grading is 100 points.
Effective: HB scale II grade；The scoring of facial paralysis grading is at 75 points and above, less than 100 points.
Effective: HB scale III grade；Facial paralysis grading is marked below 75 points, more than 50 points.
Invalid: HB scale IV grade and following；Facial paralysis grading is marked 50 points and less.
2.4 statistical method
Application SPSS13.0 software carries out data process, and normal distribution data results uses mean ± standard deviation (± s) to represent, partially State data results uses median (interquartile range) M (Q) to represent.Quantitative data uses t inspection and rank test, qualitative money Material uses χ2Inspection and rank test.P＜ 0.05(bilateral) think that difference is statistically significant.
3 results
3.1 curative effect marking scales classifications are compared
3.1.1House-Brackmann the overall classification of facial nerve function is compared
Table 6 shows, after the treatment for the treatment of group, the overall classification of House-Brackmann facial nerve function is compared before treatment, and difference has Statistical significance (P＜ 0.01), illustrate that treatment rear face function of nervous system makes moderate progress before relatively treating.
Table 7 shows, after treatment of control group, the overall classification of House-Brackmann facial nerve function is compared before treatment, and difference has Statistical significance (P＜ 0.01), illustrate that treatment rear face function of nervous system makes moderate progress before relatively treating.
Table 8 shows, after treatment, two groups of patient's overall classifications of House-Brackmann facial nerve function are compared, and difference has system Meter meaning (P＜ 0.01), illustrate that treatment group is improved facial nerve function and is better than matched group.
3.1.2 the scoring of facial paralysis grading is compared
Table 9 shows, after the treatment for the treatment of group, the facial paralysis degree of every symptom all makes moderate progress before relatively treating, and difference all has system Meter meaning (P＜ 0.01).
Table 10 shows, after treatment of control group, the facial paralysis degree of every symptom all makes moderate progress before relatively treating, difference The most statistically significant (P＜ 0.01).
Table 11 shows, after treatment, the facial paralysis degree scoring of two groups of patient's individual event symptoms is compared, and difference is all without statistics Meaning (P＞ 0.05).
Table 12 shows, after two groups of patient treatments, neural paralysis grading total score all increases before relatively treating, difference Statistically significant (P＜ 0.01)；Treating neural paralysis grading total score treatment group below and be higher than matched group, difference has system Meter meaning (P＜ 0.01).Prompting treatment group is improved the degree of facial nerve function and is substantially better than matched group.
3.1.3 (± S) is compared in the scoring of face disabled index (FDI)
Table 13 shows, two groups of patient treatment back body function total scores all increase before relatively treating, difference statistically significant (P ＜ 0.01)；Treatment back body function total score treatment group higher than matched group, difference statistically significant (P＜ 0.01).
Table 14 shows, after two groups of patient treatments, social function total score all increases before relatively treating, and difference has statistics to anticipate Justice (P＜ 0.01)；After treatment social function total score treatment group be higher than matched group, difference statistically significant (P＜ 0.01).
Two groups of patient's electromyogram (ENG) results contrast after 3.2 treatments
Table 15 shows, after treatment, treatment group EMG recovers normal person 57.36%, and matched group 42.63%, two groups are compared, and difference has statistics Meaning (P＜ 0.01).
3.3 comparitive study
3.3.1 two groups of patient's comparitive study
Table 16 shows, treatment group cure rate 58.68%, obvious effective rate 26.95%, matched group cure rate 40.62%, obvious effective rate 25.62%, Comparitive study between two groups, difference statistically significant (P＜ 0.01).Treatment group total effective rate is higher than matched group, and difference has statistics Meaning (P＜ 0.05).
3.3.2 difference patient's comparitive study by stages
Table 17 shows, treatment group early stage, mid-term, the cure rate of patients with terminal are respectively 66.27%, 49.02%, 57.58%, three groups Between comparitive study, difference statistically significant (P＜ 0.05).
Table 18 shows, matched group early stage, mid-term, the cure rate of patients with terminal are respectively 56.18%, 38.60%, 15.91%, Comparitive study between three groups, difference statistically significant (P＜ 0.01).
Table 19 shows, in early days with patients with terminal treatment group and matched group comparitive study, no significant difference (P＞ 0.05)；Treatment group patients with terminal cure rate 57.58%, obvious effective rate 24.24%, matched group patients with terminal cure rate 17.65%, effective Rate 14.71%, two groups of patient's comparitive study, difference statistically significant (P＜ 0.01).Show that treatment group is to patients with terminal curative effect It is better than matched group.
3.4 safety observations
It is showed no untoward reaction before and after two groups of patient treatments.Before and after treatment, blood, urine, feces routine conventional, biochemical, electrocardiogram are showed no The most abnormal.
Above-mentioned clinical data shows, after two groups of patient treatments, the overall classification of H-B face nerve function is compared before treatment, poor Different the most statistically significant (P＜ 0.01), the most all improvement of face nerve function to patient of two kinds of therapies are described.Treatment group After treatment H-B classification reach I grade and II patient be 64.47% and 29.34%, after treatment of control group, H-B classification reaches I grade and II Patient be 43.13% and 25.63%, two groups are compared, difference statistically significant (P＜ 0.01), illustrate that treatment group improves patient Facial nerve function is substantially better than matched group, shows that a kind of compositions treating idiopathic facial palsy can be effectively improved facial paralysis and suffer from The facial nerve function of person.
Clinical data also shows, before and after two groups of patient treatments, the facial paralysis degree scoring of each individual event symptom is compared, poor Different the most statistically significant (P＜ 0.01), before after treatment, two groups of patient's facial paralysis grading total scores are relatively treated the most Improve, difference statistically significant (P＜ 0.01), illustrate that two kinds of therapies all can be effectively improved every facial paralysis symptom, as Nasolabial fold shoals, palpebral fissure is asymmetric, simultaneously facilitates the recovery of the adjoint sensory disturbance such as hypercacusis, hypogeusia, thus Improving whole facial nerve function on the whole, reduction facial paralysis is on daily life and the impact of social life, neural numb after treatment Numbness grading total score treatment group be higher than matched group, difference statistically significant (P＜ 0.01).Treatment group improvement face god is described Degree through benumbing is better than matched group, shows that a kind of compositions treating idiopathic facial palsy can be effectively improved facial paralysis patient Facial paralysis symptom.
Clinical data shows, after treatment, treatment group EMG recovers normal person (60.45%) higher than matched group (41.53%), two groups Relatively, difference have significant difference (P＜ 0.01).Show that a kind of compositions treating idiopathic facial palsy promotes facial paralysis The recovery of patient's facial muscle muscular strength.
Clinical data shows, treatment group cure rate 58.68%, obvious effective rate 26.95%, matched group cure rate 40.62%, effective Rate 25.62%, comparitive study between two groups, difference statistically significant (P＜ 0.01).Treatment group total effective rate is higher than matched group, Difference statistically significant (P＜ 0.05).Illustrate that the curative effect for the treatment of group is better than matched group, show that one treats idiopathic face god Compositions treatment idiopathic facial palsy through benumbing has significant clinical efficacy.
Difference patient's comparitive study by stages, treatment group early stage, mid-term, the cure rate of patients with terminal be respectively 66.27%, 49.02%, 57.58%, the comparitive study between three groups, difference statistically significant (P＜ 0.05).Matched group early stage, mid-term, evening The cure rate of phase patient is respectively 60.76%, 42.55%, 17.65%, the comparitive study between three groups, difference statistically significant (P ＜ 0.01).Illustrate patient is got over early treatment, more can obtain significant curative effect.
Two kinds of therapies in early days and patient's comparitive study in mid-term, no significant difference (P＞ 0.05), treatment group is late Phase patient's cure rate 57.58%, obvious effective rate 24.24%, matched group patients with terminal cure rate 17.65%, obvious effective rate 14.71%, two groups Patient's comparitive study, difference statistically significant (P＜ 0.01)；Illustrate that treatment group is better than matched group to the curative effect of patients with terminal, Show that a kind of compositions treating idiopathic facial palsy also has significant curative effect to advanced refractory patient.
Detailed description of the invention
Below by specific embodiment, prescription and the preparation of Chinese medicine preparation of the present invention are described further.
Embodiment 1, the preparation of granule
Proportioning raw materials: in parts by weight
Radix Angelicae Sinensis 45 parts, Rhizoma Chuanxiong 20 parts, Scorpio 5 parts, Scolopendra 5 parts, Rhizoma Typhonii 10 parts, Rhizoma Et Radix Notopterygii 10 parts, Rhizoma Polygonati 20 parts, the Radix Astragali 20 parts, Rhizoma Curculiginis 10 parts, Herba Epimedii 10 parts, 5 parts of Radix Glycyrrhizae.
Preparation technology:
(1) Scorpio, Scolopendra in prescription are ground into fine powder, cross 80 mesh sieves, standby；
(2) remaining all medicine boiling 2 times, merging filtrate, when being concentrated into 1:1, put and be cooled to room temperature in container, adds ethanol and makes Alcohol content reaches 60%, stands more than 12 hours, reclaims ethanol, is condensed into extractum, and when 20 DEG C, proportion 1.18, standby.
(3) extractum is mixed with fine powder, stir, by 70% ethanol regulation humidity, make soft material, pelletize, dry, whole Grain, subpackage, 15g/ bag.
(4) quality examination, subpackage.
Usage and dosage: 15g/ time, takes after mixing it with water by 3 times/day.It within 10 days, it is 1 course for the treatment of.
Embodiment 2, the preparation of capsule
Proportioning raw materials: in parts by weight
Radix Angelicae Sinensis 40 parts, Rhizoma Chuanxiong 15 parts, Scorpio 3 parts, Scolopendra 3 parts, Rhizoma Typhonii 6 parts, Rhizoma Et Radix Notopterygii 6 parts, Rhizoma Polygonati 15 parts, the Radix Astragali 15 parts, celestial 6 parts of thatch, Herba Epimedii 6 parts, 3 parts of Radix Glycyrrhizae.
(1) Scorpio, Scolopendra in prescription are ground into fine powder, cross 80 mesh sieves, standby；
(2) remaining all medicine boiling 2 times, merging filtrate, when being concentrated into 1:1, put and be cooled to room temperature in container, adds ethanol and makes Alcohol content reaches 60%, stands more than 12 hours, reclaims ethanol, is condensed into extractum, and when 20 DEG C, proportion 1.18, standby;.
(3) extractum is mixed with fine powder, stir, by 70% ethanol regulation humidity, make soft material, pelletize, dry, whole After Li standby；
(4) subpackage: be placed on capsule filling machine and be packed as 0.5g/ grain.1g is equivalent to crude drug 10g；
(5) polishing, quality examination, subpackage.
Usage and dosage: 8 tablets/time, takes after mixing it with water by 3 times/day.It within 10 days, it is 1 course for the treatment of.
Embodiment 3, the preparation of tablet
Proportioning raw materials: in parts by weight
Radix Angelicae Sinensis 50 parts, Rhizoma Chuanxiong 25 parts, Scorpio 8 parts, Scolopendra 8 parts, Rhizoma Typhonii 12 parts, Rhizoma Et Radix Notopterygii 12 parts, Rhizoma Polygonati 22 parts, the Radix Astragali 22 parts, Rhizoma Curculiginis 12 parts, Herba Epimedii 12 parts, 8 parts of Radix Glycyrrhizae.
Preparation technology:
(1) Scorpio, Scolopendra in prescription are ground into fine powder, cross 80 mesh sieves, standby；
(2) remaining all medicine boiling 2 times, merging filtrate, when being concentrated into 1:1, put and be cooled to room temperature in container, adds ethanol and makes Alcohol content reaches 60%, stands more than 12 hours, reclaims ethanol, is condensed into extractum, and when 20 DEG C, proportion 1.18, standby.
(3) extractum is mixed with fine powder, stir, by 70% ethanol regulation humidity, make soft material, pelletize, dry, whole After Li standby；
(4) tabletting: add a certain amount of magnesium stearate and micropowder silica gel, loads tabletting machine, and making every weight is 0.5g；
(5) quality examination, packaging.
Usage and dosage: 8-10 piece/times, takes after mixing it with water by 3 times/day.It within 10 days, it is 1 course for the treatment of.
Embodiment 4, the preparation of drop pill
Proportioning raw materials: in parts by weight
Radix Angelicae Sinensis 43 parts, Rhizoma Chuanxiong 18 parts, Scorpio 5 parts, Scolopendra 5 parts, Rhizoma Typhonii 8 parts, Rhizoma Et Radix Notopterygii 8 parts, Rhizoma Polygonati 18 parts, the Radix Astragali 18 parts, celestial 8 parts of thatch, Herba Epimedii 8 parts, 5 parts of Radix Glycyrrhizae.
Preparation technology:
(1) Scorpio, Scolopendra in prescription are ground into fine powder, cross 80 mesh sieves, standby；
(2) remaining all medicine boiling 2 times, merging filtrate, when being concentrated into 1:1, put and be cooled to room temperature in container, adds ethanol and makes Alcohol content reaches 60%, stands more than 12 hours, reclaims ethanol, is condensed into extractum, and when 20 DEG C, proportion 1.18, standby.
(3) medicine mixes with substrate: add in Macrogol 3000 by fine drug powder and extractum, heats mix homogeneously, standby With；
(4) dripping: choose water-insoluble condensed fluid, adds medicine in pill dripping machine with condensed fluid with substrate, carries out dripping.Every ball It is heavily 0.25g；
(5) cool down, wash ball, select ball；
(6) quality examination, packaging.
Usage and dosage: 16 tablets/time, takes after mixing it with water by 3 times/day.It within 10 days, it is 1 course for the treatment of.
Embodiment 5, soft by the preparation of wafer
Proportioning raw materials: in parts by weight
Radix Angelicae Sinensis 47 parts, Rhizoma Chuanxiong 22 parts, Scorpio 6 parts, Scolopendra 6 parts, Rhizoma Typhonii 10 parts, Rhizoma Et Radix Notopterygii 10 parts, Rhizoma Polygonati 20 parts, the Radix Astragali 20 parts, Rhizoma Curculiginis 10 parts, Herba Epimedii 10 parts, 8 parts of Radix Glycyrrhizae.
Scorpio, Scolopendra in prescription are ground into fine powder by preparation technology (1), cross 200 mesh sieves, standby；
(2) remaining all medicine boiling 2 times, merging filtrate, when being concentrated into 1:1, put and be cooled to room temperature in container, adds ethanol and makes Alcohol content reaches 60%, stands more than 12 hours, reclaims ethanol, is condensed into extractum, and when 20 DEG C, proportion 1.18, standby.
(3) being dried: be placed in microwave dryer by extractum and be dried, crushed after being dried, cross 200 mesh sieves, medicine is thin with pulverizing Powder mix homogeneously, standby；
(4) medicated powder mixes with substrate: powder of getting it filled adds in soybean oil, fully mixes, and medicated powder and soybean oil ratio are 0.5:1.Add Enter a certain amount of wetting agent, suspensoid, after fluidizer, standby；
(5) pelletize: the medicine of mixing and substrate are placed in encapsulating machine, pelletize, every weight 0.5g；
(6) quality examination, packaging.
Usage and dosage: 16 tablets/time, takes after mixing it with water by 3 times/day.It within 10 days, it is 1 course for the treatment of.

Claims (5)

1., for treating the Chinese medicine preparation of idiopathic facial palsy, it is with Radix Angelicae Sinensis, Rhizoma Chuanxiong, Scorpio, Scolopendra, Rhizoma Typhonii, Rhizoma Et Radix Notopterygii, Rhizoma Polygonati, the Radix Astragali, Rhizoma Curculiginis, Herba Epimedii, Radix Glycyrrhizae is crude drug, and common process and adjuvant according to pharmacy of Chinese materia medica are prepared as Oral preparations.
A kind of Chinese medicine preparation for treating idiopathic facial palsy, it is characterised in that: each raw material Proportioning is carried out by following weight portion:
Radix Angelicae Sinensis 40-50 part, Rhizoma Chuanxiong 15-25 part, Scorpio 3-8 part, Scolopendra 3-8 part, Rhizoma Typhonii 6-12 part, Rhizoma Et Radix Notopterygii 6-12 part, Rhizoma Polygonati 15-22 part, Radix Astragali 15-22 part, Rhizoma Curculiginis 6-12 part, Herba Epimedii 6-12 part, Radix Glycyrrhizae 3-8 part.
A kind of Chinese medicine preparation for treating idiopathic facial palsy, it is characterised in that: each raw material Proportioning is carried out by following weight portion:
Radix Angelicae Sinensis 43-47 part, Rhizoma Chuanxiong 18-22 part, Scorpio 5-6 part, Scolopendra 5-6 part, Rhizoma Typhonii 8-10 part, Rhizoma Et Radix Notopterygii 8-10 part, Rhizoma Polygonati 18-20 part, Radix Astragali 18-20 part, Rhizoma Curculiginis 8-10 part, Herba Epimedii 8-10 part, Radix Glycyrrhizae 5-8 part.
A kind of Chinese medicine preparation for treating idiopathic facial palsy, it is characterised in that: each raw material Proportioning is carried out by following weight portion:
Radix Angelicae Sinensis 45 parts, Rhizoma Chuanxiong 20 parts, Scorpio 5 parts, Scolopendra 5 parts, Rhizoma Typhonii 10 parts, Rhizoma Et Radix Notopterygii 10 parts, Rhizoma Polygonati 20 parts, the Radix Astragali 20 parts, Rhizoma Curculiginis 10 parts, Herba Epimedii 10 parts, 5 parts of Radix Glycyrrhizae.
A kind of Chinese medicine preparation for treating idiopathic facial palsy, it is characterised in that: in described Formulation is capsule, granule, tablet, pill.
CN201610782582.2A 2016-08-31 2016-08-31 It is a kind of for treating the Chinese materia medica preparation of bell paralysis Active CN106177446B (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1340350A (en) * 2000-08-26 2002-03-20 甘肃省中医院 Chewing medicine for treating facial paralysis and its preparing process
CN101549119A (en) * 2008-04-03 2009-10-07 北京中科仁和科技有限公司 Pharmaceutical composition for treating idiopathic facial palsy
CN103393863A (en) * 2013-08-14 2013-11-20 河南中医学院 Traditional Chinese medicine for treating peripheral facial paralysis

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1340350A (en) * 2000-08-26 2002-03-20 甘肃省中医院 Chewing medicine for treating facial paralysis and its preparing process
CN101549119A (en) * 2008-04-03 2009-10-07 北京中科仁和科技有限公司 Pharmaceutical composition for treating idiopathic facial palsy
CN103393863A (en) * 2013-08-14 2013-11-20 河南中医学院 Traditional Chinese medicine for treating peripheral facial paralysis

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
周毓萍等: "祛风颗粒治疗特发性面神经麻痹78例", 《西部中医药》 *
窦友义等: "祛风颗粒治疗特发性面神经麻痹78例", 《中国中医药信息杂志》 *

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