CN102988979B - Artemisia pollen allergen vaccine lozenge and preparation method thereof - Google Patents
Artemisia pollen allergen vaccine lozenge and preparation method thereof Download PDFInfo
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Abstract
The invention provides Artemisia pollen allergen vaccine lozenge and a preparation method thereof, wherein the lozenge is prepared by mixing idiotoxins of five kinds of sensitized Artemisia pollens and pharmaceutically acceptable carriers; and the five kinds of sensitized Artemisia plants are Artemisia sieversiana Willd, Artemisia annua L., Artemisia argyi Levl.et Vant, A.ordosica krasch and A.sphaerocep hala krasch. The Artemisia pollen allergen vaccine disclosed by the invention includes idiotoxins of five kinds of main sensitized Artemisia pollens in China; compared with the single Artemisia pollen allergen vaccine, the Artemisia pollen allergen vaccine disclosed by the invention is more effective; furthermore, compared with the sublingual drop, the sublingual lozenge is more steady; and the administration dosage is more accurate.
Description
Technical field
The present invention relates to allergen vaccine preparation field, specifically, relate to a kind of Artemisia pollen allergen vaccine buccal tablet and preparation method thereof.
Background technology
The mankind start from " Hay Fever " for the understanding of allergen disease, and scientist noon in 1911 and freeman utilize pollen extracting liquid to treat Hay Fever first, and allergen disease treatment raises the curtain thus.The development of China's allergen disease treatment is by the department of otorhinolaryngology director Zhang Qingsong of Concord Hospital professor, from the U.S., to be introduced for 1956 the earliest, and obtained breakthrough, found that Chinese most important autumn type pollen is artemisia (Artemisia) plant pollen, for developing national allergen, realize the localized road of allergen foundation is provided.The eighties was passed pollen investigation and was shown by take the lead Chinese gas that tens of the hospitals in the whole nation complete of Ye Shitai, Qiao Bingshan last century, and what many areas Pollens content summer and autumn was maximum is artimesia.Zhao Jing etc. find in 13～14 years old childrens respiratory tract anaphylactic disease Epidemiological study of Beijing area: artimesia sensitive subjects is 5.7%.After this, in China each department, Artemisia pollen-induced is carried out to a large amount of investigation of clinical epidemiology, result is as follows:
The main allergen that shows Huhehaote City's induced hypersensitivity rhinitis in Duan Zhijian < < Huhehaote City anaphylactogen distribution situation and clinical analysis > > is artimesia.
Area, Zhang Kesheng < < Huhehaote gas passes with the discussion > > result of pollen and shows that the main pollen in area, Huhehaote is artimesia.
The high < < of the Meng and Bao Li urban district of Hohhot allergic rhinitis in autumn crowd analysis about allergen detection > >: area, Huhehaote main allergen in autumn is sagebruss, Artemisia apiacea pollen, accounts for certain proportion to dirt demodicid mite, DMS person.
The research > > of Liu Guanghui < < survey of main allergic pollen in pollinosis in district of Wuhan; Liu Guanghui, wish that floss flies that < < Wuhan Area artimesia distributes and Allergic Rhinitis airway reactivity affected to > >: artimesia is one of Wuhan Urban main pollen in autumn.
Main pollen investigation > > in the air of Yang Jiong < < Wuchang Area: artimesia is this area main pollen summer and autumn.
Area, Jingmen, the male < < Hubei Province of Dong Shang gas passes pollen and allergic asthma dependency > >: Jingmen pollen in main autumn is artimesia.
Zhang Hongyu < < Beijing gas passes artimesia concentration investigation > >: Beijing area is within artimesia clinical season, and daily mean of concentration is at 100g/m
3.
The application > > in allergic rhinitis etiological diagnosis is tested in Zhao Yan < < Ah Roger pricking method: artimesia is the common anaphylactogens of Jingmen area allergic rhinitis.
The routine sensitinogen of the flat < < of Cao Sui allergic disease 201 is analyzed > >: the main pollen in Yulin Prefecture, Shaanxi Province is artimesia.
Area, the Respiratory Medicine < < of attached institute of Xian Medical Univ two Xi'an gas passes the dynamic preliminary survey > of pollen >: Xi'an main pollen in area autumn is artimesia.
The blue < < of the Wei Xiu of Second Hospital of Shanxi Medical University Shanxi Province 1298 example time allergen measurement results are analyzed > >: artimesia is Shanxi area childhood asthma allergen principal element.
Datong the 3rd the People's Hospital allergy Ke Li state qin < < Datong area 240 routine pollinosis antigen skin tests and clinical analysis > >: in pollen source, Datong area, artimesia tops the list.
The routine allergic rhinitis skin test interpretation of result > > in Zhang Xingyong < < Lanzhou, allergy chamber, hospital general, Lanzhou, the military region 224; The routine pollinosis in < < Lanzhou 87 is analyzed > >; The reactive rhinitis investigation report of portion of < < air force mass-sending paraphilia > >; The Chen Lin < < of intrathoracic section of district hospital of army Lanzhou, Lanzhou gas passes pollen preliminary survey > >: the main pollen in Lanzhou is artimesia.
The routine pollinosis patient allergen in < < Luoyang city 360 is analyzed > >: University Of Science and Technology Of He'nan the 3rd Affiliated Hospital's allergy chamber, it is artimesia that the main pollen of pollinosis and symptoms of asthma is induced autumn in Foundation of Luoyang.
The precious < < Maanshan district 100 routine allergic rhinitis patients' of 19 He Hong of smelting hospital antigen and desensitization observation of curative effect > >: the Maanshan district main inhalation (inhalatio) of allergic rhinitis sensitinogen is indoor dust, dust mite, artimesia capsule and polyvalent fungus.
Sun Juan < < gas passes the regional investigation of pollen present situation > >: all there is Artemisia pollen-induced China eight major regions.
In Li Quanwen < < Shandong Province three city's air, gas passes and pollen investigation > >: the main pollen in Jinan City, Shandong Province, Weifang and Yantai is artimesia.
Above artimesia epidemiological investigation shows, Artemisia pollen-induced each area of China that extensively distributes, is allergic rhinitis and asthma main pathogenic at northern area artimesia.
Artemisia (Artemisia) plant is 1-2 or perennial herb, rare shrub, and the normal strong fragrance of tool, has root shape neck and nutrition branch more.How upright stem is, and the shape of partly growing thickly has obviously vertical rib; Plant is often by floss hair; Leaf alternate, most featheriness divisions; Head inflorescence is little, and base portion often has squamella; Spend the opposite sex, edge is spent female, central authorities' flower both sexes.The pollen characteristic of artemisia has high consistency, is mainly reflected in pollen spherical in shape or subsphaeroidal, and polar view is three and splits circular tool three hole ditches, and equatorial view is circular or oval.Most chromosome numbers of planting are 2n=18, and the chromosome number of minority kind is 2n=36.It originates in temperate zone, cool temperature zone and the subtropical zone in Asia, Europe and North America.In North America and Europe, main irritated artimesia is Artemisia apiacea pollen, China's artimesia comprises 186 kinds and 44 mutation, spreads all over the country, and northwest, North China, northeast and southwestern provinces and regions are maximum, East China, Central China, south China are less slightly, are born in barren hill, wilderness and roadside more.
China's artimesia distributes the widest, has confirmed clinically to cause the pollen of people's allergy to comprise three kinds: Artemisia apiacea pollen (Artemisia argyi Levl.et Vant), Artemisia sieversiana Willd. pollen (Artemisiasieversiana Wild), Herba Artemisiae annuae pollen (Artemisiaannua L).
Artemisia injection prepared by the allergic effect Drug Manufacturing Room of Concord Hospital, Herba Artemisiae annuae pollen allergen injection at home hundreds of of various places hospital have been used decades, effectively suppress the transformation of China's Artemisia pollen-induced rhinitis to allergic asthma, effectively alleviated the symptom of China Artemisia pollen-induced sexually transmitted disease (STD) people asthma.
Beijing New Hualian consonance Pharmaceutical in 2011 is propagated season (July-October) and has been carried out an Epidemiological study at artimesia, to the patient of doubtful Artemisia pollen-induced pricking method simultaneously Artemisia apiacea pollen allergen pricking method liquid, Artemisia pricking method liquid, Herba Artemisiae annuae pollen allergen pricking method liquid.This time investigation of clinical epidemiology result shows: in China, three kinds of artimesias exist cross allergy, although different patient is to three kinds of Artemisia pollen allergen extent of reaction property of there are differences.In China, also have different types of artimesia, existing still report proves whether other artimesia causes people's allergy.Press the popularity of artimesia distribution, China's artimesia is topmost is Herba Artemisiae annuae pollen, Artemisia sieversiana Willd. pollen, Artemisia apiacea pollen (seeing that < < China gas passes pollen and plant color collection of illustrative plates > >).Other artimesia is compared this three kinds of artimesias, distribution and energy for growth are relatively little, moreover there is cross immunity originality in Artemisia pollen-induced, Herba Artemisiae annuae pollen, Artemisia sieversiana Willd. pollen, Artemisia apiacea pollen are widely distributed, pollen raw material is easier to collect, and therefore these three kinds of artimesias are suitable material choice of preparation Artemisia pollen allergen vaccine.The Artemisia injection that the allergen Drug Manufacturing Room of BJ Union Hospital produce and Herba Artemisiae annuae pollen allergen injection have proved safe and effective, and the Artemisia apiacea pollen allergen injection in Europe and North America has proved safe and effective.
In recent years, along with the greening in China desert advances, in the Inner Mongol and Shaanxi one, be with, Herba artemisiae ordosicae and Folium et Caulis Caryopteridis growth are spread unchecked.In conjunction with the epidemiology of China's Artemisia pollen-induced, it is more effective than single Artemisia pollen allergen vaccine that Herba Artemisiae annuae pollen, Artemisia sieversiana Willd. pollen, Artemisia apiacea pollen, Herba artemisiae ordosicae pollen, Folium et Caulis Caryopteridis pollen are prepared Artemisia pollen allergen combined vaccine, the five kinds of more suitable China of Artemisia pollen allergen combined vaccine Artemisia pollen-induced patients' demand, compare the single vaccine of single Artemisia pollen allergen, when can guarantee safety, improved the effectiveness for the treatment of.
The method of allergen specific immunity treatment is mainly divided into subcutaneous injection administration immunization therapy and sublingual administration immunization therapy at present.The subcutaneous injection administration immunization therapy history of existing 100 years, its safety and effectiveness have been obtained proof.At the beginning of the nineties in last century, allergen Sublingual drop vaccine is born, and 1998, WHO announced allergen Sublingual drop vaccine safety and effective.The beginning of this century, Sublingual drop allergen vaccine is widely used in Europe, South America, Australia, Southeast Asia and Middle East.Sublingual drop allergen vaccine is compared subcutaneous injection administration allergen vaccine, safer, patient's medication of can going home voluntarily, and patient compliance is good, is easy to accept this therapeutic modality.In allergic rhinitis and asthma patient, child patient accounts for significant proportion, for children population patient, and Sublingual immunity drop allergen vaccine, patient compliance is better, acceptant this therapeutic modality.
But a shortcoming of Sublingual drop vaccine is, the dosage at every turn splashing into is difficult to control, and dosage inaccuracy, differs greatly, and prepares allergen vaccine buccal tablet more stable with respect to Sublingual drop, can realize homogenization administration.
Summary of the invention
The object of this invention is to provide a kind of Artemisia pollen allergen vaccine buccal tablet and preparation method thereof.
In order to realize the object of the invention, the invention provides a kind of Artemisia pollen allergen vaccine, the allergen that described vaccine comprises five kinds of sensitization artimesias, five kinds of sensitization sagebrusses are: Artemisia sieversiana Willd. (Artemisia sieversiana Willd), Herba Artemisiae annuae (Artemisia annua L.), Radix Artemisia ordosicae (Artemisia argyi Levl.et Vant), Herba artemisiae ordosicae (A.ordosica krasch) and Folium et Caulis Caryopteridis (A.sphaerocep hala krasch).
Aforesaid Artemisia pollen allergen vaccine, the allergenic activity ratio of five kinds of sensitization artimesias is preferably 1:1:1:1:1.
The preparation method of above-mentioned Artemisia pollen allergen vaccine, comprises the following steps:
1) by machinery (vacuum cleaner), gather or water culture is collected five kinds of artimesias, cross respectively 200～300 mesh sieves and remove the impurity such as dust in pollen, and pollen is carried out to purity detecting, and morphology and molecular biology identification.
2) pollen after remove impurity is used the defat of acetone soaking and stirring continuously, by the solids natural drying after defat.
3) pollen after extracting degreasing is respectively with 1:10～50(g:mL) rate of charge add in sodium hydrogen phosphate-phosphate sodium dihydrogen buffer solution of 50～500mM, 4 ℃ stir 4～24h.
4) by gained solution in step 3) successively through 8 μ m, 0.8 μ m, 0.45 μ m and 0.22 μ m membrane filtration.
5) the ultrafilter membrane weighing apparatus filter with molecular cut off 5kD by gained filtrate in step 4), until that filter liquor supernatant is the electrical conductivity of colourless or filter liquor is consistent with ultrafiltration buffer used, obtains each allergen vaccine stock solution.
6) with RSAT competition immunodepression, measure the activity of each vaccinogen liquid, be then mixed in proportion each vaccinogen liquid, obtain Artemisia pollen allergen vaccine.
The present invention also provides a kind of Artemisia pollen allergen vaccine buccal tablet, above-mentioned Artemisia pollen allergen vaccine and pharmaceutically acceptable carrier, consists of.
Aforesaid Artemisia pollen allergen vaccine buccal tablet, the percentage by weight of each component is:
Wherein, Artemisia pollen allergen vaccine: mannitol: crosslinked Carboxymethyl cellulose sodium: anhydrous silica gel: microcrystalline Cellulose: magnesium stearate: the weight ratio of Lactose hydrate is preferably 1:5:1:0.02:0.1:0.05:0.01.
The present invention also provides the preparation method of above-mentioned Artemisia pollen allergen vaccine buccal tablet, comprises the following steps:
1) by machinery (vacuum cleaner), gather or water culture is collected five kinds of artimesias, cross respectively 200～300 mesh sieves and remove the impurity such as dust in pollen, and pollen is carried out to purity detecting, and morphology and molecular biology identification.
2) pollen after remove impurity is used the defat of acetone soaking and stirring continuously, by the solids natural drying after defat.
3) pollen after extracting degreasing is respectively with 1:10～50(g:mL) rate of charge add in sodium hydrogen phosphate-phosphate sodium dihydrogen buffer solution of 50～500mM, 4 ℃ stir 4～24h.
4) by gained solution in step 3) successively through 8 μ m, 0.8 μ m, 0.45 μ m and 0.22 μ m membrane filtration.
5) the ultrafilter membrane weighing apparatus filter with molecular cut off 5kD by gained filtrate in step 4), until that filter liquor supernatant is the electrical conductivity of colourless or filter liquor is consistent with ultrafiltration buffer used, obtains each allergen vaccine stock solution.
6) with RSAT competition immunodepression, measure the activity of each vaccinogen liquid, be then mixed in proportion each vaccinogen liquid, obtain Artemisia pollen allergen vaccine.
7) to adding lyophilizing after mannitol in Artemisia pollen allergen vaccine.
8) powder after Artemisia pollen allergen vaccine freeze-drying and crosslinked Carboxymethyl cellulose sodium, anhydrous silica gel, microcrystalline Cellulose, magnesium stearate and Lactose hydrate are mixed in proportion to rear tabletting, vacuum packaging and get final product.
Artemisia pollen allergen vaccine sublingual lozenge provided by the invention comprises three concentration specifications: 50000AU/ sheet, 5000AU/ sheet, 500AU/ sheet.In use comprise two stages of dosage escalation and maintenance dose.
The present invention further provides the application for the anaphylactic disease of specific active immunotherapy Artemisia pollen-induced mediation of described Artemisia pollen allergen vaccine and Artemisia pollen allergen vaccine sublingual lozenge.Described anaphylactic disease comprises: allergic dermatitis, chronic urticaria, allergic rhinitis and allergic asthma etc.
In the present invention, described Artemisia is from Artemisia sieversiana Willd. pollen, to separate the Artemisia obtaining, described Herba Artemisiae annuae pollen allergen is from Herba Artemisiae annuae pollen, to separate the Herba Artemisiae annuae pollen allergen obtaining, described Artemisia apiacea pollen allergen is from Artemisia apiacea pollen, to separate the Artemisia apiacea pollen allergen obtaining, described Herba artemisiae ordosicae pollen allergen is from Herba artemisiae ordosicae pollen, to separate the Artemisia apiacea pollen allergen obtaining, and described Folium et Caulis Caryopteridis Artemisia pollen allergen is from Folium et Caulis Caryopteridis pollen, to separate the Folium et Caulis Caryopteridis pollen allergen obtaining.
Five kinds of selected Artemisia pollen allergen of Artemisia pollen allergen vaccine sublingual lozenge prepared by the present invention: Artemisia, Herba Artemisiae annuae pollen allergen, Artemisia apiacea pollen allergen, Herba artemisiae ordosicae pollen allergen and Folium et Caulis Caryopteridis pollen allergen are five kinds of Artemisia pollen allergen of the main sensitization of China, and its effectiveness is higher than single Artemisia pollen allergen.The vaccine of five kinds of Artemisia pollen allergen associatings has been included the main allergen of China's sensitization artimesia.The relative allergen vaccine of allergen vaccine sublingual lozenge Sublingual drop is more convenient for transporting, stable storage, and each dosage is consistent, has improved the effectiveness using.
The specific embodiment
Following examples are used for illustrating the present invention, but are not used for limiting the scope of the invention.If do not specialize, the conventional means that in embodiment, technological means used is well known to those skilled in the art, the raw materials used commercial goods that is.
The preparation (50000AU/ sheet) of embodiment 1 Artemisia pollen allergen vaccine sublingual lozenge
Prepare respectively Herba Artemisiae annuae pollen allergen, Artemisia, Artemisia apiacea pollen allergen, Herba artemisiae ordosicae pollen allergen and Folium et Caulis Caryopteridis pollen allergen stock solution: by machinery (vacuum cleaner), gather or five kinds of artimesias of water culture collection, cross respectively 200～300 mesh sieves and remove the impurity such as the dust in pollen, and pollen is carried out to purity detecting, and morphology and molecular biology identification.Pollen after remove impurity is used the defat of acetone soaking and stirring continuously, by the solids natural drying after defat.Take five kinds of each 100g of artimesia pollen after defat with rate of charge 1:25(g:mL) add in 50mM sodium hydrogen phosphate-phosphate sodium dihydrogen buffer solution, 4 ℃ are stirred 24h.By 8 μ m membrane filtrations for gained solution, then by filtrate successively through 0.8 μ m, 0.45 μ m, 0.22 μ m membrane filtration.Gained filtrate is with the ultrafilter membrane weighing apparatus filter of molecular cut off 5kD, until that filter liquor supernatant is the electric conductance of colourless or filter liquor is consistent with ultrafiltration buffer, obtains each allergen vaccine stock solution.With RSAT competition immunodepression, measure the activity of each vaccinogen liquid.After mixing by specific activity 1:1:1:1:1, add 4% mannitol lyophilizing, the powder (being Artemisia pollen allergen vaccine freeze-drying powder) after lyophilizing, every gram contains Artemisia pollen allergen 100,0000AU.
By following formula, supplementary material is mixed:
After above supplementary material mixes, fully stir, after mix homogeneously, 10000 of the Artemisia pollen allergen sublingual lozenge vaccines of employing direct compression legal system, every 0.1g (containing Artemisia pollen allergen 50000AU).
The preparation (5000AU/ sheet) of embodiment 2 Artemisia pollen allergen vaccine sublingual lozenges
According to the method for describing in embodiment 1, prepare Herba Artemisiae annuae pollen allergen, Artemisia, Artemisia apiacea pollen allergen, Herba artemisiae ordosicae pollen allergen and Folium et Caulis Caryopteridis pollen allergen stock solution, after mixing by specific activity 1:1:1:1:1, add 4% mannitol lyophilizing, powder (being Artemisia pollen allergen vaccine freeze-drying powder) after lyophilizing, every gram contains Artemisia pollen allergen 100000AU.
By following formula, supplementary material is mixed:
After above supplementary material mixes, fully stir, after mix homogeneously, 10000 of the Artemisia pollen allergen sublingual lozenge vaccines of employing direct compression legal system, every 0.1g (containing Artemisia pollen allergen 5000AU).
The preparation (500AU/ sheet) of embodiment 3 Artemisia pollen allergen vaccine sublingual lozenges
According to the method for describing in embodiment 1, prepare Herba Artemisiae annuae pollen allergen, Artemisia, Artemisia apiacea pollen allergen, Herba artemisiae ordosicae pollen allergen and Folium et Caulis Caryopteridis pollen allergen stock solution, after mixing by specific activity 1:1:1:1:1, add 4% mannitol lyophilizing, powder (being Artemisia pollen allergen vaccine freeze-drying powder) after lyophilizing, every gram contains Artemisia pollen allergen 10000AU.
By following formula, supplementary material is mixed:
After above supplementary material mixes, fully stir, after mix homogeneously, 10000 of the Artemisia pollen allergen sublingual lozenge vaccines of employing direct compression legal system, every 0.1g (containing Artemisia pollen allergen 500AU).
Synergism in 4 five kinds of Artemisia pollen allergen pharmacodynamicss of embodiment
1.1 animal sensitization
With reference to the people such as Hsiue TR, Int Arch Allergy Immuol1997; 112 (3): the method for describing in 295-302, is adsorbed onto 1%Al (OH) by 20mg Artemisia, Herba Artemisiae annuae pollen allergen, Artemisia apiacea pollen allergen, Herba artemisiae ordosicae pollen allergen, Folium et Caulis Caryopteridis pollen allergen mixed solution
3on gel, give Cavia porcellus subcutaneous injection 0.5ml, separately five kinds of Artemisia pollen allergen of 20mg are dissolved in to 0.1%Al (OH)
3on gel, give same guinea pig intraperitoneal injection 0.5ml.At interval of within 10 days, repeating sensitization 1 time, totally 3 times.
1.2 administering mode
Test group is divided into 8 groups: normal group, matched group, five kinds of artimesia mixing allergen administration groups, Artemisia administration group, Herba Artemisiae annuae pollen allergen administration group, Artemisia apiacea pollen allergen administration group, Herba artemisiae ordosicae pollen allergen administration group, Folium et Caulis Caryopteridis pollen allergen administration group.Normal group is in not administration of duration of test, and matched group is allergen solvent.The specification (embodiment 3) of five kinds of artimesia mixing allergen tyrosine Adjuvanted vaccines: No. 1000AU/ml(4), No. 100AU/ml(3), No. 10AU/ml(2), No. 1AU/ml(1).
Tyrosine adjuvant Artemisia vaccine, tyrosine adjuvant Herba Artemisiae annuae pollen allergen vaccine, tyrosine adjuvant Artemisia apiacea pollen allergen vaccine, tyrosine adjuvant Herba artemisiae ordosicae pollen allergen vaccine, tyrosine Folium et Caulis Caryopteridis pollen allergen vaccine specification: No. 1000AU/ml(4), No. 100AU/ml(3), No. 10AU/ml(2), No. 1AU/ml(1).Every group is cleaned 10 of level sensitized guinea pigs.
Consumption: every group of Cavia porcellus subcutaneous injection, once, administration time is 6 months altogether in injection weekly.No. 1 medicine: 1st～4 weeks, inject respectively weekly 0.1ml, 0.2ml, 0.4ml, 0.8ml.
No. 2 medicines: 5～8 weeks, inject respectively weekly 0.1ml, 0.2ml, 0.4ml, 0.8ml.No. 3 medicines: 9th～12 weeks, inject respectively weekly 0.1ml, 0.2ml, 0.4ml, 0.8ml.No. 4 medicines: 13rd～16 weeks, inject respectively weekly 0.1ml, 0.2ml, 0.4ml, 0.8ml.Since the 17th week, inject weekly medicine 1ml No. 4, to off-test.
1.3 pharmacodynamic evaluation
After administration finishes, every group of Cavia porcellus is respectively at diverse location subcutaneous injection 0.5ml100AU/ml Artemisia aqueous solution, Herba Artemisiae annuae pollen allergen aqueous solution, Artemisia apiacea pollen allergen aqueous solution, Herba artemisiae ordosicae pollen allergen aqueous solution, Folium et Caulis Caryopteridis pollen allergen aqueous solution.Measure the welt of every Cavia porcellus different injection sites generation and the diameter (meansigma methods of major diameter and minor axis diameter) of erythema, calculate the arithmetical average of every kind of pollen allergen welt of every group of Cavia porcellus and erythema diameter.The results are shown in Table 1.
Five kinds of Artemisia pollen allergen vaccines of table 1 are worked in coordination with pharmacodynamic evaluation
Note: 1 group of administration: be five kinds of Artemisia pollen allergen mixed vaccines of tyrosine adjuvant; 2 groups of administrations: be tyrosine adjuvant Artemisia epidemic disease Artemisia sieversiana Willd. pollen vaccine; 3 groups of administrations: be tyrosine adjuvant Herba Artemisiae annuae pollen allergen vaccine; 4 groups of administrations: tyrosine adjuvant Artemisia apiacea pollen allergen vaccine; 5 groups of administrations: tyrosine adjuvant Herba artemisiae ordosicae pollen allergen vaccine; 6 groups of administrations: tyrosine adjuvant Folium et Caulis Caryopteridis pollen allergen vaccine.
As known from Table 1: single tyrosine adjuvant Artemisia pollen allergen vaccine, can effectively reduce corresponding Artemisia pollen-induced degree, also can reduce other four kinds of Artemisia pollen-induced degree simultaneously, but the relative five kinds of artimesia mixing allergen vaccines of single tyrosine Artemisia pollen allergen vaccine, the significant degree of its treatment to other four kinds of Artemisia pollen-induced is not as five kinds of Artemisia pollen allergen mixing tyrosine vaccines (p < 0.01).By the result of this experiment, proved that five kinds of Artemisia pollen allergen exist intercrossing, but the also property of there are differences, the effectiveness of five kinds of Artemisia pollen allergen combined vaccines is higher than single Artemisia pollen allergen vaccine.
The detection of embodiment 5 Artemisia pollen allergen vaccine sublingual lozenge activity
Artemisia pollen allergen Sublingual drop vaccine activity detects the method for using UniCAP to adopt the experiment of RAST competitive inhibition.
50000AU/ sheet, 5000AU/ sheet, 500AU/ sheet are respectively got to 10, and with physiological saline solution, the finished product of 3 specifications and internal reference product are 10 with normal saline dilution respectively
-1, 10
-2, 10
-3, 10
-4, 10
-5totally 5 concentration, then with 100 μ l equivalent serum mix, and hatch 60min for 37 ℃, then to the upper machine testing of Artemisia apiacea pollen allergen immunoCAP, calculate suppression ratio, take the logarithm value of dilution factor 1/10 as abscissa, percent inhibition is vertical coordinate, the dilution factor while calculating 50% suppression ratio.Dilution factor by 50% suppression ratio, compared with internal reference product, calculates activity (AU).The results are shown in Table 2.
Table 2 three batch sample activity values
The investigation of embodiment 6 Artemisia pollen allergen vaccine sublingual lozenge stability
This experiment is passed through three batches of Artemisia pollen allergen vaccine sublingual lozenges 2-8 ℃ of placement, March, June, JIUYUE, December, active variation in 18 months, the stability (table 3-table 5) of investigation Artemisia pollen allergen vaccine sublingual lozenge.
Table 3201006001 batch stability experiment data
Table 4201007001 batch stability experiment data
Table 5201008001 batch stability experiment data
Above experimental result shows, Artemisia pollen allergen vaccine sublingual lozenge three batch samples are placed 18 months at 2-8 ℃, actively significantly do not change, this condition place 18 months basicly stable.
Although above the present invention is described in detail with a general description of the specific embodiments, on basis of the present invention, can make some modifications or improvements it, this will be apparent to those skilled in the art.Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, all belong to the scope of protection of present invention.
Claims (2)
1. an Artemisia pollen allergen vaccine buccal tablet, it is characterized in that, by Artemisia pollen allergen vaccine and pharmaceutically acceptable carrier, formed, wherein, the weight ratio of each component is Artemisia pollen allergen vaccine: mannitol: crosslinked Carboxymethyl cellulose sodium: anhydrous silica gel: microcrystalline Cellulose: magnesium stearate: Lactose hydrate=1:5:1:0.02:0.1:0.05:0.01;
The allergen that described Artemisia pollen allergen vaccine comprises five kinds of sensitization artimesias, five kinds of sensitization sagebrusses are: Artemisia sieversiana Willd. (Artemisia sieversiana Willd), Herba Artemisiae annuae (Artemisia annua L.), Radix Artemisia ordosicae (Artemisia argyi Levl.et Vant), Herba artemisiae ordosicae (A.ordosica krasch) and Folium et Caulis Caryopteridis (A.sphaerocep hala krasch), the allergenic activity of five kinds of sensitization artimesias is than being 1:1:1:1:1.
2. the preparation method of Artemisia pollen allergen vaccine buccal tablet described in claim 1, is characterized in that, comprises the following steps:
1) gather five kinds of artimesias, cross respectively 200～300 mesh sieves and remove the impurity in pollen;
2) pollen after remove impurity soaks with acetone, stirs defat, dry;
3) by the pollen after defat respectively with 1:10～50(g:mL) rate of charge add in sodium hydrogen phosphate-phosphate sodium dihydrogen buffer solution of 50～500mM, 4 ℃ stir 4～24h;
4) by gained solution in step 3) successively through 8 μ m, 0.8 μ m, 0.45 μ m and 0.22 μ m membrane filtration;
5) the ultrafilter membrane weighing apparatus filter with molecular cut off 5kD by gained filtrate in step 4), until that filter liquor supernatant is the electrical conductivity of colourless or filter liquor is consistent with ultrafiltration buffer used, obtains each allergen vaccine stock solution;
6) with RSAT competition immunodepression, measure the activity of each vaccinogen liquid, be then mixed in proportion each vaccinogen liquid, obtain Artemisia pollen allergen vaccine;
7) to adding lyophilizing after mannitol in Artemisia pollen allergen vaccine;
8) powder after Artemisia pollen allergen vaccine freeze-drying and crosslinked Carboxymethyl cellulose sodium, anhydrous silica gel, microcrystalline Cellulose, magnesium stearate and Lactose hydrate being mixed in proportion to rear tabletting makes.
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| CN106967696B (en) * | 2017-02-22 | 2020-01-14 | 杭州艾乐吉生物科技有限公司 | Allergen of artemisia pollen and application thereof |
| CN111175512A (en) * | 2018-11-09 | 2020-05-19 | 北京新华联协和药业有限责任公司 | Preparation and test of artemisia pollen specific IgE antibody standard serum |
| CN114053402A (en) * | 2020-08-03 | 2022-02-18 | 格林生物医药科技(天津)有限公司 | Allergen preparation |
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