CN111904970A - Application of pulsatilla chinensis saponin B4 in preparation of medicine for treating asthma - Google Patents
Application of pulsatilla chinensis saponin B4 in preparation of medicine for treating asthma Download PDFInfo
- Publication number
- CN111904970A CN111904970A CN202010836864.2A CN202010836864A CN111904970A CN 111904970 A CN111904970 A CN 111904970A CN 202010836864 A CN202010836864 A CN 202010836864A CN 111904970 A CN111904970 A CN 111904970A
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- Prior art keywords
- saponin
- spray
- aerosol
- changed
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Links
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
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Abstract
The invention discloses application of pulsatilla chinensis saponin B4 in preparing a medicament for treating asthma of mammals including human beings. The invention has high bioavailability, quick effect, direct action on focus and good curative effect on asthma.
Description
Technical Field
The invention relates to the technical field of medicines. More specifically, the invention relates to application of pulsatilla saponin B4 in preparing a medicine for treating asthma.
Background
Pulsatillae radix is dried root of Pulsatilla chinensis (Bunge) Regel of Pulsatilla of Ranunculaceae, and has effects of clearing heat and detoxicating, cooling blood and relieving dysentery. Modern pharmacological studies show that the saponins in pulsatilla chinensis is the main active component of pulsatilla chinensis, and has the effects of enhancing immune function, resisting inflammation and the like. Pulsatillae saponin B4 is pentacyclic triterpenoid saponin extracted from Pulsatillae radix and has pharmacological effects of resisting inflammation, bacteria and virus, regulating immunity, resisting tumor, oxidation and virus, but Pulsatillae saponin B4 has no reported effect on treating asthma.
Disclosure of Invention
An object of the present invention is to solve at least the above problems and to provide at least the advantages described later.
The invention also aims to provide the application of the pulsatilla saponin B4 in preparing the medicine for treating asthma, which has high bioavailability and quick response, can directly act on focus and has good curative effect on asthma.
To achieve these objects and other advantages in accordance with the present invention, there is provided a use of pulsatillae radix saponin B4 in the manufacture of a medicament for treating asthma in a mammal including a human.
Preferably, the medicament contains effective amount of pulsatilla saponin B4 and pharmaceutically acceptable carrier.
Preferably, the medicament is formulated into a pharmaceutically acceptable dosage form.
Preferably, the medicament is formulated as an aerosol.
Preferably, the medicament is formulated as a spray.
Preferably, the dosage of the pulsatilla saponin B4 is not less than 10 mg/kg-d.
The invention at least comprises the following beneficial effects:
first, anemonin B4 has the effect of treating asthma, and its action mechanism may be related to the reduction of the level of blood, alveolar lavage fluid and lung tissue inflammatory factors such as IL-6, TNF-alpha, and the reduction of the level of White Blood Cells (WBC), Lymphocytes (LYMPH) and Neutrophils (NEUT). The treatment effect of the pulmonioside B4 aerosol and the spray on rat bronchial asthma induced by OVA is stronger than that of pulmonioside B4 for injection, and the dosage is less than that of pulmonioside B4 for injection, which shows that the pulmonioside B4 aerosol and the spray have more remarkable treatment effect on asthma than that of pulmonioside B4 for injection;
secondly, as the aerosol and the spraying agent have the advantages of small dosage, uniform distribution, quick response, high bioavailability, convenient use and the like, are suitable for asthma, can directly reach the focus, and reduce the side effect of the gastrointestinal tract, the invention provides scientific basis for preventing and treating the upper respiratory tract infection diseases such as asthma and the like by the following Chinese pulsatilla saponin B4 aerosol and spraying agent, so as to better serve the clinic.
Additional advantages, objects, and features of the invention will be set forth in part in the description which follows and in part will become apparent to those having ordinary skill in the art upon examination of the following or may be learned from practice of the invention.
Detailed Description
The present invention is further described in detail below with reference to examples to enable those skilled in the art to practice the invention with reference to the description.
It will be understood that terms such as "having," "including," and "comprising," as used herein, do not preclude the presence or addition of one or more other elements or groups thereof.
It is to be noted that the experimental methods described in the following embodiments are all conventional methods unless otherwise specified, and the reagents and materials are commercially available unless otherwise specified.
Use of pasqueflower saponin B4 in the manufacture of a medicament for the treatment of asthma in a mammal, including a human.
The pharmaceutical preparation contains the pulsatilla saponin B4 with effective treatment amount, and the rest is pharmaceutically acceptable carriers and excipients which are nontoxic and inert to human and animals.
The pharmaceutically acceptable carrier or excipient is one or more selected from solid, semi-solid and liquid diluents, fillers and pharmaceutical adjuvants. The pharmaceutical preparation of the present invention is used in the form of a dose per unit body weight. The extract of the present invention can be administered to a patient in need of treatment by oral administration or injection. For oral administration, it can be made into tablet, sustained release tablet, controlled release tablet, capsule, dripping pill, pellet, suspension, emulsion, powder or granule (nanometer preparation), oral liquid, etc.; for injection, the composition can be made into sterilized aqueous or oily solution, sterile powder for injection, liposome or emulsion.
For example, when the compound aerosol is prepared, besides the proper propellant, the proper additive is selected mainly according to the physicochemical properties of the medicine to prepare the aerosol of a certain type so as to meet the requirements of clinical medication. The aerosol excipient mainly comprises a latent solvent and a propellant, wherein the latent solvent is glycerol, propylene glycol, ethanol, water or an ethanol-water mixed system, and the propellant mainly comprises trichloromonofluoromethane (F11), dichlorodifluoromethane (F12), dichlorotetrafluoroethane (F114) or a mixture of any two of the trichloromonofluoromethane, the dichlorodifluoromethane and the propellant. In addition, the aerosol can be added with surfactant, cosolvent, suspending agent, antioxidant, etc. to optimize the aerosol prescription. The pulsatilla saponin B4 aerosol is mainly used for inhalation therapy and is prepared into solution type aerosol, so clarity and mouthfeel comfort are mainly considered in prescription design.
For example, when the spray is prepared, ethanol, glycerol, water, propylene glycol or a mixture thereof is selected as a solvent; the fatty acid sorbitan substance, the polysorbate substance, the polyoxyethylene fatty alcohol ether substance, the polyoxyethylene-polyoxypropylene copolymer, the polyethylene glycol substance, the cyclodextrin substance, the sodium dodecyl sulfate, the cetyl trimethyl ammonium bromide or the mixture thereof is taken as a solubilizer; sodium dodecyl sulfate, laurocapram, lauric acid, sodium laurate, lecithin, oleic acid, poloxamer, choline phosphate, etc. or a mixture thereof as absorption enhancer. The pulsatilla saponin B4 spray is mainly used for inhalation or spray therapy and is prepared into a solution type spray, so clarity and comfortable mouthfeel are mainly considered in prescription design.
< example 1>
The preparation method of the pulsatilla chinensis saponin B4 aerosol comprises the following steps: collecting Pulsatillae saponin B4, 100g, 60% medicinal ethanol 1000g, and F111000g, dissolving Pulsatillae saponin B4 with 60% ethanol under reflux, standing at cold place for 48h, filtering, supplementing the filtrate with 60% ethanol to 1000mL, subpackaging into 200 bottles with 5mL each, and pressing propellant F11And (6) sealing the cover.
The aerosol prepared in example 1 is colorless, clear and transparent, has a pH of 7.52, has a total number of puffs per bottle of 500 times, has an average value of 10 puffs of 0.092mL per puff, accounts for 92% of the indicated puffs, contains 9.81mg of the main drug per puff, mostly has a particle size of 5 μm or less, and is subjected to stability test by a constant temperature acceleration test method, wherein the aerosol can stably exist after being placed at a high temperature (40 ℃) for 10 days (the pH is changed from 7.52 to 7.48, and the content is changed from 9.1% to 9.6%), the anemonin B4 aerosol can stably exist after being placed at a low temperature (-18 ℃) for 10 days (the pH is changed from 7.52 to 7.48, and the content is changed from 9.1% to 9.6%), and only the content is reduced after being placed at a low temperature (4500 ± 500Lx) for 10 days (the pH is changed from 7.52 to 7.56, and the content is changed from 10% to 9.7%), and a proper device should be kept in a dark place.
< example 2>
The preparation method of the pulsatilla chinensis saponin B4 aerosol comprises the following steps: taking out whitePulsatillae saponin B4, 50g, borneol 5mg, vitamin C1g, medicinal ethanol 8g, 60% ethanol 990g, F121000 g. Dissolving Borneolum in medicinal ethanol, slowly adding 60% ethanol into Borneolum solution, adding radix Pulsatillae saponin B4 and vitamin C, heating in water bath, stirring to dissolve, standing at cold place for 48 hr, filtering, adding 60% ethanol to 1000mL, bottling in 200 bottles (5 mL each), and pressing F12And (6) sealing the cover.
The aerosol prepared in example 2 is colorless, clear and transparent, has a pH of 7.12, has a total number of puffs per bottle of 500 times, has a volume of 0.095mL per puff, accounting for 95% of the indicated puffs, contains 4.73mg of the main drug per puff, mostly has a particle size of 5 μm or less, and is subjected to stability test by a constant temperature acceleration test method, and can stably exist after being placed at a high temperature (40 ℃) for 10 days (the pH changes from 7.12 to 7.09, and the content changes from 4.94% to 4.95%), can stably exist after being placed at a low temperature (-18 ℃) for 10 days (the pH changes from 7.12 to 7.13, and the content changes from 4.91% to 4.92%), and only shows a decrease after being placed at a low temperature (-18 ℃) for 10 days (the pH changes from 7.12 to 7.19, and the content changes from 5.0% to 4.75%), and thus should be stored in a suitable dark place.
< example 3>
The preparation method of the pulsatilla chinensis saponin B4 aerosol comprises the following steps: taking pulsatilla chinensis saponin B4, 10g, sodium metabisulfite 1g, water 999g and F12:F111000g of mixed propellant at 3: 7. Dissolving anemonin B4 and sodium pyrosulfite in water, heating to dissolve, cooling at room temperature, standing at cold place for 48h, filtering, adding 1000mL of water to the filtrate, packaging into 200 bottles, each bottle containing 5mL, pressing propellant, and sealing.
The aerosol prepared in example 3 is colorless, clear and transparent, has a pH of 7.14, has a total number of puffs per bottle of 500 times, has a volume of 0.098mL per puff, which is calculated as an average of 10 puffs, and accounts for 98% of the indicated puffs, contains 0.98mg of the main drug per puff, mostly has a particle size of 5 μm or less, and is subjected to stability test by a constant temperature acceleration test method, and is stable after being placed at a high temperature (40 ℃) for 10 days (the pH is changed from 7.14 to 7.09, and the content is changed from 0.98% to 0.99%), and stable after being placed at a low temperature (-18 ℃) for 10 days (the pH is changed from 7.14 to 7.15, and the content is changed from 0.98% to 0.99%), and is reduced only after being placed at a low temperature (4500 ± 500Lx) for 10 days (the pH is changed from 7.14 to 7.19, and the content is changed from 1.00% to 0.92%), and therefore, a suitable device and a light-shielding device should be adopted.
< example 4>
The preparation method of the pulsatilla chinensis saponin B4 aerosol comprises the following steps: collecting radix Pulsatillae saponin B4, 40g, Borneolum 20mg, 80% ethanol 1000g, and F1141200 g. Dissolving Borneolum Syntheticum with 80% ethanol, adding pulsatilla saponin B4, stirring to dissolve completely, standing at cold place for 48h, filtering, adding 80% ethanol to 1000mL of filtrate, bottling in 200 bottles, each bottle having 5mL, and pressing F114And (6) sealing the cover.
The aerosol prepared in example 4 is colorless, clear and transparent, has a pH of 7.48, has a total number of puffs per bottle of 500 times, has an average value of 10 puffs of 0.090mL per puff, accounts for 90% of the indicated puffs, contains 3.56mg of the main drug per puff, mostly has a particle size of 5 μm or less, and is subjected to stability test by a constant temperature acceleration test method, and can stably exist after being placed at a high temperature (40 ℃) for 10 days (the pH is changed from 7.48 to 7.43, and the content is changed from 3.95% to 3.96%), can stably exist after being placed at a low temperature (-18 ℃) for 10 days (the pH is changed from 7.48 to 7.48, and the content is changed from 3.92% to 3.95%), and only has a decrease after being placed at a low temperature (4500 ± 500Lx) for 10 days (the pH is changed from 7.48 to 7.57, and the content is changed from 4.00% to 3.82%), and therefore, a suitable device and a dark device should be adopted for storage.
< example 5>
The preparation method of the pulsatilla chinensis saponin B4 aerosol comprises the following steps: collecting Pulsatillae saponin B4, 80g, 30% ethanol 1000g, and F121000 g. Dissolving Pulsatillae saponin B4 with 30% ethanol, standing in cold place for 48h, filtering, adding 30% ethanol to 1000mL of filtrate, packaging into 200 bottles with 5mL each, and pressing F12And (6) sealing the cover.
The aerosol prepared in example 5 is colorless, clear and transparent, has a pH of 7.36, has a total number of puffs per bottle of 500 times, has a volume of 0.091mL per puff, which is 91% of the indicated puff volume, contains 7.12mg of the main drug per puff, mostly has a particle size of 5 μm or less, and is subjected to stability test by a constant temperature acceleration test method, wherein the aerosol can stably exist after being placed at a high temperature (40 ℃) for 10 days (the pH changes from 7.36 to 7.32, and the content changes from 7.98% to 7.94%), the aerosol can stably exist after being placed at a low temperature (-18 ℃) for 10 days (the pH changes from 7.36 to 7.35, and the content changes from 7.93% to 7.91%), and only after being placed at a low temperature (4500 ± 500Lx) for 10 days (the pH changes from 7.36 to 7.41, and the content changes from 8.00% to 7.82%), so that a proper light-shielding device and a light-shielding device should be adopted.
< example 6>
The preparation method of the pulsatilla chinensis saponin B4 spray comprises the following steps: taking and adding the pulsatilla chinensis saponin B4, 5g, 10mL of propylene glycol, 80 of polysorbate, 0.75mL and 20% ethanol to 100 mL. Adding pulsatilla chinensis saponin B4 into polysorbate 80, stirring, adding 20% ethanol to a sufficient amount, stirring with a homogenizer, and quantitatively packaging into a spray container to obtain the final product. When in use, the spray is directly sprayed into the oral cavity, and 1-3 sprays are carried out at a time.
The spray prepared in example 6 is colorless, clear and transparent, has a pH of 7.02, has a total number of puffs per bottle of 500 times, has a spraying amount of 0.095mL per puff, accounting for 95% of the indicated spraying amount, contains 9.75mg of the main drug per puff, mostly has a particle size of 5 μm or less, and is subjected to stability test by a constant temperature accelerated test method, and is reduced in content (the pH is changed from 7.02 to 7.06, and the content is changed from 5.0% to 4.96%) after being placed under illumination (4500 ± 500Lx) for 10 days, and is stable (the pH is changed from 7.02 to 7.03, and the content is changed from 4.92% to 4.98%) after being placed under low temperature (-18 ℃) for 10 days, and is stable (the pH is changed from 7.02 to 7.00, and the content is changed from 4.91% to 4.84%) after being placed under high temperature (-40 ℃) conditions for 10 days, so that the spray should be preserved at a proper temperature to avoid high temperature.
< example 7>
The preparation method of the pulsatilla chinensis saponin B4 spray comprises the following steps: taking anemonin B4, 5g, 15mL of absolute ethyl alcohol and 40065 mL of polyethylene glycol, and adding water to 100 mL. Weighing the pulsatilla chinensis saponin B4 according to the proportion, dissolving the pulsatilla chinensis saponin B4 in absolute ethyl alcohol and polyethylene glycol 400, uniformly stirring, adding water to a sufficient amount, uniformly stirring by using a homogenizer, and quantitatively filling into a spray container to obtain a finished product. When in use, the spray is directly sprayed into the oral cavity, and 1-3 sprays are carried out at a time.
The spray prepared in example 7 is colorless, clear and transparent, has a pH of 7.13, has a total number of puffs per bottle of 500 times, has a spraying amount of 0.095mL per puff, accounting for 95% of the indicated spraying amount, contains 9.5mg of the main drug per puff, mostly has a particle size below 5 particles, and is subjected to stability test by a constant temperature accelerated test method, wherein the content of the spray is reduced after the spray is placed under illumination (4500 ± 500Lx) for 10 days (the pH is changed from 7.13 to 7.17, and the content is changed from 5.0% to 4.98%), and the spray can be stably stored under low temperature (-18 ℃) for 10 days (the pH is changed from 7.13 to 7.14, and the content is changed from 4.92% to 4.96%), and the spray can be stably stored under appropriate temperature only after the spray is placed under high temperature (40 ℃) for 10 days (the pH is changed from 7.13 to 7.08, and the content is changed from 4.95% to 4.84%).
< example 8>
The preparation method of the pulsatilla chinensis saponin B4 spray comprises the following steps: adding pulsatilla chinensis saponin B4, 1g, poloxamer 1885 g and 35% ethanol to 100 mL. Weighing the pulsatilla chinensis saponin B4 and the poloxamer according to the proportion, dissolving in 35% ethanol, stirring uniformly by using a homogenizer, and quantitatively filling into a spray container to obtain a finished product. When in use, the spray is directly sprayed into the oral cavity, and 1-5 sprays are carried out at a time.
The spray prepared in example 8 is colorless, clear and transparent, has a pH of 7.05, has a total number of puffs per bottle of 500 times, has a spraying amount of 0.095mL per puff, accounting for 95% of the indicated spraying amount, contains 1.9mg of the main drug per puff, has a particle size mostly below 5 drugs, and is subjected to stability test by a constant temperature acceleration test method, wherein the content of the spray is reduced after the spray is placed under illumination (4500 ± 500Lx) for 10 days (the pH is changed from 7.05 to 7.13, and the content is changed from 100% to 96%), the spray can be stably stored under low temperature (-18 ℃) for 10 days (the pH is changed from 7.05 to 7.12, and the content is changed from 98% to 98%), and the spray can be stably stored under appropriate temperature only after the spray is placed under high temperature (40 ℃) for 10 days (the pH is changed from 7.05 to 7.11, and the content is changed from 98% to 89%), so that high temperature is avoided.
< example 9>
The preparation method of the pulsatilla chinensis saponin B4 spray comprises the following steps: adding 1g of pulsatilla chinensis saponin B4, 2g of sodium dodecyl sulfate and 50% ethanol to 100 mL. Weighing the pulsatilla chinensis saponin B4 and the sodium dodecyl sulfate according to the proportion, dissolving in 50% ethanol, stirring uniformly by using a homogenizer, and quantitatively filling into a spray container to obtain a finished product. When in use, the spray is directly sprayed into the oral cavity, and 1-3 sprays are carried out at a time.
The spray prepared in example 9 is colorless, clear and transparent, has a pH of 7.18, has a total number of puffs per bottle of 500 times, has a puff volume of 0.095mL as an average of 10 puffs, accounts for 95% of the indicated puff volume, has a primary drug content of 1.96mg per puff, has a particle size mostly below 5 particles, and is subjected to stability test by a constant temperature acceleration test method, wherein the spray is reduced in content (the pH is changed from 7.18 to 7.14, and the content is changed from 100% to 98%) after being placed under illumination (4500 using the constant temperature acceleration test) for 10 days, and can be stably stored (the pH is changed from 7.18 to 7.18, and the content is changed from 97% to 96%) after being placed under a low temperature (-18 ℃) for 10 days, and can be stored at a proper temperature to avoid high temperature (the pH is changed from 7.18 to 7.14, and the content is changed from 98% to 90%).
< example 10>
The preparation method of the pulsatilla chinensis saponin B4 spray comprises the following steps: adding 1g of pulsatilla chinensis saponin B4, 1g of hydroxypropyl-beta-cyclodextrin, 1g of sorbitan monostearate (Span 60) and 60% ethanol to 100 mL. Weighing the pulsatilla chinensis saponin B4 and the hardy pear tanan according to the proportion, dissolving in 60% ethanol, stirring uniformly by a high-speed homogenizer, and quantitatively filling into a spray container to obtain a finished product. When in use, the spray is directly sprayed into the oral cavity, and 1-5 sprays are carried out at a time.
The spray prepared in example 10 is colorless, clear and transparent, has a pH of 7.16, has a total number of puffs per bottle of 500 times, has a puff volume of 0.095mL as an average of 10 puffs, accounts for 95% of the indicated puff volume, contains 1.96mg of the main drug per puff, mostly has a particle size below 5 particles, and is subjected to stability test by a constant temperature acceleration test method, wherein the content of the spray decreases after being placed under illumination (4500 using the constant temperature acceleration test) for 10 days (pH changes from 7.16 to 7.19, and content changes from 100% to 96%), the spray can stably exist after being placed under low temperature (-18 ℃) for 10 days (pH changes from 7.16 to 7.19, and content changes from 95% to 94%), and the spray can stably exist only after being placed under high temperature (40 ℃) for 10 days (pH changes from 7.16 to 7.11, and content changes from 98% to 92%), so that high temperature should be preserved to avoid high temperature.
1. Material
1.1 Experimental animals
The species are as follows: brown Norway rat, grade: SPF grade, number of pre-purchased animals and sex: 104, males. Age: 6 to 7 weeks old when purchased and 7 to 8 weeks old when the test started. Weight: the weight average number of the purchased product is 180-200g, and the weight average number of the purchased product is 220-240 g. The source is as follows: beijing Weitonglihua laboratory animal technology Co., Ltd, production license number: SCXK (Kyoto) 2016-. Animal welfare: this organization was certified by AAALAC (the international committee for laboratory animal evaluation and management). The test has been approved by the IACUC (committee for the management and use of laboratory animals), approval serial No.: IACUC-A2019175-P002-01. And (3) treating the rest animals: after the experiment is finished, if the residual animals exist, the experimental animal management part is handed over.
1.2 drugs and reagents
Pulsatillae saponin B4 (Jiangxi Bencao Tian Gong Tech Co., Ltd., 2019030101); ovalbumin (Ovalbumin, OVA, Sigma Aldrich, SLBV 6597); aluminum hydroxide gel (aluminum hydroxide gel, InvivoGen, 5594); pertussis Toxin (Pertussis Toxin, PTX, List Biological laboratories inc).
1.3 animal groups
Group design: experimental design 13 groups: a blank control group, a model control group, a pulsatilla saponin B4(10mg/kg) caudal vein group, a pulsatilla saponin B4 aerosol group (examples 1-5 groups), and a pulsatilla saponin B4 spray group (examples 6-10 groups). Animal number and sex: each group had 8 males. The grouping method comprises the following steps: groups were randomized according to rat body weight using the PRISTIMA version 7.2.0 data system.
1.4 Molding method
According to the previous research results of the mechanism, the experiment is supposed to adopt 1 mL/OVA subcutaneous injection for split injection, and simultaneously adopts 0.5mL of 0.1 mu g/mL PTX for intraperitoneal injection for sensitization (D1), and after 7 days, the same operation is carried out for intensifying sensitization (D8); after 7 days of the last sensitization, 0.1mg/mL OVA was injected via trachea for 2 times (D15, D22) to perform molding.
1.4.1 sensitization
Sensitization route: subcutaneous injection (OVA emulsion) and intraperitoneal injection (PTX); sensitization frequency: 2-time, D1 and D8 sensitization method: each group of rats was administered with OVA emulsion or physiological saline at a concentration corresponding to the subcutaneous injection (about 200. mu.L each in 5-point injection, about 0.2 mL/point, subcutaneous injection in both feet, subcutaneous injection in both inguinal regions, and intraperitoneal injection) in Table 2, and then 0.1. mu.g/mL of PTX or DPBS was administered in intraperitoneal injection (i.p.) at 0.5 mL.
1.4.2OVA excitation
Excitation pathway: intratracheal instillation excitation frequency: d15 and D22. The excitation method comprises the following steps: after anesthetizing the rats with 2% -5% isoflurane each time at a similar time point, the rats were vertically fixed and administered by slowly dropping 0.25mL of 1mg/mL OVA or DPBS into the trachea with a syringe (smooth and near spherical needle tip) under the guidance of an optical fiber. The supine position is maintained until consciousness is completely restored and then the supine position is returned to the cage.
1.4.3 dose design and basis
According to the previous research results, the dosage of the pulsatilla saponin B4 tail vein group administration medicine in the test is 10 mg/kg. Pulsatillae saponin B4 aerosol group (example 1-5 groups), and Pulsatillae saponin aerosol obtained according to the above formulation was administered 1mL each time and once a day. Pulsatillae saponin B4 spray group (example 6-10 groups), 1mL each time, twice daily. The blank and model controls were given an equal volume of 0.9% sodium chloride solution. Frequency and period of administration: administration was started on the day of the second sensitization (before sensitization), 1 time/day, for 14 consecutive days. The Day of first sensitization was defined as Day 1 of the experiment, Day 1 (D1).
1.4.4 statistics of data
Firstly, LEVENE test is adopted to carry out homogeneity of variance test, and when the variances are uniform (P is more than 0.05), single-factor analysis of variance (ANOVA) is adopted to carry out statistical test; when the variance is not uniform (P is less than 0.05), statistical analysis is performed by Kruskal-Wallis H rank sum test (K-W method). When the single-factor variance analysis shows that the difference has statistical significance (P is less than or equal to 0.05), the LSD method is adopted for statistical analysis; when one-way anova showed that the difference was not statistically significant (P >0.05), then the statistical analysis was complete. When the Kruskal-Wallis H rank sum test shows that the difference is statistically significant (P is less than or equal to 0.05), the Mann-Whitney U test (M-W method) is adopted to compare the difference among the groups; statistical analysis was concluded when Kruskal-Wallis H rank sum test showed no statistical significance for the difference (P > 0.05).
2. Results and discussion
2.1 Effect of Pulsatillae saponin B4 on IL-6, TNF-alpha levels in lung tissue homogenates
Compared with a blank control group, the levels of IL-6 and TNF-in the lung tissues of rats in the model control group are obviously increased (P < 0.001); compared with the model control group, the levels of IL-6 and TNF-tissues in the lung tissues of rats in the tail vein group, the aerosol group and the spray group are obviously reduced (P <0.001 or P <0.05), and the effects of the aerosol group and the spray group are better than those of the tail vein injection group, which is detailed in table 1.
TABLE 1
Comparing with model group, P <0.05, P <0.01, P <0.001
2.2 Effect of Pulsatillae saponin B4 on IL-6, TNF-Wash content in alveolar lavage fluid (BALF)
Compared with a blank control group, the level of the alveolar lavage fluid IL-6 and TNF-fluid of the rats in the model control group is obviously increased (P < 0.001); compared with the model control group, the levels of IL-6 and TNF-tissue in the lung tissues of rats in the tail vein group, the aerosol group and the spray group are obviously reduced (P is less than 0.001 or less than 0.05), and the effects of the aerosol group and the spray group are better than those of the tail vein injection group, which is detailed in table 2.
TABLE 2
Comparing with model group, P <0.05, P <0.01, P <0.001
2.3 Effect of anemonin B4 on the content of IL-6 and TNF-glycosides in serum
Compared with a blank control group, the serum IL-6 and TNF-mouse level of the rat of the model control group is obviously increased (P < 0.01); compared with the model control group, the levels of IL-6 and TNF-tissues in the lung tissues of rats in the tail vein group, the aerosol group and the spray group are obviously reduced (P <0.001 or P <0.05), and the effects of the aerosol group and the spray group are better than those of the tail vein injection group, which is detailed in table 3.
TABLE 3
Note: comparing with model group, P <0.05, P <0.01, P <0.001
2.4 Effect of Pulsatillae saponin B4 on blood general index
Compared with a blank control group, the level of blood WBC, NEUT and LYMPH of the rats in the model control group is obviously increased (P < 0.01); compared with the model control group, the blood WBC, NEUT and LYMPH levels of the rats in the tail vein group, the aerosol group and the spray group are all obviously reduced (P is less than 0.05 or P is less than 0.01), and the effects of the aerosol group and the spray group are better than those of the tail vein injection group, which is detailed in Table 4.
TABLE 4
3. Conclusion
The root cause of asthma is bronchitis, which belongs to nonspecific inflammation, and the nonspecific inflammation is mostly caused by infection and turns into asthma after long-term effective treatment. Furthermore, asthma is a chronic airway inflammation involving a variety of cells, particularly mast cells, eosinophils and T lymphocytes, and thus detection of the inflammatory factors IL-6, TNF-6 and WBC, LYMPH, NEUT levels is directly linked to asthma, and reduction of these indices can reflect therapeutic effects on asthma. The experimental result shows that the anemonin B4 aerosol and spray has the effect of treating asthma, and the action mechanism of the anemonin B4 aerosol and spray is probably related to reducing the level of blood, alveolar lavage fluid and lung tissue inflammatory factors such as IL-6 and TNF-asthma, and reducing the level of White Blood Cells (WBC), Lymphocytes (LYMPH) and neutrophilic granulocytes (NEUT) in the blood. The pulmonioside B4 aerosol and spray have stronger treatment effect on rat bronchial asthma induced by OVA than pulmonioside B4 for injection and the dosage is less than pulmonioside B4 for injection, which shows that pulmonioside B4 aerosol and spray have more obvious asthma treatment effect than pulmonioside B4 for injection.
The number of apparatuses and the scale of the process described herein are intended to simplify the description of the present invention. Applications, modifications and variations of the present invention will be apparent to those skilled in the art.
While embodiments of the invention have been described above, it is not limited to the applications set forth in the description and the embodiments, which are fully applicable to various fields of endeavor for which the invention may be embodied with additional modifications as would be readily apparent to those skilled in the art, and the invention is therefore not limited to the details given herein and to the examples shown and described without departing from the generic concept as defined by the claims and their equivalents.
Claims (6)
1. Use of pasqueflower saponin B4 in the manufacture of a medicament for the treatment of asthma in a mammal, including a human.
2. The use of claim 1, wherein the medicament comprises a therapeutically effective amount of pasqueflower saponin B4 and a pharmaceutically acceptable carrier.
3. The use of claim 2, wherein the medicament is formulated into a pharmaceutically acceptable dosage form.
4. The use of claim 3, wherein the medicament is formulated as an aerosol.
5. The use according to claim 3, wherein the medicament is formulated as a spray.
6. The use according to claim 1, wherein the pulsatillae radix saponin B4 is administered in an amount of not less than 10 mg/kg-d.
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