CN104689035A - Aerosol precursor containing pharmacodynamic ingredients of Chuanbei Pipa syrup and method for dispersing aerosol precursor into nano-scale frog drops - Google Patents

Aerosol precursor containing pharmacodynamic ingredients of Chuanbei Pipa syrup and method for dispersing aerosol precursor into nano-scale frog drops Download PDF

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Publication number
CN104689035A
CN104689035A CN201510100211.7A CN201510100211A CN104689035A CN 104689035 A CN104689035 A CN 104689035A CN 201510100211 A CN201510100211 A CN 201510100211A CN 104689035 A CN104689035 A CN 104689035A
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China
Prior art keywords
bulbus fritillariae
fritillariae cirrhosae
aerosol precursor
saurauiae tristylae
active ingredient
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CN201510100211.7A
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Chinese (zh)
Inventor
韩敬美
杨柳
赵伟
田永峰
杨继
杨钰婷
段沅杏
秦云华
陈永宽
缪明明
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China Tobacco Yunnan Industrial Co Ltd
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China Tobacco Yunnan Industrial Co Ltd
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Priority to CN201510100211.7A priority Critical patent/CN104689035A/en
Publication of CN104689035A publication Critical patent/CN104689035A/en
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Abstract

The invention relates to an aerosol precursor containing pharmacodynamic ingredients of Chuanbei Pipa syrup. The aerosol precursor contains glycerol, propanediol, 1,3-butanediol, an aromatic substance and a Chuanbei Pipa syrup extract in a mass ratio of (40-45):(20-25):(0-10):(0-10):(1-10). The invention also relates to a method for dispersing the pharmacodynamic ingredients of Chuanbei Pipa syrup into nano-scale frog drops, and also relates to an aerosol containing the nano-scale frog drops. The aerosol precursor provided by the invention contains the pharmacodynamic ingredients of the Chuanbei Pipa syrup, and the nano-scale frog drops can be obtained by heating the aerosol precursor in an electronic cigarette smoking set comprising an electric heating device, so that the aerosol precursor is more beneficial for a human body to absorb the pharmacodynamic ingredients.

Description

A kind ofly comprise the aerosol precursor of Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae active ingredient and be dispersed into the method for nanometer-sized mist droplets
Technical field
The present invention relates to a kind of aerosol precursor, be specifically related to a kind ofly comprise the aerosol precursor of Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae active ingredient and be dispersed into the method for nanometer-sized mist droplets.
Background technology
The main component of Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae is Bulbus Fritillariae Cirrhosae fluidextract, Radix Platycodonis, Folium Eriobotryae, Mentholum.It is henna thick liquid; Gas is fragrant, sweet, the micro-hardship of taste, cool, has reducing heat and dispersing lung-QI, effect of preventing phlegm from forming and stopping coughing.Usually, the administering mode of Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae is oral administration, and drug action is slow on the one hand for such administering mode; Medicine can be brought the zest of the intestines and stomach on the one hand; On the other hand, the first pass effect of liver can make utilization ratio of drug decline.
Aerosol be commonly referred to as when be heated or pressurized can produce the preparation of droplet.In medicinal pharmacology field, aerosol means the ejection in spray in use of pastille liquid, emulsion or suspension, sucks or be directly sprayed onto the preparation of tract mucosa, skin and space disinfection for pulmonary.Aerosol drug delivery has the following advantages: (1) medicine can directly arrive site of action or absorption site, has fairly obvious quick-acting roles and positioning effects, in respiratory tract administration, especially has the irreplaceable advantage of other dosage forms; (2) non-oral administration can reduce medicine to gastrointestinal zest, and can avoid the first pass effect of liver.
Usual inhalation aerosol should check droplet (grain) size distribution, and usual inhalation aerosol requires that its mean diameter should control below 10 μm, preferably below 5 μm.The method of the atomization of liquid has pressure atomization, rotary disk atomisation, gas atomization and sound wave atomization etc.It is micron-sized droplet that these atomizing types only can obtain mean diameter usually.
The representative patents of compound Chinese medicinal preparation being carried out to pressurizing atomizing is CN102949573A, the propellant of 80-100bar such as isceon, dichlorodifluoromethane or dichlorotetra-fluoroethane wherein will be used just to obtain micron order droplet to be atomized medicinal liquid, above-mentioned expulsion pressure is too high, holding tank air-tightness to propellant requires harsh, production cost is high, and propellant itself also cost is high.In addition, the mode of this pressurizing atomizing is along with the increase of drug use amount, and in tank, pressure constantly reduces, and medicinal atomized effect is also deteriorated gradually; Further, such tank for consumers only can single use, adds use cost.
Therefore, this area is atomized into the method for micron order droplet in the urgent need to a kind of Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae that can make in atmospheric conditions, and preferably can reduce the diameter of droplet further, so that the degree of scatter of raising medicinal liquid is to improve absorption of human body efficiency further.
Summary of the invention
The object of the present invention is to provide and a kind ofly comprise the aerosol precursor of Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae active ingredient and be dispersed into the method for nanometer-sized mist droplets, user sucks containing the nanometer-sized mist droplets comprising Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae active ingredient, more effectively can absorb medicinal ingredient wherein.
First aspect present invention relates to a kind of aerosol precursor comprising Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae active ingredient, it comprises glycerol, propylene glycol, 1,3-butanediol, fragrance matter and Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae extractum, their mass ratio is glycerol: propylene glycol: 1,3 butylene glycol: fragrance matter: Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae extractum=(40-45): (20-25): (0-10): (0-10): (1-10).Wherein, the precursor of aerosol described in the present invention refer to when be heated or pressurized can produce droplet, during use can in the pastille liquid of spray, the general designation of emulsion or suspension etc.The Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae related in the present invention refers to the Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae of required standard in " Chinese Pharmacopoeia " version in 2010, namely prescription is Bulbus Fritillariae Cirrhosae fluidextract 45ml, Radix Platycodonis 45g, Folium Eriobotryae 300g, Mentholum 0.34g, method for making is above four tastes, Bulbus Fritillariae Cirrhosae 45g gets in Bulbus Fritillariae Cirrhosae fluidextract system, be ground into coarse powder, use 70% ethanol as solvent, flood after 5 days, slowly percolation, collect just percolate 38ml, another device is preserved, continue percolation, soluble component of waiting is filtered out completely, continuous percolate is concentrated in right amount, mix with first percolate, continue to be concentrated into 45ml, filter.Radix Platycodonis and Folium Eriobotryae decoct with water secondary, 2.5 hours first times, second time 2 hours, collecting decoction, filter, filtrate is concentrated in right amount, add sucrose 400g and Preservative qs, boil and make dissolving, filter, filtrate mixes with Bulbus Fritillariae Cirrhosae fluidextract, let cool, add Mentholum and the alcoholic solution containing appropriate almond essence, add water to 1000ml, stir evenly, to obtain final product.。Including within the scope of this invention with the Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae sold of preparing of relevant criterion in good grounds " Chinese Pharmacopoeia ".
In application process, in Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae active ingredient, part can be dissolved in glycerol equal solvent; Part can with glycerol etc. for carrier, and be adsorbed on carrier surface by hydrogen bond action etc., the movement with carrier is transported to site of action.
Wherein said fragrance matter comprises conventional edible spice, such as 2,3-diacetyl, butyl phenylacetate, β-caryophyllene, dorinone etc.Preferably, described fragrance matter comprises nicotine, i.e. nicotine.
In preferred embodiments, described Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae extractum is obtained by the method comprised the following steps:
(1) remove impurity: be dissolved in by Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae in food grade ethanol, filters, removes insoluble impurity, obtain the alcoholic solution of Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae;
(2) decolour: by the alcoholic solution of Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae that obtains in step (1) by the first macroporous resin chromatography, and use ethanol-water solution eluting, remove pigment composition wherein;
(3) except sugar: by the ethanol water that obtains in step (2) by the second macroporous resin chromatography, and use ethanol-water solution eluting, remove carbohydrate content wherein, and utilize molecular distillation to remove desolventizing, obtain the first extractum;
(4) active ingredient extracts: with the first extractum obtained in acetic acid aqueous solution dissolving step (3), recycling organic solvent abstraction impurity removal from aqueous solution, retain water layer after layering, then utilize molecular distillation to dewater, obtain described Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae extractum; Wherein, described acetic acid aqueous solution is used for the main active substances alkaloids in extraction first extractum.
In preferred embodiments, in described step (2), the ethanol-water solution concentration range of eluting macroporous resin chromatography is 40-70 volume %; Independently, in described step (3), the ethanol-water solution concentration range of eluting macroporous resin is 70-90 volume %; Independently, the organic solvent in described step (4) is selected from ethyl acetate, dichloromethane, chloroform, cyclohexane extraction or normal hexane.
In preferred embodiments, described step (3) Middle molecule distillation apparatus condition is: feed rate 0.8-1.0kgh -1, feeding temperature 30-50 DEG C, vapo(u)rizing temperature 40-50 DEG C, the pressure 200-300Pa of distillation, scraper plate rotating speed 100-150rmin -1.
In preferred embodiments, described step (4) Middle molecule distillation apparatus condition is: feed rate 0.5-1.0kgh -1, feeding temperature 30-40 DEG C, vapo(u)rizing temperature 50-70 DEG C, the pressure 250-300Pa of distillation, scraper plate rotating speed 100-150rmin-1.
Second aspect present invention relates to a kind of method active ingredient in Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae being dispersed into nanometer-sized mist droplets, it is the aerosol precursor comprising Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae active ingredient heated in the electronic cigarette smoking set comprising electric heating device as described in the first aspect of the invention, make it be heated and be atomized into nanometer-sized mist droplets, in this nanometer-sized mist droplets, be loaded with the active ingredient in Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae.
In preferred embodiments, described electronic cigarette smoking set also has supersonic generator part, strengthens atomizing effect to apply supersonic oscillations to described aerosol precursor.
Third aspect present invention relates to a kind of aerosol comprising nanometer-sized mist droplets, and described nanometer-sized mist droplets comprises Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae active ingredient, and the particle size range of wherein said nanometer-sized mist droplets is 100-300nm.
Fourth aspect present invention relates to the aerosol that another kind comprises nanometer-sized mist droplets, described nanometer-sized mist droplets comprises Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae active ingredient, and it is by carrying out heating atomization by the aerosol precursor comprising Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae active ingredient described in first aspect present invention and obtaining.
Fifth aspect present invention relates to a kind of electronic cigarette tobacco tar, and it comprises the aerosol precursor described in first aspect present invention.Electronic cigarette tobacco tar of the present invention, compared to the electronic cigarette tobacco tar of routine, its sweet soapy feeling reduces greatly.
Beneficial effect of the present invention:
1, the aerosol precursor comprising Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae active ingredient of the present invention passes through to heat in the electronic cigarette smoking set comprising electric heating device, without the need to using the propellant of pressurization, just make it be heated to be atomized into the nanometer-sized mist droplets of the active ingredient be loaded with in CHUANBEI PIPA GAO, its particle size range is 100-300nm, and every mouthful of suction aerosol Particle density and size have concordance; Compared to common aerosol, after electronic cigarette atomizing, active ingredient can be atomized out along with flue gas, and particle diameter is nanoscale, not only specific surface area is larger, more easily absorbed by alveolar cell, and nanometer-sized mist droplets more easily enters into human respiratory tract, particularly Conventional aerosol is difficult to the lower respiratory tract depths of arrival, and is more conducive to absorption of human body active ingredient;
2, present invention utilizes the droplet carrier that electronic cigarette atomizing forms nanometer diameter, active ingredient is made to adhere to or be dissolved on droplet, then be drawn in human body through oral cavity, directly act on respiratory system, overcome Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae active ingredient oral after loss in digestion and blood circulation, improve the effective rate of utilization of active ingredient in Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae;
3, the present invention can make active ingredient in Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae be directly acted on by nano-carrier or be deposited on the oral cavity of human body, throat, upper respiratory tract and lower respiratory tract, shortens the action time of active ingredient in human body;
4, in the present invention, Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae is carried out desaccharide process, avoiding commercially available Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae diabetics cannot the defect of medication, and applicable colony is more extensive;
5, Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae extractum is comprised in electronic cigarette tobacco tar of the present invention by adding, the sweet soapy feeling of electronic cigarette tobacco tar itself can also be reduced, a kind of electronic cigarette tobacco tar with medical value and good suction impression is provided, smoking is become from being harmful to health and is good for one's health.
Detailed description of the invention
The invention is further illustrated by the following examples, should be appreciated that embodiment only in order to explain the present invention, the restriction not to technical solution of the present invention.
Embodiment 1
A kind of aerosol precursor comprising Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae active ingredient, it comprises glycerol, propylene glycol, 1,3-butanediol, fragrance matter and Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae extractum, their mass ratio is glycerol: propylene glycol: Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae extractum=40:20:1.
Wherein said Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae extractum is obtained by the method comprised the following steps:
(1) remove impurity: be dissolved in by Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae in food grade ethanol, filters, removes insoluble impurity, obtain the alcoholic solution of Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae;
(2) decolour: by the alcoholic solution of Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae that obtains in step (1) by the first macroporous resin chromatography, and be the ethanol-water solution eluting of 40 volume % with concentration, remove pigment composition wherein; The model of wherein said first macroporous resin chromatography is preferably MCIGEL CHP20P (75-150 μm).
(3) except sugar: by the ethanol water that obtains in step (2) by the second macroporous resin chromatography, and be the ethanol-water solution eluting of 70 volume % by concentration, removing carbohydrate content wherein, and utilize molecular distillation to remove desolventizing, obtain the first extractum; Wherein molecular distillation instrument condition is: feed rate 0.8kgh -1, feeding temperature 30 DEG C, vapo(u)rizing temperature 40 DEG C, the pressure 200Pa of distillation, scraper plate rotating speed 100rmin -1;
(4) active ingredient extracts: with the first extractum obtained in acetic acid aqueous solution dissolving step (3), recycling ethyl acetate abstraction impurity removal from aqueous solution, retain water layer after layering, then utilize molecular distillation to dewater, obtain described Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae extractum; Wherein molecular distillation instrument condition is: feed rate 0.5kgh -1, feeding temperature 30 DEG C, vapo(u)rizing temperature 50 DEG C, the pressure 250Pa of distillation, scraper plate rotating speed 100rmin -1.
The above-mentioned aerosol precursor comprising Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae active ingredient is heated in the electronic cigarette smoking set comprising electric heating device and supersonic generator part, make it be heated and be atomized into nanometer-sized mist droplets, in this nanometer-sized mist droplets, be loaded with the active ingredient in Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae.Be 201410380290.7 by number of patent application, the method of aerosol particle diameter is measured disclosed in title " a kind of method evaluating electronic cigarette amount of smoke ", the particle size range recording the droplet of the active ingredient be wherein loaded with in Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae is 100-300nm, compared with the mist droplet particle size of the 4-1000nm after being atomized with conventional electrical cigarette ree-oil distributes, mist droplet particle size distribution after aerosol precursor of the present invention atomization is more concentrated, and this may owing to having the interaction of certain the unknown to cause between the Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae that adds and ree-oil.
As can be seen from embodiment 1, the mist droplet particle size scope of the active ingredient be loaded with in Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae of the present invention is nanoscale, is more conducive to entering human respiratory tract depths and being absorbed by the body, has good proper value.

Claims (10)

1. one kind comprises the aerosol precursor of Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae active ingredient, it is characterized in that, it comprises glycerol, propylene glycol, 1,3-butanediol, fragrance matter and Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae extractum, their mass ratio is glycerol: propylene glycol: 1,3 butylene glycol: fragrance matter: Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae extractum=(40-45): (20-25): (0-10): (0-10): (1-10).
2. aerosol precursor according to claim 1, is characterized in that, described Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae extractum is obtained by the method comprised the following steps:
(1) remove impurity: be dissolved in by Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae in food grade ethanol, filters, removes insoluble impurity, obtain the alcoholic solution of Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae;
(2) decolour: by the alcoholic solution of Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae that obtains in step (1) by the first macroporous resin chromatography, and use ethanol-water solution eluting, remove pigment composition wherein;
(3) except sugar: by the ethanol water that obtains in step (2) by the second macroporous resin chromatography, and use ethanol-water solution eluting, remove carbohydrate content wherein, and utilize molecular distillation to remove desolventizing, obtain the first extractum;
(4) active ingredient extracts: with the first extractum obtained in acetic acid aqueous solution dissolving step (3), recycling organic solvent abstraction impurity removal from aqueous solution, retain water layer after layering, then utilize molecular distillation to dewater, obtain described Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae extractum.
3. aerosol precursor according to claim 2, is characterized in that, in described step (2), the ethanol-water solution concentration range of eluting macroporous resin chromatography is 40-70 volume %; Independently, in described step (3), the ethanol-water solution concentration range of eluting macroporous resin is 70-90 volume %; Independently, the organic solvent in described step (4) is selected from ethyl acetate, dichloromethane, chloroform, cyclohexane extraction or normal hexane.
4. aerosol precursor according to claim 2, is characterized in that, described step (3) Middle molecule distillation apparatus condition is: feed rate 0.8-1.0kgh -1, feeding temperature 30-50 DEG C, vapo(u)rizing temperature 40-50 DEG C, the pressure 200-300Pa of distillation, scraper plate rotating speed 100-150rmin -1.
5. aerosol precursor according to claim 2, is characterized in that, described step (4) Middle molecule distillation apparatus condition is: feed rate 0.5-1.0kgh -1, feeding temperature 30-40 DEG C, vapo(u)rizing temperature 50-70 DEG C, the pressure 250-300Pa of distillation, scraper plate rotating speed 100-150rmin -1.
6. the active ingredient in Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae is dispersed into the method for nanometer-sized mist droplets by one kind, it is characterized in that, the aerosol precursor that comprise Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae active ingredient of heating according to any one of claim 1-5 in the electronic cigarette smoking set comprising electric heating device, make it be heated and be atomized into nanometer-sized mist droplets, in this nanometer-sized mist droplets, be loaded with the active ingredient in Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae.
7. method according to claim 6, is characterized in that, described electronic cigarette smoking set also has supersonic generator part.
8. comprise an aerosol for nanometer-sized mist droplets, described nanometer-sized mist droplets comprises Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae active ingredient, it is characterized in that, the particle size range of wherein said nanometer-sized mist droplets is 100-300nm.
9. one kind comprises the aerosol of nanometer-sized mist droplets, described nanometer-sized mist droplets comprises Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae active ingredient, it is characterized in that, it is by carrying out heating atomization by the aerosol precursor comprising Syrupus Bulbus Fritillariae Cirrhosae et Radix Saurauiae Tristylae active ingredient according to any one of claim 1-5 and obtaining.
10. an electronic cigarette tobacco tar, is characterized in that, it comprises the aerosol precursor according to any one of claim 1-5.
CN201510100211.7A 2015-03-06 2015-03-06 Aerosol precursor containing pharmacodynamic ingredients of Chuanbei Pipa syrup and method for dispersing aerosol precursor into nano-scale frog drops Pending CN104689035A (en)

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CN105146729A (en) * 2015-06-30 2015-12-16 佛山市万绿素电子科技有限公司 Electronic cigarette tar with cough stopping and throat wetting functions
CN110090262A (en) * 2018-01-30 2019-08-06 北京盈科瑞创新药物研究有限公司 A kind of Compound Loquat cough-relieving sucking pharmaceutical solutions and preparation method thereof

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Publication number Priority date Publication date Assignee Title
CN105146729A (en) * 2015-06-30 2015-12-16 佛山市万绿素电子科技有限公司 Electronic cigarette tar with cough stopping and throat wetting functions
CN110090262A (en) * 2018-01-30 2019-08-06 北京盈科瑞创新药物研究有限公司 A kind of Compound Loquat cough-relieving sucking pharmaceutical solutions and preparation method thereof

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Application publication date: 20150610

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