CN105640975B - Medicine for treating asthma - Google Patents
Medicine for treating asthma Download PDFInfo
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- CN105640975B CN105640975B CN201610085553.0A CN201610085553A CN105640975B CN 105640975 B CN105640975 B CN 105640975B CN 201610085553 A CN201610085553 A CN 201610085553A CN 105640975 B CN105640975 B CN 105640975B
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- 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
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
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Abstract
The invention discloses a medicine for treating asthma, which contains secologanin oxide. The medicament for treating asthma may further comprise an additional therapeutic agent. The medicine for treating asthma also contains a pharmaceutically acceptable carrier. The medicine for treating asthma is oral preparation, inhalant or injection. The oral preparation is powder, tablet, granule, capsule, solution, emulsion or suspension. The medicine has the beneficial effects of preventing asthma attack or relieving symptoms in acute attack by inhibiting the release of inflammatory factor leukotriene.
Description
Technical Field
The invention belongs to the technical field of asthma treatment, and particularly relates to a medicine for treating asthma.
Background
Bronchial asthma (asthma for short) is a chronic inflammatory disease of airways with complex pathogenesis, which is mainly clinically manifested by symptoms of recurrent wheezing, shortness of breath, chest distress, cough and the like, a few patients can also have chest pain and the like, and severe patients can have dyspnea and sudden death. Bronchial asthma is one of the most common chronic diseases worldwide, and the prevalence rate is on the increasing trend year by year in recent years. The pathogenesis of asthma is complex, no complete radical treatment method exists at present, and the existing medicine has limited treatment effect, so that the development of a new medicine for treating asthma has great significance.
Leukotrienes (LTs) are important inflammatory mediators in the pathogenesis of bronchial asthma, participate in the chronic inflammatory process of the airways, promote the accumulation of inflammatory cells in the airways, cause the contraction of airway smooth muscle, the increase of mucus secretion and the increase of vascular permeability, promote the airway remodeling and cause the airway hyperresponsiveness. 5-lipoxygenase (5-LOX) is a key enzyme in the process of LTs generation, can regulate and control the process of producing LTs by arachidonic acid through a 5-LOX pathway, and has important significance in research of asthma pathogenesis and treatment. The 5-LOX inhibitor can be used as a substitute drug for mild asthma and a combined treatment drug for moderate asthma, so as to reduce the use amount of inhaled hormone of a patient and improve the clinical curative effect of the inhaled hormone. Zileuton (Zileuton) is the only 5-LOX inhibitor approved by FDA to enter clinic at present, and the development of a novel 5-LOX inhibitor medicine for treating asthma has wide application prospect.
Disclosure of Invention
The invention aims to provide a medicament for treating asthma.
The technical scheme for solving the technical problems is as follows: a medicine for treating asthma contains secologanin oxide.
The medicament for treating asthma of the present invention as described above preferably further comprises an additional therapeutic agent.
The medicament for treating asthma, which is disclosed by the invention, preferably further comprises a pharmaceutically acceptable carrier.
The medicament for treating asthma of the present invention as described above is preferably an oral agent, an inhalant or an injection.
The medicine for treating asthma according to the present invention is preferably a powder, tablet, granule, capsule, solution, emulsion or suspension.
The invention has the beneficial effects that: by inhibiting the release of inflammatory factor leukotriene, asthma attack is prevented, or acute attack symptom is relieved.
Detailed Description
Embodiments of the present invention will be described in detail with reference to examples, in which specific conditions are not specified, according to conventional conditions or conditions recommended by manufacturers. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products commercially available.
Secologanin is an iridoid glycoside compound extracted from flos Lonicerae (Lonicera Japonica) of Caprifoliaceae, and has antioxidant and other physiological activities. No research is available on the application of secologanin oxide in the aspect of resisting asthma.
And (3) tablet preparation: 500g of secoisolaricoside, 50g of starch, 7.5g of sodium carboxymethyl starch, 0.8g of talcum powder, 50g of dextrin, 0.8g of magnesium stearate and a proper amount of 10% starch slurry, and the mixture is prepared into 1000 tablets, 3 times a day and 1 granule each time.
Granules: 500g of secoisolaricoside, 1000g of cane sugar and 500g of dextrin, and the mixture is prepared into 1000 bags, 3 times a day, and 1 bag each time.
And (3) capsule preparation: 500g of secoisolaricoside, 32g of starch, 6g of low-substituted hydroxypropyl cellulose, 4.5g of aerosil, 1.5g of magnesium stearate and a proper amount of 10% starch slurry, and the mixture is prepared into 1000 granules, 3 times a day and 1 granule each time.
Inhalation: 600g of secologanin oxide, 1000g of dichlorodifluoromethane, 320g of pure water and 8080g of polysorbate are prepared into 1000 bottles, and the administration is carried out 2-3 times a day during prevention, 1 lifting is carried out each time, the administration is carried out during attack until the symptom is relieved, and the interval of each lifting is more than 30 s. Inhalants are the most preferred dosage form of drugs for the treatment of asthma.
Injection preparation: 160g of secoisolaricoside, 2g of sodium bisulfite and water for injection are added to 1000mL, and the mixture is filled into 1000 ampoule bottles after filtration and sterilization, and is aseptically encapsulated, 1 time per day and 1 to 5 per time, and is at least diluted to 200mL of 0.9 percent sodium chloride or 5 percent glucose injection for intravenous drip.
Example 1 inhibitory Activity of secologenin on 5-lipoxygenase (5-LOX)
1.1 Experimental materials
Reagent: recombinant human 5-lipoxygenase (humanrecombinant5-LOX) (cayman, cat60402), arachidonic acid (cayman, cat90010), H2DCFDA(sigma，catD6883)，NDGA(cayman，cat70300)，Tris(biocam，cat0479)，CaCl2(Nanjing chemical Co., Ltd.), Na2ATP (sigma, catA2383), secologlycoside (Shanghai Fengshou reagent Co., Ltd.), DMSO (sigma, D2650), Milli-QH2O。
Instrument enzyme mark instrument (molecular apparatus spectrum MaxM2e), liquid-transfering gun (eppendorf), micro-oscillator (Guohua ZW-A), electrothermal constant-temperature air-blast drying cabinet (Shanghai sperm macro DHG-9023), -70 deg.C refrigerator (HaierDW-86L286 type), -20 deg.C refrigerator (SIMENSBCD-254), pH meter (MettlerToleDoFE20 type), balance (MettlerToleDoAL104), detection board (corning, cat3712), detection board bottom sealing film (perkinelmer, cat6005199)
1.2 Experimental methods
In 384 well plates, H is added per well2DCFDA (2, 7-dichlorodihydrofluorescein acetoacetate) and 5-LOX (5. mu.l each), 5. mu.l of secologenin was added to each well, and an equal amount of NDGA (nordihydroguaiaretic acid) was added to a positive control well. Incubate at room temperature for 20 minutes, add arachidonic acid per well, and incubate at room temperature for 60 minutes. The microplate reader detected the fluorescence signal values (Em385nm, Ex535nm) and the inhibition rate was calculated.
Inhibition rate calculation formula: inhibition [% 1- (sample group-sample blank group)/(negative control group-blank control group) ] × 100%
1.3 Experimental results:
TABLE 1 inhibitory Activity of secologanin on 5-LOX
As shown in Table 1, secologanin has a strong inhibitory activity against 5-LOX.
Example 2 therapeutic Effect of secologlycoside intragastric (oral) administration on asthma Guinea pigs
2.1 Experimental materials:
reagent: the antiasthmatic is prepared by mixing histamine phosphate 10mg, acetylcholine chloride 0.2g, and normal saline to obtain 100ml mixed solution (0.2% acetylcholine chloride and 0.01% histamine phosphate) for topical administration. Zileuton, purchased from Henshengtian Biotech limited, Hubei.
Animal guinea pig, green dragon mountain animal breeding farm.
2.2 Experimental methods:
molding: on the first day, the guinea pigs were challenged with histamine phosphate in combination with acetylcholine chloride via a YLS-8A induced cough asthma apparatus for 4 minutes, the asthma latency(s) for the guinea pig tics was recorded, and the symptoms of the guinea pigs within 4 minutes were combined to determine the asthma rating of the guinea pig (asthma rating: 1-exacerbation of breathing; 2-dyspnea; 3-tics; 4-roll, tumble). If the asthma reaches grade four within 4 minutes in the guinea pig, the challenge is stopped.
Grouping and administration: selecting asthmatic guinea pigs, and dividing into model groups, high, medium and low dose groups of secologanin oxide, and 8 positive drug zileuton groups. On the next day, the guinea pigs in the administration group were gavaged with different doses of secologanin, the positive drug was zileuton, and the model group was gavaged with normal saline in an administration volume of 10 ml/kg. The administration was continued for 2 days and after 1h of the last administration, the guinea pigs were challenged again and the asthma latency and asthma grade were recorded and scored for 4 minutes.
2.3 results of the experiment
TABLE 2 Effect of gastric administration of rambutan oxide on asthmatic guinea pigs: (
n＝8)
P <0.05, P <0.01, compared to model groups.
The results show that the high and medium dose groups with the seco-mogroside can obviously prolong the asthma latent period of the asthma guinea pigs, and have significant difference compared with the model group (P <0.05 and P < 0.01). The oral administration of the secologanin oxide is proved to be capable of effectively relieving the asthma symptom of an asthma guinea pig model.
Example 3 therapeutic Effect of administration of secologanin oxide injection on asthmatic rats
3.1 Experimental materials:
dexamethasone sodium phosphate injection (5mg/m1) (Guangzhou Baiyunshanming pharmaceutical Co., Ltd.); sodium hydroxide (Nanjing chemical); ovalbumin (OVA, Sigma Co., USA)
40 animal cleaning grade SD rats are male, the physique is 260 +/-20) g, and the animal breeding farm is a Qinglongshan animal.
3.2 Experimental methods:
molding: SD rats are randomly divided into a normal control group, an asthma model group, a high, medium and low dose group of secologanin oxide and an auxiliary sultone aerosol group, wherein each group comprises 8 rats. Except for the normal control group, the other three groups were treated by intraperitoneal injection of 1mLOVA solution (OVA1mg + aluminum hydroxide 200mg + physiological saline 1mL suspension) into each rat on the 1 st and 8 th day of molding respectively. On day 15 of the experiment, rats were placed in a closed container of 20cm × 20cm × 5cm size and inhaled with 1% OVA by nebulization for 30min each for 7 consecutive days. Normal control group induced asthma with normal saline instead of OVA.
Grouping and administration: the drug is administered on the 1 st day of the experiment, the administration group is injected with different dosages of the seco-mogroside in the abdominal cavity, the positive control is injected with dexamethasone injection (0.5mg/Kg) in the abdominal cavity, and the normal control group and the asthma model group are administered with normal saline 1 time every other day for 7 times.
Detection indexes are as follows: changes in asthma latency in groups of asthmatic rats after OVA nebulization were observed.
3.3 results of the experiment
TABLE 3 Effect of administration of secologanin oxide injection on asthma incubation in asthmatic rats: (
n＝8)
P <0.05, P <0.01, compared to model groups.
The results show that the intraperitoneal injection of high-medium and high-dose secologanin oxide can obviously prolong the asthma latent period of asthma rats, and has significant difference compared with a model group (P <0.05 and P < 0.01).
Example 4 therapeutic Effect of secologlycopersiside on asthma rats by Aerosol inhalation administration
4.1 Experimental materials:
(1) the reagent, cosulfone aerosol (Gelanin Schk group Co.); sodium hydroxide (Nanjing chemical); ovalbumin (OVA, Sigma Co., USA)
(2) 40 animal cleaning grade SD rats are male, the physique is 260 +/-20) g, and the animal breeding farm is a Qinglongshan animal.
4.2 Experimental methods:
molding: SD rats are randomly divided into a normal control group, an asthma model group, a high, medium and low dose group of secologanin oxide and an auxiliary sultone aerosol group, wherein each group comprises 8 rats. Except for the normal control group, the other three groups are injected subcutaneously at 4 points on the two groins and bilateral chests of rats with 0.2mL of freshly prepared suspension of OVA1mg, aluminum hydroxide 200mg and physiological saline 1mL at the 1 st day and the 8 th day of the model respectively, and simultaneously injected with 0.2mL of intraperitoneal injection. Normal control groups were sensitized with saline instead of OVA. On day 15 of the experiment, rats were placed in a closed container of 20cm × 20cm × 5cm size and challenged with 1% OVA by nebulization for 30min each for 7 consecutive days. Normal control group was challenged with saline instead of OVA.
Grouping and administration: administering before inducing asthma every day, placing in a sealed container, continuously spraying atomized semen Strychni Pulveratum glycoside drug solution at a rate of 0.3ml/min for 30min, spraying aspartame as positive control, and administering normal control and asthma model with normal saline 1 time every other day for 7 times.
Detection indexes are as follows: changes in asthma latency in groups of asthmatic rats after OVA nebulization were observed.
4.3 results of the experiment
TABLE 4 Effect of secologlycopersiside aerosol inhalation administration on asthma incubation in asthmatic rats (S)n＝8)
P <0.05, P <0.01, compared to model groups.
The results show that the inhalation of high dose of secologanin can obviously prolong the latent period of asthma rats, and has significant difference compared with a model group (P < 0.01').
In conclusion, the strychnine oxide is broken, so that the asthma incubation period of an asthma animal model can be remarkably prolonged, the asthma symptoms can be effectively relieved, and the mechanism of the strychnine oxide is probably related to the inhibition of the activity of 5-lipoxygenase.
The above embodiments are only exemplary embodiments of the present invention, and are not intended to limit the present invention, and the scope of the present invention is defined by the claims. Various modifications and equivalents may be made by those skilled in the art within the spirit and scope of the present invention, and such modifications and equivalents should also be considered as falling within the scope of the present invention.
Claims (5)
1. Application of secologanin oxide in preparing medicine for treating asthma is provided.
2. The use of claim 1, wherein the asthma treatment medicament further comprises an additional therapeutic agent.
3. The use according to claim 1 or 2, wherein the medicament for treating asthma further comprises a pharmaceutically acceptable carrier.
4. The use according to claim 3, wherein the asthma treatment medicament is an oral, inhalant or injectable formulation.
5. The use according to claim 4, wherein the oral formulation is a powder, tablet, granule, capsule, solution, emulsion or suspension.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2016100168567 | 2016-01-11 | ||
| CN201610016856 | 2016-01-11 |
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| Publication Number | Publication Date |
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| CN105640975A CN105640975A (en) | 2016-06-08 |
| CN105640975B true CN105640975B (en) | 2020-02-28 |
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| KR102157795B1 (en) * | 2018-12-06 | 2020-09-18 | (주)녹십자웰빙 | A pharmaceutical composition comprising water extract of Lonicerae Flos for preventing or treating of Helicobacter pylori infectious diseases |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN100366264C (en) * | 2003-07-03 | 2008-02-06 | 和记黄埔医药企业有限公司 | Cornel extract and use thereof |
| CN100575358C (en) * | 2006-06-07 | 2009-12-30 | 石家庄汉康生化药品有限公司 | Flos Lonicerae extract, its preparation method and application |
| CN105687222A (en) * | 2014-06-06 | 2016-06-22 | 烟台市华文欣欣医药科技有限公司 | Application of pharmaceutical composition in preparing drugs for treating bronchial asthma |
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Non-Patent Citations (2)
| Title |
|---|
| The Screening Research of Anti-Inflammatory Bioactive Markers from Different Flowering Phases of Flos Lonicerae Japonicae;Min Jiang等;《PLOS ONE》;20140531;第9卷(第5期);e96214 * |
| 核因子κB与支气管哮喘发病关系及其临床意义;顾丹等;《中华哮喘杂志（电子版）》;20090630;第3卷(第3期);216-219 * |
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