A kind of lignocaine compound preparation and aerosol thereof
Technical field
The invention belongs to field of medicaments, be specifically related to a kind of slight incised wound, scratch, soft tissue injury that can be used for skin, burn and lignocaine compound preparation and the aerosol thereof of the disease such as mosquito bite, pruritus, miliaria.
Background technology
Mosquito bite is dermatosis in a summer major reason occurred frequently.Owing to containing plurality of antigens composition in the saliva of mosquito or the leachate of poison gland, these antigens are entering after human body skin and can produce atopic reaction with antibody and cause inflammation, make patient occur red, the symptom such as swell, itch, when serious, even produce local bulla, hemorrhagic necrosis etc., to bringing inconvenience our orthobiosis.For mosquito bite, scratch and soft tissue injury, it is generally acknowledged debridement treatment as early as possible, prevention infection occurs.The treatment of doctor trained in Western medicine is to be coated with to spread some antipruritic medicines mostly, Western medicine belongs to corticosteroids medicine mostly, while using these medicines, occur a large amount of more serious bad side reactions as there is local aseptic abscess, erythra, hypotension, feel sick, the untoward reaction such as vomiting, dizzy, hypoglycemia, low blood calcium and hepatic and renal function injure.And the treatment of the traditional Chinese medical science is to smear some Chinese medicinal ointments to carry out heat-clearing and toxic substances removing, subside a swelling and alleviate pain, although patient's centering medical instrument has good Drug tolerance, without anaphylaxiss such as erythra, need the long period just can take effect, can not play the effect of Quick itch stopping.In addition, doctor trained in Western medicine or Chinese traditional treatment all should be noted that to keep wound surface dry, clean, but its embrocate medicine and carry and use all inconveniently, easily produce superinfection, and need repeated multiple times embrocating, there is certain zest.
Lignocaine is the local anesthesia that medical and clinical is conventional, has the antipruritic effect that relieves the pain, and also has report to be used for treating some disease of skin aspect.As Bao Yahua discloses a kind of compound lidocaine emulsifiable paste and preparation method thereof in patent CN101816642A, its effective ingredient is mainly lignocaine and prilocaine, solve the technical problem of existing compound lidocaine emulsifiable paste unstable product quality and clinical practice safety, it is very inconvenient that but this cream products is used, and poor effect.In addition, aerosol is owing to having direct arrival site of action, be evenly distributed, stability rapid-action, medicine is high, wound surface zest is little, dosage control is more accurate, can single dose or the feature such as multiple dose administration, convenience easy to carry and use and be subject to people's favor.Aerosol products is of a great variety, can be divided into following Four types according to the formula of product: (1) active component and propellant.(2) active component, solvent and propellant.(3) active component, surfactant and propellant.(4) active component, solvent, surfactant and propellant.State according to aerosol in tank, aerosol products can be divided into again solvent-borne type aerosol, suspension aerosol and dry-type aerosol.Traditional medicinal aerosol is mainly to adopt freon to make propellant, and it can destroy atmospheric ozone layer.And in CN101756901A, in course of injection, easily form fine particle, and affect the absorption of medicine, cause local drug concentration too high and cause untoward reaction because of the nonunf ormity of drug particles simultaneously.
The people such as Cao Longxiang disclose a kind of lignocaine and have determined aerosol in patent CN101785766B, it has good therapeutic effect for mosquito bite and skin injury, reduce the zest to skin, but this aerosol component is many, contain the components such as lignocaine, chlorhexidine acetate, benzalkonium bromide, PVP-VA64, ethyl acetate, active component is not limited only to lignocaine, and this aerosol does not possess repair to skin simultaneously.
In sum, be Western medicine in the market, and comprise multiple Western medicine active component about Lidocaine Aerosol product main active, aerosol products occurs disperseing inhomogeneous after injection, and product can not film forming, external poor effect.
Summary of the invention
The invention provides that a kind of environmental friendliness, physicochemical properties are stable, good dispersion and there is antipruritic, anti-inflammation and sterilization, self-regeneration function, zest to skin is little, can be widely used in skin slight incised wound, abrade, burn, infection, mosquito bite, pruritus, miliaria that sunburn, soft tissue injury cause and when alleviating the symptoms such as local myalgia, arthralgia, wet disease, can fully be conducive to again the lignocaine compound preparation of preparation of dosage form itself.
Another object of the present invention is as solving in the past many for the external Lida-Mantle Western medicine active component of antipruritic, sterilization, antiinflammation, particularly aerosol products very easily forms fine particle after spraying, disperse inhomogeneous, product does not possess film property or film property is not good, can not promote the problems such as the self-regeneration of skin; Provide one can effectively overcome above problem, and the lignocaine compound type aerosol of good film-forming property.
This technical scheme is lignocaine compound preparation, in described compound preparation, also Aloe extract and/or chitosan and Herba Rosmarini Officinalis extract has not only been added as active component but also as inactive ingredients adjuvant; Relative 100 weight portion lignocaine, the addition of Aloe extract and/or chitosan is no more than 5000 weight portions, and the addition of Herba Rosmarini Officinalis extract is no more than 200 weight portions.
Lignocaine compound preparation of the present invention comprises active component and pharmaceutical adjunct, and its active component comprises lignocaine; In this compound preparation, Aloe extract and/or chitosan were both made to both parts as active component, add as the surfactant in inactive ingredients adjuvant and/or dispersant again, simultaneously, Herba Rosmarini Officinalis extract is both as the part of active component, again as the antioxidant in adjuvant and aromatic.
In the present invention, relative 100 weight portion lignocaine, the addition of Aloe extract is no more than 5000 weight portions, preferably be no more than 1500 weight portions, even more preferably be no more than 1000 weight portions, more preferably 10-1000 weight portion, most preferably 200-1000 weight portion.
In the present invention, relative 100 weight portion lignocaine, the addition of chitosan is no more than 5000 weight portions, is preferably no more than 1500 weight portions, is even more preferably no more than 1000 weight portions, more preferably 10-1000 weight portion; Most preferably 200-1000 weight portion.
Relative 100 weight portion lignocaine, the addition of Herba Rosmarini Officinalis extract is no more than 200 weight portions, is preferably no more than 150 weight portions, is even more preferably no more than 100 weight portions, and preferred content is 20-100 weight portion.
The preferred technical scheme of the present invention is, relative 100 weight portion lignocaine, and the addition of Aloe extract and/or chitosan is no more than 1500 weight portions, and the addition of Herba Rosmarini Officinalis extract is no more than 150 weight portions.
The present invention further preferred technical scheme is, relative 100 weight portion lignocaine meters, and Aloe extract content is 10-1000 weight portion, and chitosan content is 10-1000 weight portion, and Herba Rosmarini Officinalis extract content is 20-100 weight portion.
Described lignocaine is selected from the one in lignocaine, Lidocaine base, lidocaine hydrochloride or lidocaine carbonate.Described Aloe extract comprises one or more in effective ingredient Aloe resin B, aloe-emodin, aloin.
The molecular weight of described chitosan is 200-800.
Described lignocaine compound preparation is Lidocaine Aerosol.
This aerosol also further comprises propellant and solvent.
Described propellant is selected from one or more in isceon, dichlorodifluoromethane, Dichlorotetrafluoromethane, propane, tetrafluoroethane, heptafluoro-propane, normal butane, iso-butane, dimethyl ether.Described solvent is selected from one or more in ethanol, ethyl acetate, propylene glycol.
Addition to described solvent is not particularly limited, as long as can be by various components dissolved.Preparation total amount relatively, its consumption is preferably 0.5-50 % by weight, preferably 1-25 % by weight, more preferably 1-10 % by weight.
In the gross weight of described aerosol, the content of propellant is not less than 50%.
In the gross weight of described aerosol, the content of propellant is 50-99.999 % by weight, preferably 60-99.995 % by weight, and more preferably 70-99.99 % by weight, is preferably 80-99 % by weight.
The optimal technical scheme of aerosol of the present invention is: described propellant is the combination of a kind of and n-propane in isceon, heptafluoro-propane, and its weight proportion is 1:99-99:1, and preferably 10:90-90:10, is preferably 15:85-85:15.
In aerosol of the present invention, further also comprise wetting agent, described wetting agent is selected from one or both in glycerol, propylene glycol, mineral oil, vegetable oil.
Concrete Lidocaine Aerosol formula for a product of the present invention comprises active component, solvent and propellant.The active component of this formula comprises lignocaine, Aloe extract and/or chitosan, Herba Rosmarini Officinalis extract.Wherein the lignocaine in formula plays the effect of antipruritic pain relieving, is one of main active component.Aloe extract plays sterilization, antiinflammatory, reparation and is injured damaged function of organization.Chitosan plays the anti-infection of sterilization and the effect at skin surface film forming and then promotion wound healing.Herba Rosmarini Officinalis plays antioxidation and antiseptical effect.Aloe extract and/or chitosan are except playing the effect of active component, and it has good peptizaiton to lignocaine.In the process of ejecta atomization, lignocaine isoreactivity component is disperseed very even in Aloe extract/chitosan, under the condition without additional dispersant and/or surfactant, can make the aerosol ejecting be uniformly dispersed and easy film forming at skin surface, effectively promote the absorption of medicine.Herba Rosmarini Officinalis extract is except playing the effect of anti-inflammation and sterilization, and it also has antioxidative effect, can effectively ensure Lidocaine Aerosol steady quality.Solvent plays the dissolubility effect that increases active component, promotes each component mix homogeneously.
The preparation method of this Lidocaine Aerosol is first by even to active component and solvent, then its mixture is filtered and is filled in aerosol aluminium pot, and sealing-in aerosol pump, is finally pressed into propellant and get final product.
Except being prepared into Lidocaine Aerosol, the present invention can also add other preparation and pharmaceutically acceptable adjuvant thereof, make and comprise above-mentioned active component lignocaine, and Aloe extract and/or chitosan, Herba Rosmarini Officinalis extract are at other preparation types such as interior spray, water smoke agent, unguentum or suppositorys.Above-mentioned dosage form can prepare by conventional method, and can on the basis of above-mentioned active component, add other additive and auxiliary material.
Compound preparation of the present invention, can be according to the needs of production of compound preparation in the time being prepared into corresponding preparations type, further adds active constituents of medicine acceptable carrier adjuvant of the present invention.Described active constituents of medicine acceptable carrier is selected from other antioxidant, surfactant, dispersant, lubricant, solvent slow release material etc.Conventional carrier comprises cellulose and cellulose derivative, polyvinylpyrrolidone etc.
The present invention is compared with Lida-Mantle of the prior art, and Lida-Mantle of the present invention is Chinese medicine and western medicine compound preparation, and its active component comprises lignocaine, Aloe extract and/or chitosan, Herba Rosmarini Officinalis extract.Wherein, Aloe extract and/or chitosan are both as the part of active component, add as inactive ingredients adjuvant again, conventional surfactant and/or dispersant are substituted, it has good peptizaiton to lignocaine, give the film property function that product is good simultaneously, effectively promoted the absorption of medicine.In addition, Herba Rosmarini Officinalis extract both, as a part for active component, added as inactive ingredients adjuvant again, had substituted conventional antioxidant and aromatic, had strengthened the stability of product.The present invention can, not needing to add on the basis of other surfactant and dispersant, still have stable physicochemical properties.Preparation of the present invention is containing chlorine fluorine alkane not, environmental friendliness.The present invention is different from the different dosage form that the composition of prior art the obtains physicochemical properties of Lida-Mantle by preparation are stable, good dispersion, good film-forming property, there is antipruritic, anti-inflammation and sterilization, self-regeneration function, zest to skin is little, can be widely used in skin slight incised wound, abrade, burn, infection, mosquito bite, pruritus, miliaria that sunburn, soft tissue injury cause and alleviate the symptoms such as local myalgia, arthralgia, wet disease, film property, the dispersibility of the aerosol particularly preparing are good especially, and drug effect is fast.
Detailed description of the invention
Further describe the present invention below in conjunction with embodiment, but the scope of this area is not limited to this.Wherein, because the effect of the preparation of different dosage form is similar, and the preparation method of different preparations is all known, therefore, in an embodiment only taking Lidocaine Aerosol as representative, is used for illustrating the effect that the present invention can obtain.
Embodiment 1
The consumption of each component is:
Preparation method: above-mentioned lignocaine, Aloe extract, Herba Rosmarini Officinalis extract through powdered is fully dissolved in 3g dehydrated alcohol, again this settled solution is transferred in aerosol aluminium pot, sealing-in aerosol pump, is pressed into 25.25g propellant tetrafluoroethane, obtains stable medicinal aerosol.
Embodiment 2
The consumption of each component is:
Preparation method: above-mentioned lignocaine, Aloe extract, Herba Rosmarini Officinalis extract through powdered is fully dissolved in 3g dehydrated alcohol, again this settled solution is transferred in aerosol aluminium pot, sealing-in aerosol pump, is pressed into 23.75g propellant tetrafluoroethane, obtains stable medicinal aerosol.
Embodiment 3
The consumption of each component is:
Preparation method: above-mentioned lignocaine, chitosan, Herba Rosmarini Officinalis extract through powdered is fully dissolved in 3g dehydrated alcohol, settled solution is transferred in aerosol aluminium pot, sealing-in aerosol pump, is pressed into 23.75g propellant tetrafluoroethane, obtains stable medicinal aerosol.
Embodiment 4
The consumption of each component is:
Preparation method: above-mentioned lignocaine, chitosan, Herba Rosmarini Officinalis extract through powdered is fully dissolved in 3.00g dehydrated alcohol, settled solution is transferred in aerosol aluminium pot, sealing-in aerosol pump, is pressed into 24.75g propellant tetrafluoroethane, obtains stable medicinal aerosol.
Embodiment 5
The consumption of each component is:
Preparation method: above-mentioned lignocaine, Aloe extract, chitosan, Herba Rosmarini Officinalis extract through powdered is fully dissolved in 3.00g dehydrated alcohol, settled solution is transferred in aerosol aluminium pot, sealing-in aerosol pump, be pressed into 22.25g propellant tetrafluoroethane, obtain stable medicinal aerosol.
Embodiment 6
The consumption of each component is:
Preparation method: above-mentioned lignocaine, Aloe extract, chitosan, Herba Rosmarini Officinalis extract through powdered is fully dissolved in 3.00g propylene glycol, settled solution is transferred in aerosol aluminium pot, sealing-in aerosol pump, be pressed into 22.25g propellant tetrafluoroethane, obtain stable medicinal aerosol.
Embodiment 7
The consumption of each component is:
Preparation method: above-mentioned lignocaine, Aloe extract, chitosan, Herba Rosmarini Officinalis extract antioxidant through powdered is fully dissolved in 3.00g dehydrated alcohol, settled solution is transferred in aerosol aluminium pot, sealing-in aerosol pump, be pressed into 22.25g propellant tetrafluoroethane, obtain stable medicinal aerosol.
Embodiment 8
Preparation method: above-mentioned lignocaine, Aloe extract, chitosan, Herba Rosmarini Officinalis extract through powdered is fully dissolved in 3.00g propylene glycol, settled solution is transferred in aerosol aluminium pot, sealing-in aerosol pump, is pressed into 22.75g propellant iso-butane, obtains stable medicinal aerosol.
Embodiment 9
The consumption of each component is:
Preparation method: above-mentioned lignocaine, Aloe extract, chitosan, Herba Rosmarini Officinalis extract through powdered is fully dissolved in 3.00g dehydrated alcohol, settled solution is transferred in aerosol aluminium pot, sealing-in aerosol pump, be pressed into 22.34g propellant tetrafluoroethane, obtain stable medicinal aerosol.
Embodiment 10
The consumption of each component is:
Preparation method: above-mentioned lignocaine, Aloe extract, chitosan, Herba Rosmarini Officinalis extract through powdered is fully dissolved in 3.00g dehydrated alcohol, settled solution is transferred in aerosol aluminium pot, sealing-in aerosol pump, be pressed into 17.25g propellant tetrafluoroethane, obtain stable medicinal aerosol.
Embodiment 11
The consumption of each component is:
Preparation method: above-mentioned lignocaine, Aloe extract, chitosan, Herba Rosmarini Officinalis extract through powdered is fully dissolved in 3.00g dehydrated alcohol, settled solution is transferred in aerosol aluminium pot, sealing-in aerosol pump, be pressed into 22.25g propellant heptafluoro-propane, obtain stable medicinal aerosol.
Embodiment 12
The consumption of each component is:
Preparation method: above-mentioned lignocaine, Aloe extract, chitosan, Herba Rosmarini Officinalis extract antioxidant through powdered is fully dissolved in 3.00g propylene glycol, settled solution is transferred in aerosol aluminium pot, sealing-in aerosol pump, be pressed into 22.25g propellant heptafluoro-propane, obtain stable medicinal aerosol.
Embodiment 13
The consumption of each component is:
Preparation method: above-mentioned lignocaine, Aloe extract, chitosan, Herba Rosmarini Officinalis extract through powdered is fully dissolved in 2.00g dehydrated alcohol, settled solution is transferred in aerosol aluminium pot, sealing-in aerosol pump, be pressed into 24.25g propellant heptafluoro-propane, obtain stable medicinal aerosol.
Embodiment 14
The consumption of each component is:
Preparation method: above-mentioned lignocaine, Aloe extract, chitosan, Herba Rosmarini Officinalis extract through powdered is fully dissolved in 3.00g dehydrated alcohol, settled solution is transferred in aerosol aluminium pot, sealing-in aerosol pump, be pressed into tetrafluoroethane that total amount is 25.25g and the mixing propellant of dichlorodifluoromethane, obtain stable medicinal aerosol.
Embodiment 15
The consumption of each component is:
Preparation method: above-mentioned lignocaine, Aloe extract, chitosan, Herba Rosmarini Officinalis extract through powdered is fully dissolved in 3.00g dehydrated alcohol, settled solution is transferred in aerosol aluminium pot, sealing-in aerosol pump, being pressed into total amount is the mixing propellant of tetrafluoroethane/dichlorodifluoromethane of 22.25g, obtains stable medicinal aerosol.
Embodiment 16
The consumption of each component is:
Preparation method: above-mentioned lignocaine, Aloe extract, chitosan, Herba Rosmarini Officinalis extract through powdered is fully dissolved in 3.00g dehydrated alcohol, settled solution is transferred in aerosol aluminium pot, sealing-in aerosol pump, be pressed into 24.25g propellant heptafluoro-propane, obtain stable medicinal aerosol.
Comparative example 1
The consumption of each component is:
Preparation method: above-mentioned lignocaine, Herba Rosmarini Officinalis extract through powdered is fully dissolved in 3g dehydrated alcohol, settled solution is transferred in aerosol aluminium pot, sealing-in aerosol pump, is pressed into 25.25g propellant tetrafluoroethane, obtains medicinal aerosol.
Comparative example 2
The consumption of each component is:
Preparation method: above-mentioned lignocaine, Herba Rosmarini Officinalis extract antioxidant through powdered is fully dissolved in 3g dehydrated alcohol, settled solution is transferred in aerosol aluminium pot, sealing-in aerosol pump, is pressed into 23.75g propellant dichlorodifluoromethane, obtains medicinal aerosol.
The aerosol film property contrast test of embodiment and comparative example
Apart from 10cm place, successively by aerosol spray on clean, dry glass plate, observe the film property of aerosol after spraying, result is as follows:
The contrast of table 1 film property
Prescription |
Film formation time (min) |
Film property |
Embodiment 1 |
5 |
Size ratio is compared with homogeneous, thickness homogeneous |
Embodiment 2 |
5 |
Size ratio is compared with homogeneous, thickness homogeneous |
Embodiment 3 |
5 |
Size ratio is compared with homogeneous, thickness homogeneous |
Embodiment 4 |
5 |
Size ratio is compared with homogeneous, thickness homogeneous |
Embodiment 5 |
4 |
Uniform particle diameter, thickness homogeneous |
Embodiment 6 |
4 |
Uniform particle diameter, thickness homogeneous |
Embodiment 7 |
4 |
Uniform particle diameter, thickness homogeneous |
Embodiment 8 |
3 |
Uniform particle diameter, thickness homogeneous |
Embodiment 9 |
4 |
Uniform particle diameter, thickness homogeneous |
Embodiment 10 |
3 |
Uniform particle diameter, thickness homogeneous |
Embodiment 11 |
5 |
Uniform particle diameter, thickness homogeneous |
Embodiment 12 |
4 |
Uniform particle diameter, thickness homogeneous |
Embodiment 13 |
4 |
Uniform particle diameter, thickness homogeneous |
Embodiment 14 |
4 |
Uniform particle diameter, thickness homogeneous |
Embodiment 15 |
4 |
Uniform particle diameter, thickness homogeneous |
Embodiment 16 |
4 |
Uniform particle diameter, thickness homogeneous |
Comparative example 1 |
6 |
Thicker, particle diameter heterogeneity |
Comparative example 2 |
6 |
Very thick, particle diameter heterogeneity |
From table 1, embodiment and comparative example film formation time and film-formation result compare discovery, and the Lidocaine Aerosol that is added with Aloe extract and/or chitosan does not add Aloe extract and/or chitosan has good film property.
When the mass ratio of chitosan and Aloe extract is when certain limit (1.5-3.0), the needed shortest time of aerosol film forming (only needing 3 minutes).
Clinical trial:
The sample of above-mentioned preparation, for clinical patient, is drawn to following experimental result by patient's reaction directly perceived and the observation of skin surface.Wherein, in following course of injection, each metering that uses ejection is 200umL.The aerosol that sprays embodiment 1-16 once after, the skin of mosquito bite reaches antipruritic good result about 15 minutes, there is no pruritus.Slight scald, the skin of scratch is after 24 hours, and skin wound is red and swollen to be eliminated, and color is normal, then after 24 hours, skin heals normally substantially.Be used for alleviating the symptoms such as myalgia, spray above-mentioned sample once after, be onset in 15 minutes.And by observing, the aerosol in embodiment does not have obvious stimulation to skin.When each aerosol that sprays the same comparative example who measures 1,2 preparations, it also has certain antipruritic effect to mosquito bite, but needs multi-injection just can obtain certain remission effect to skin and after 3-6 hour.And during for slight scald, scratch, its healing effect is equally very slow, need to pass through multi-injection.