CN101468082A - Gel patch for treating facial paralysis and preparation method thereof - Google Patents

Gel patch for treating facial paralysis and preparation method thereof Download PDF

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Publication number
CN101468082A
CN101468082A CNA200710060468XA CN200710060468A CN101468082A CN 101468082 A CN101468082 A CN 101468082A CN A200710060468X A CNA200710060468X A CN A200710060468XA CN 200710060468 A CN200710060468 A CN 200710060468A CN 101468082 A CN101468082 A CN 101468082A
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gel
preparation
facial paralysis
treatment
medicine
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高惠明
李扬
方昊
周英超
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Tianjin Zhongbao Pharmaceutical Co Ltd
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Tianjin Zhongbao Pharmaceutical Co Ltd
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Priority to CNA200710060468XA priority Critical patent/CN101468082A/en
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Abstract

The present invention relates to a traditional Chinese medicine gel plaster for treating facial paralysis and its preparation method, composed of 5%-50% of extract of traditional Chinese medicine and 95%-5% of medicinal adjuvant. The traditional Chinese medicine plaster is prepared by mixing the molecule gel, the hydrogel, active ingredients of medicine extracts with the plural gel factor. Different medicine extracts enter into the skin through different channels. The oil-soluble component in molecule gel has repulsion force to the water-soluble medicine and the water-soluble component in hydrogel has repulsion force to the oil-soluble medicine therefore the medicine absorption is promoted and the medicine efficacy is increased.

Description

A kind of gel adhesive for the treatment of facial paralysis and preparation method thereof
Technical field
The present invention relates to the up-to-date molecular gel of Percutaneously administrable preparation technical field combines with hydrogel and makes profit ampholytic gels patch, adopt mixing active ingredients thing that Radix Achyranthis Bidentatae, Fructus Chaenomelis, Caulis Spatholobi, Mel four flavor Chinese medicine compositions extract for the basis in addition the medicinal substrate preparation have treatment facial paralysis Transdermal absorption gel adhesive and preparation method thereof, specifically be a kind of Chinese medicine profit ampholytic gels patch for the treatment of facial paralysis.
Background technology
Transdermal drug delivery system or percutaneous absorption patch refer to stick the mode medication through skin, and medicine enters the systemic blood circulation by skin absorbs and reaches a class preparation of effective blood drug concentration, realization disease treatment or prevention.The characteristics of percutaneous absorption patch are, transdermal drug delivery system can avoid the first pass effect of liver and medicine in the gastrointestinal deactivation, the absorption of medicine is not subjected to the influence of gastrointestinal factors, reduce the individual variation of medication, keep constant effective blood drug concentration or physiological effect, the blood drug level peak valley phenomenon of avoiding oral administration to cause reduces toxicity.Reduce administration number of times, improve therapeutic efficacy, prolong action time, avoid multiple dose administration, make most patient be easy to accept, simultaneously easy to use, independently medication of patient also can be cancelled medication at any time.
So-called profit ampholytic gels is not the zwitterion that we say usually, because molecular gel generally all is as solvent by oil-based solvent, organic solvent or the mixture of the two, it is gel with oleophilic properties, and used aqueous solvent accounts for greatly in the hydrogel, it is the gel of possess hydrophilic property matter, the two is used, so be called the profit ampholytic gels.
Molecular gel is that the gel factor (some micromolecule organic compound) is passed through non-covalent interaction in non-aqueous media, spontaneously assembles, assembles orderly three-dimensional fiber network structure, makes the medium gelation.Molecular gel has reversible characteristics of heat, and processing technology is simple, and gelinite contains a large amount of organic solvents, be fit to the storage storehouse as lipophilic medicament, but molecular gel exists cohesiveness low, and viscosity is little, with the skin poor compliance, is not suitable for making shortcomings such as patch.Hydrogel water content height is fit to the storage storehouse as hydrophilic medicament, and is strong to the skin compliance, but is subjected to the influence of self property, and colloid poor plasticity, elasticity are little.In sum, be advantage in conjunction with these two kinds of gels, adopt the pluralgel factor that two kinds of gelinites are disperseed mixing, with the molecular gel is framework material, the patch substrate that hydrogel is made as sticky stuff, both high resilience forms have good compliance with skin, can peel off repeatedly, paste again, improve the drug loading of hydrophilic medicament and hydrophobic drug simultaneously again.Two kinds of gels twine staggered uniform distribution in substrate, by non-covalent bond form combinations such as Van der Waals forces, by fully contacting with skin, the both sexes medicine continues to see through skin through passage separately, enters blood circulation, the performance drug effect.
Facial paralysis (facial neuritis, bell's palsy, hunter syndrome), be commonly called as " facial paralysis ", " wapperijaw crust " " wapperijaw ", " facial paralysis ", " hang skew wind ", " facial neuritis ", " wapperijaw wind " etc., be to be a kind of commonly encountered diseases of principal character with facial expression muscle group dyskinesia, its cardinal symptom is facial expression muscle functional defect or forfeiture, cause distortion of commissure, hypophasis, facial expression is stiff, language inconvenience, food is detained in the Ipsilateral bicker, even Ipsilateral corneal clouding, blind, cause ugly face, give patient's life, the worker does with social activity and brings very big difficulty, make the patient lose the confidence and the courage of participating in society, in addition overwhelmed with sorrow.It is a kind of commonly encountered diseases, frequently-occurring disease, and it is not subjected to age limit.Facial paralysis is divided on every side two kinds of property and central.Wherein the peripheral facial paralysis sickness rate is very high, and the most common person is facial neuritis or Bell's palsy.The normal facial paralysis of saying of usual people institute is meant facial neuritis as a rule.
The treatment of facial paralysis, central paralysis should be at the cause of disease, and paralysis peripherica should take appropriate measures according to the morning and evening of the course of disease.The early treatment of paralysis peripherica, purpose is to manage to recover the function of nerve, and method comprises: acupuncture, decompression, nerve anastomosis, neural transplantation or nerve cross anastomosis and neural Coronary Artery Bypass etc.The anaphase of paralysis peripherica, purpose are to manage to correct deformity and improve function, be used for after early stage treatment, often between with examining observation, recover dissatisfied, or confirm the case of recovering hopeless.The later stage plastic operation has static(al) support and power to support two kinds of methods, the degree of deformity severe patient, and still needing cooperates complementary operation, to heighten the effect of a treatment.
Treatment for facial paralysis, on Western medicine, do not have reasonable medicine now, great majority are just started with from uncomfortable symptom such as the pain of reduction of patient, can not treat its basic effective medicine, and clinical treatment means treatments such as acupuncture, massage are adopted in treatment by Chinese herbs mostly.The treatment of facial paralysis is long the course of treatment, and medical expense is relatively more expensive, is difficult for being accepted by masses, and now, the treatment facial paralysis is the reasonable treatment preparation of neither one also.
Summary of the invention
The vacancy that the present invention can remedy on the market can satisfy popular demand again, has avoided the oral formulations uncertain therapeutic efficacy and has cut, and it is frequent easily to be inactivated in gastrointestinal and to take medicine, shortcomings such as inconvenience.The invention provides a kind of, release remarkable and easy to use to treatment facial paralysis effect slowly steadily, to little Chinese medicine composition Transdermal absorption profit ampholytic gels patch of skin irritation and preparation method thereof.This gel has the strong and high resilience of cohesiveness, and is good with the skin adhesion, can peel off multiple subsides repeatedly; Water content is big, and is strong with the skin compliance, can improve the permeability of skin, helps the Transdermal absorption of medicine; Preparation is simple, is beneficial to industrialized great production.
This prescription Radix Achyranthis Bidentatae has promoting blood circulation to restore menstrual flow, invigorating the liver and kidney, bone and muscle strengthening, relieving stranguria by diuresis, (blood) the descending effect of igniting; Fructus Chaenomelis has relaxing muscles and tendons and activating QI and blood in the collateral, the effect of dehumidifying stomach function regulating; Caulis Spatholobi has promoting the circulation of blood to enrich blood, regulating menstruation, the effect of relaxing muscles and tendons and activating QI and blood in the collateral; Mel invigorating middle warmer emergency is moisturized, the antidotal effect; All medicines are harmonious, and reach the effect of treatment facial paralysis by promoting blood circulation to remove obstruction in the collateral, the detoxifcation of enriching blood.
The technical solution used in the present invention is: a kind of Chinese medicine composition profit ampholytic gels patch for the treatment of facial paralysis and preparation method thereof; it is made up of backing layer, adhesive-layer, protective layer, it is characterized in that the adhesive-layer in this patch mainly is made up of medicine, profit ampholytic gels and short penetrating agent.Said preparation is made up of following medicaments in part by weight extract, wherein, and Radix Achyranthis Bidentatae 3-30, Fructus Chaenomelis 5-30, Caulis Spatholobi 5-35, Mel 5-45; The weight part ratio of adhesive-layer Chinese medicine effective ingredient and profit ampholytic gels (molecular gel: hydrogel is 1:1-10) is 1:1-25.Transdermal enhancer 3-8 weight portions, the weight percent content of the effective ingredient of Chinese medicine mixture is 5%-50% in the gel adhesive.Transdermal penetration agent, effective ingredient extract, molecular gel and hydrogel add with order respectively in proportion, and mix homogeneously is uniformly coated on the backing layer, the compound protective layer of going up, and after the extrusion modling, sterilization, stamping-out are made product.
Described drug molecule gel can be made as follows: 1%-30% gel factor is dissolved in the mixture of specific organic solvent or organic solvent.Medicine is dissolved in the organic solvent, adds a certain amount of gel factor then and mix, promptly get molecular gel.The gel factor that is adopted is divided into two classes, the first kind is simple tertiary amine and quaternary ammonium salt thereof such as lecithin, N, N, the two octadecane amine of N-three-octadecane amine, gallbladder steroid eicosane amine, methyl, dioctadecyl dimethyl ammonium chloride and cyclodextrin derivative class as: organic molecules such as beta-schardinger dextrin-, second class are derivative of fatty acid as 12-hydroxy octadecadienoic acid and associated salts thereof, glyceryl monostearate, glyceryl tristearate, tripalmitin etc.Organic solvent comprises alkanes, arene, dimethyl sulfoxide (DMSO), acetonitrile, 1-propanol, 1-amylalcohol, 1-capryl alcohol, propylene glycol, glycerol, silicone oil, 14/isopropyl palmitate etc.
Described medicine hydrogel can be made as follows:
The first kind, 2%-15% sodium polyacrylate, 1%-30%PVP and 1%-20%CMC-Na pressed powder mix homogeneously are scattered in 15%-60% propylene glycol, the glycerol solvent, and mix homogeneously adds 40%-80% deionized water mix homogeneously promptly.The 0%-15% additive, additive comprises: Kaolin, starch, micropowder silica gel, aluminum chloride, Alumen, sodium alginate etc.
Second class, 0.1%-10% carbomer, 1%-20% sodium polyacrylate, 15%-40% glycerol, 30%-80% propylene glycol, 3%-15% ethanol, 5%-20% additive, additive comprises: Kaolin, starch, micropowder silica gel, citric acid, citric acid, ethanol, aluminum chloride, triethanolamine, ethyl hydroxybenzoate, ammonium stearate, disodium EDTA (EDTA-2Na), sodium benzoate, parabens or the like.
The above-mentioned described first kind prescription gel factor can only cooperate with first kind gel, and the second gellike factor and the second gellike agent cooperate.Because the fundamental property of two gellikes is different, intersection is combined with change or the chemical reaction that framework may take place.
Penetrating agent of the present invention comprises dimethyl sulfoxide and analog: dimethyl sulfoxide (DMSO); Azone compounds: laurocapram Azone; Alcohol compound: ethanol, propylene glycol, glycerol; Volatile oil and or their mixture etc.Described backing layer is non-woven fabrics or polyester film, and protective layer is paper or polyester film through release treatment.
Chinese crude drug extraction process of the present invention is not limited to aqueous extraction-alcohol precipitation technology, also can be that water is put forward other extraction processes such as organic solvent extractionprocess, alcohol extraction organic solvent extractionprocess and supercritical fluid extraction; Coating processes such as the also available blade coating molding of the preparation technology of patch.Gel adhesive of the present invention can be made arbitrary shape.
Process conditions:
A. extract drugs technology
(a) get a certain amount of Chinese medicine Radix Achyranthis Bidentatae, use 50-100% alcohol reflux 3 times, with 4 times of amount alcohol, extract 60min for the first time, with 3 times of amount alcohol, extract 60min for the second time, use the alcohol of 2 times of amounts for the third time, extract 30min, filter, merging filtrate, concentrating under reduced pressure is to heavy-gravity extractum, and is standby.
(b) get a certain amount of Chinese medicine Caulis Spatholobi, drying and crushing, press solid-to-liquid ratio 1 with 50-100% ethanol and 1-12% hydrochloric acid mixed solution: 2-20 reflux, extract, three times, filter, merging filtrate, filtrate is used NaHCO 3Neutralization (pH=4.0-6.0), filtrate decompression are steamed and removed ethanol and reclaim solvent, get the Caulis Spatholobi crude extract, and be standby.
(c) get a certain amount of Fructus Chaenomelis, pulverize, add the 50%-100% ethanol that 3-12 doubly measures, 40-80 ℃ of reflux, extract, three times, each 2h, merge extractive liquid,, reclaim under reduced pressure is concentrated into 20-300ml, and is standby.
B. the preparation technology of patch:
(a) preparing process of profit ampholytic gels:
The first kind: get a certain amount of sodium polyacrylate, PVP and CMC-Na pressed powder and add in the agitator, heat 20-90 ℃, be scattered in propylene glycol, the glycerol solvent, mix homogeneously, after adding molecular gel required organic solvent and drug extract mixing behind the adding deionized water mix homogeneously, after slowly mixing after the adding mixed gel factor, progressively lower the temperature, form the profit ampholytic gels until room temperature.
Second class: get in a certain amount of carbomer, sodium polyacrylate, glycerol, propylene glycol, ethanol, the additive adding agitator, heat 20-90 ℃, behind the mix homogeneously, add required organic solvent and the drug extract mixing of molecular gel, after slowly mixing after the adding mixed gel factor, progressively lower the temperature until room temperature, form the profit ampholytic gels.
(b) preparation technology of paster
The drug matrices that is mixed is evenly coated on the backing layer non-woven fabrics, will covers on the medicine glue-line through the polyester protecting film that release treatment is crossed, enter the roller bearing extrusion modling, THICKNESS CONTROL is below 5mm.Stamping-out, screening, quality inspection, packing are carried out by specification in the sterilization back.
(c) profit ampholytic gels patch application characteristic:
Respectively to hydrogel adhesive, oil-base gel agent, molecular gel agent, four kinds of gels of ampholytic gels patch from mouldability, first viscous force, peeling force, tough elastic force, seven performance indications of compliance of skin irritation, preparation stability, patient are investigated.Every definition standard is as follows.
Mouldability: four kinds of gels of equal in quality are coated on the non-woven fabrics uniformly the overall appearance of observing colloid, loosely organized degree.
First viscous force: the assay method according to the first viscous force of patch in (2005) second appendix XJ patches of Chinese Pharmacopoeia adhesive force algoscopy is measured comparison to four kinds of gels that are coated on the non-woven fabrics.
Peeling force: the assay method according to peel strength in (2005) second appendix XJ patches of Chinese Pharmacopoeia adhesive force algoscopy is measured comparison to four kinds of gels that are coated on the non-woven fabrics.
Tough elasticity: coating on the non-woven fabrics circular glass sheet of placing identical size on four kinds of gel-type vehicles, a 20g counterweight is put by sheet central authorities, after the pressure relief, observes gel shape recovery situation and compares.
Skin irritation: observe animal intact skin single and repeatedly contact gel the local excitation reaction that is produced.(300g ± 20g), male and female half and half are divided into 8 groups, 5-6 every group to choose healthy albino guinea-pig.24h is with Cavia porcellus spinal column both sides unhairing before administration, check whether skin of unhairing has wound, apply ointment or plaster in the left and right sides of every Cavia porcellus the respectively gel of same dose is observed single-dose and is removed the situation that erythema and edema appear in skin in 1h, 24h behind the gel, 48h, the 72h.Repeatedly apply ointment or plaster more than the week, observe again a week after stopping, the redness of observed and recorded skin every day and edema situation and smear the position whether pigmentation, situation such as hemorrhage are arranged.Stability: placed at ambient temperature 1 month, the character of observing each gel changes situation.
Patient's compliance: select some normal adults, stick four kinds of gels respectively, compare from situations such as the sensation of skin, degree easy to use.
Four kinds of various performance comparison results of gel
Figure A200710060468D00101
Annotate: +++for well; ++ in; + for poor
The specific embodiment
Below example by the specific embodiment, foregoing of the present invention is described in further detail, embodiment only is indicative, means that never it limits the scope of the invention by any way.But do not breaking away under the above-mentioned technological thought situation of the present invention, the various replacements of making according to ordinary skill knowledge and habitual means or the modification of change include within the scope of the invention.
Embodiment 1:
Transdermal enhancer laurocapram Azone 3.5kg
Molecular gel 2.5% lecithin,
97.5% Semen Myristicae isopropyl ester 100kg
Hydrogel 8% sodium polyacrylate, 2% polyvinylpyrrolidone
2% sodium carboxymethyl cellulose, 20% propylene glycol
20% glycerol, 48% deionized water 400kg
Effective ingredient mixture 75kg
Take by weighing 32kg sodium polyacrylate, 8kg polyvinylpyrrolidone and 8kg sodium carboxymethyl cellulose pressed powder mix homogeneously, be scattered in 80kg propylene glycol, the 80kg glycerol solvent, mix homogeneously in agitator adds the 192L deionized water, mix homogeneously, get 97.5kg Semen Myristicae isopropyl ester and place agitator, add 75Kg effective ingredient mixture, containing the Radix Achyranthis Bidentatae extract weight portion in the mixture is 20kg, Fructus Chaenomelis 15kg, Caulis Spatholobi 20kg, Mel 25kg.Add the 3.5Kg laurocapram, 60 ℃ of heated and stirred add 2.5Kg lecithin to mixings fully, after slowly stirring with 100 rev/mins, cooling, temperature reduce to stop to stir after the room temperature leave standstill 5h gel.The drug gel substrate that is mixed is evenly sprayed cloth on the backing layer non-woven fabrics, will cover on the medicine glue-line through the polyester protecting film that release treatment is crossed, enter the roller bearing extrusion modling, THICKNESS CONTROL is below 5mm.Stamping-out is carried out by specification in the sterilization back, makes patch, and coefficient of losses 15% is pressed Chinese Pharmacopoeia patch standard through quality inspection qualification rate 85%.The certified products packing.
Embodiment 2:
Transdermal enhancer oleic acid 3.5kg
Molecular gel 5% glyceryl monostearate
95% cyclohexane extraction 150kg
Hydrogel 0.5% carbomer, 5% sodium polyacrylate
28.5% propylene glycol, 60% glycerol,
4% ethanol, 1.4% Kaolin,
0.2% citric acid, 0.4% triethanolamine 500kg
Effective ingredient mixture 100kg
Take by weighing 25kg sodium polyacrylate, 2.5kg carbomer pressed powder mix homogeneously, be scattered in 142.5kg propylene glycol, the 300kg glycerol solvent, mix homogeneously in agitator adds 20Kg ethanol, 7Kg Kaolin, 1Kg citric acid, 2Kg triethanolamine, mix homogeneously, get the 142.5kg cyclohexane extraction and place agitator, add 100Kg effective ingredient mixture, containing the Radix Achyranthis Bidentatae extract weight portion in the mixture is 30kg, Fructus Chaenomelis 25kg, Caulis Spatholobi 25kg, Mel 20kg.Add 3.5Kg oleic acid, 60 ℃ of heated and stirred add the 7.5Kg glyceryl monostearate to mixings fully, after slowly stirring with 100 rev/mins, cooling, temperature reduce to stop to stir after the room temperature leave standstill 5h gel.The drug matrices that is mixed is evenly sprayed cloth on the backing layer non-woven fabrics, will cover on the medicine glue-line through the polyester protecting film that release treatment is crossed, enter the roller bearing extrusion modling, THICKNESS CONTROL is below 5mm.Stamping-out is carried out by specification in the sterilization back, makes patch, and coefficient of losses 5% is pressed Chinese Pharmacopoeia patch standard through quality inspection qualification rate 95%.The certified products packing.

Claims (7)

1. treat gel adhesive of facial paralysis and preparation method thereof for one kind; it is characterized in that: it is made up of backing layer, adhesive-layer, protective layer; adhesive-layer is mixed and made into by Radix Achyranthis Bidentatae, Fructus Chaenomelis, Caulis Spatholobi, Mel four flavor Chinese medicine effective component extracts and molecular gel, hydrogel, transdermal enhancer; the weight portion proportioning is: effective ingredient extract 10-200 part; 3-8 parts of transdermal enhancers; 100-300 parts of molecular gels, 200-1000 parts of hydrogels.
2. according to described a kind of gel adhesive for the treatment of facial paralysis of claim 1 and preparation method thereof, it is characterized in that: described molecular gel is formed and percentage by weight is: the gel factor 1%-30%, solvent or their mixture 50%-90%.The gel factor comprises the tertiary amine of ad hoc structure and quaternary amines organic compound thereof such as lecithin, N, N, N-three-octadecane amine, gallbladder steroid eicosane amine, the two octadecane amine of methyl, dioctadecyl dimethyl ammonium chloride; Organic molecules such as cyclodextrin derivative class such as beta-schardinger dextrin-; Derivative of fatty acid such as 12-hydroxy octadecadienoic acid and associated salts thereof, glyceryl monostearate, glyceryl tristearate, tripalmitin etc.Solvent comprises alkanes, arene, dimethyl sulfoxide (DMSO), acetonitrile, 2-ethoxy ethanol, 1-propanol, 1-amylalcohol, 1-capryl alcohol, 1,2-propylene glycol, glycerol, silicone oil, 14/isopropyl palmitate etc.
3. according to described a kind of gel adhesive for the treatment of facial paralysis of claim 1 and preparation method thereof, it is characterized in that: the composition of described hydrogel and percentage by weight are water-soluble base, water-insoluble substrate or their mixture 5%-30%, solvent 50%-90%, additive 1%-10%.Water-soluble base and non-aqueous substrate comprise polypropylene acid, sodium polyacrylate, carbomer resin, polyvinylpyrrolidone, sodium carboxymethyl cellulose, methylcellulose, polyvinyl alcohol and/or their mixture of various models; Additive comprises Kaolin, starch, micropowder silica gel, aluminum chloride, Alumen, sodium alginate etc.; Solvent comprises deionized water, propylene glycol, glycerol, ethanol and/or their mixture.
4. according to described a kind of gel adhesive for the treatment of facial paralysis of claim 1 and preparation method thereof, it is characterized in that: described penetrating agent comprises dimethyl sulfoxide and analog, azone class, alcohol compound, volatile oil and/or their mixture.
5. according to described a kind of gel adhesive for the treatment of facial paralysis of claim 1 and preparation method thereof, it is characterized in that: described backing layer is non-woven fabrics or polyester film, and protective layer is paper or polyester film through release treatment.
6. according to described a kind of gel adhesive for the treatment of facial paralysis of claim 1 and preparation method thereof, it is characterized in that: described preparation process comprises:
Getting the required organic solvent of the required mixture of a certain amount of preparation hydrogel, solvent, deionized water and preparation molecular gel adds in the agitator, heat 20-90 ℃, after mixing, add the abundant mixing of effective ingredient extract, after slowly mixing after the adding mixed gel factor, progressively lower the temperature until room temperature, form the profit ampholytic gels.
7. according to described a kind of gel adhesive for the treatment of facial paralysis of claim 1 and preparation method thereof, it is characterized in that: preparation technology is spreading formation process, extrusion modling or spray mo(u)lding technology.
CNA200710060468XA 2007-12-28 2007-12-28 Gel patch for treating facial paralysis and preparation method thereof Pending CN101468082A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103228255A (en) * 2010-11-30 2013-07-31 株式会社爱茉莉太平洋 Cosmetic composition comprising sodium polyacrylate and water-soluble polymer
CN108815482A (en) * 2018-08-01 2018-11-16 佛山科学技术学院 It is a kind of for treating and preventing the gel combination of facial paralysis

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103228255A (en) * 2010-11-30 2013-07-31 株式会社爱茉莉太平洋 Cosmetic composition comprising sodium polyacrylate and water-soluble polymer
CN103228255B (en) * 2010-11-30 2016-04-13 株式会社爱茉莉太平洋 Cosmetic composition containing sodium polyacrylate and water-soluble polymer
CN108815482A (en) * 2018-08-01 2018-11-16 佛山科学技术学院 It is a kind of for treating and preventing the gel combination of facial paralysis

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