CN112870212B - Application of Anoectochilus roxburghii glycoside in preparation of medicine for preventing and/or treating pulmonary fibrosis - Google Patents
Application of Anoectochilus roxburghii glycoside in preparation of medicine for preventing and/or treating pulmonary fibrosis Download PDFInfo
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- CN112870212B CN112870212B CN202110197590.1A CN202110197590A CN112870212B CN 112870212 B CN112870212 B CN 112870212B CN 202110197590 A CN202110197590 A CN 202110197590A CN 112870212 B CN112870212 B CN 112870212B
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- 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 provides application of anoectochilus formosanus glycoside in preparation of a medicine for preventing and/or treating pulmonary fibrosis. Creative exploration discovers that the anoectochilus formosanus glycoside and the derivatives thereof have good treatment effect on pulmonary fibrosis, have no adverse reaction and can slow down the pulmonary fibrosis of animals induced by bleomycin hydrochloride. The invention provides a new choice for the medicine for treating pulmonary fibrosis, and simultaneously provides a natural novel medicine source for treating pulmonary fibrosis diseases, and the medicine is efficient, safe and free from toxic and side effects.
Description
Technical Field
The invention belongs to the technical field of medicines. More particularly, relates to application of the anoectochilus formosanus glycoside in preparation of a medicine for preventing and/or treating pulmonary fibrosis.
Background
Fibrosis can occur in a variety of organs, with major pathological changes being fibrous connective tissue augmentation, parenchymal cell reduction, and continued progression leading to destruction of organ structure and function, or even failure, severely threatening human health and life. Any cause can cause the tissue cells to be damaged, and can cause the tissue cells to generate degeneration, necrosis and inflammatory reaction, if the damage is small, the normal parenchymal cells around the damaged cells can generate hyperplasia repair, and the repair can completely restore the normal structure and function. However, if the damage is large or the repeated damage exceeds the regeneration capacity of the parenchymal cells around the damage, the interstitial fibrous connective tissue (extracellular matrix) is proliferated to repair the defective tissue, i.e., the pathological change of fibrosis (fibrosis) occurs. The factors, pathological process development, medication scheme and mechanism of fibrosis of different organs are substantially different, so that no universal and deterministic medication scheme aiming at fibrosis exists clinically.
For example, liver fibrosis (fibrosis of liver) is the abnormal proliferation of connective tissue in liver caused by various pathogenic factors, which is characterized by the excessive abnormal deposition of extracellular interstitial component in liver and affecting the function of liver, and is the stage of chronic liver disease progressing to liver cirrhosis, and liver fibrosis is the precursor lesion of liver cirrhosis, thus having important clinical significance. When lung fibrosis (pulmonary fibrosis) is caused by lung injury due to various reasons, the interstitium can secrete collagen for repair, and if the lung fibrosis is formed by over-repair, namely excessive proliferation of fibroblasts and massive accumulation of extracellular matrix, structural abnormality (scar formation) can be caused after normal alveolar tissues are damaged and abnormal repair is carried out. In addition, pulmonary fibrosis is also frequently developed in diseases related to respiratory virus infection, for example, severe pulmonary fibrosis caused by infection of a novel coronavirus SARS-CoV-2 can lead to severe pulmonary fibrosis, and therefore, the development of drugs for pulmonary fibrosis is imminent.
The natural product is the most common source of the medicine, more and more natural active compounds are discovered along with the continuous increase of research on the natural product in recent years, and compared with western medicines, the natural product has the advantages of rich medicine source, low price, small side effect, multi-link integral treatment and the like, and lays a certain foundation for the research and development of new medicines. For example, patent CN111514158A discloses the application of timosaponin N in the preparation of drugs for preventing and treating pulmonary fibrosis, patent CN111084773A discloses the application of deoxyelephantolide or isodeoxyelephantolide in the preparation of drugs for preventing and treating pulmonary fibrosis, and the like. In addition, the Chinese patent with the publication number of CN109381472A provides the application of the Anoectochilus formosanus glycoside in treating hepatic fibrosis. However, there is no obvious compatibility between different kinds of organ fibrosis based on the differences in the causes, medication schemes and mechanisms of fibrosis. Therefore, the continuous development of more drugs for specific organ fibrosis is of great clinical significance.
Disclosure of Invention
The invention aims to research and develop natural novel drugs for preventing and/or treating pulmonary fibrosis by taking the traditional Chinese medicine theory and the modern pharmacology and pharmacodynamics as guidance. The invention provides application of anoectochilus formosanus glycoside in preparation of a medicine for preventing and/or treating pulmonary fibrosis, and provides a natural novel medicine source which is efficient, safe, free of toxic and side effects and natural for treating pulmonary fibrosis.
The invention aims to provide application of anoectochilus formosanus glycoside and derivatives thereof in preparation of drugs for preventing and/or treating pulmonary fibrosis.
The invention also aims to provide application of the anoectochilus formosanus glycoside and the derivatives thereof in preparing medicaments for preventing and/or treating idiopathic pulmonary fibrosis.
The invention also aims to provide application of the anoectochilus formosanus glycoside and the derivatives thereof in preparing health care products or foods for preventing pulmonary fibrosis.
Another object of the present invention is to provide a medicament for preventing and/or treating pulmonary fibrosis.
Another object of the present invention is to provide an oral liquid for preventing and/or treating pulmonary fibrosis.
Another object of the present invention is to provide a tablet for preventing and/or treating pulmonary fibrosis.
Another object of the present invention is to provide a capsule for preventing and/or treating pulmonary fibrosis.
Another object of the present invention is to provide an aerosol for preventing and/or treating pulmonary fibrosis.
In order to achieve the purpose, the invention is realized by the following technical scheme:
the invention firstly requests to protect the application of the anoectochilus formosanus glycoside and the derivatives thereof in the preparation of the drugs for preventing and/or treating pulmonary fibrosis.
According to the invention, anti-pulmonary fibrosis experiments show that the survival rate of lung fibroblasts can be remarkably reduced in vitro by the Anoectochilus roxburghii glycoside; a pulmonary fibrosis rat model is established through bleomycin hydrochloride, and the result shows that the progress of pulmonary fibrosis is inhibited by increasing SOD activity in lung tissues in the process that the anoectochilus formosanus glycoside is excessively proliferated and secretes a large amount of collagen. And the application of the Anoectochilus roxburghii glycoside in acute and long-term toxicity tests of mice proves that the Anoectochilus roxburghii glycoside has no obvious influence on the increase of body mass of mice, blood routine and blood biochemical indexes and organ coefficients and has no toxic or side effect.
In addition, the application of the anoectochilus formosanus glycoside and the derivatives thereof in the preparation of the medicine for preventing and/or treating idiopathic pulmonary fibrosis is also within the protection scope of the invention.
The application of the anoectochilus formosanus glycoside and the derivatives thereof claimed by the invention in preparing the medicine for preventing and/or treating idiopathic pulmonary fibrosis includes but not limited to, the application of administering an effective amount of the anoectochilus formosanus glycoside and the derivatives thereof disclosed by the invention to a patient to prepare a medicine for preventing or treating diseases caused by pulmonary fibrosis, relieving symptoms of the diseases caused by pulmonary fibrosis, or delaying development or onset of the diseases caused by pulmonary fibrosis.
The anoectochilus formosanus glycoside and the derivatives thereof provided by the invention have no toxic or side effect on organisms, and can be used for preparing health products and foods and preventing pulmonary fibrosis of specific people after daily administration. Therefore, the invention also claims the application of the anoectochilus formosanus glycoside and the derivatives thereof in preparing health care products or foods for preventing pulmonary fibrosis.
The anoectochilus formosanus glycoside and the derivatives thereof claimed by the invention are suitable for daily administration of specific people when preparing health care products or foods for preventing pulmonary fibrosis, have the functions of regulating organism and preventing pulmonary fibrosis, and do not produce any acute, subacute or chronic harm to human bodies.
The anoectochilus formosanus glycosides and derivatives thereof claimed in the present invention are useful for veterinary treatment of pets, animals of the introduced species and animals in farms including mammals, rodents and the like, in addition to human treatment. Other examples of animals include horses, dogs, cats, and the like.
Preferably, the derivative of the anoectochilus formosanus glycoside comprises a molecule, an analogue or a pharmaceutically acceptable salt thereof with the anoectochilus formosanus glycoside as a parent nucleus.
The invention also provides a medicine containing the anoectochilus formosanus glycoside for preventing and/or treating pulmonary fibrosis.
Preferably, the medicament also comprises pharmaceutically acceptable salts, esters, hydrates or combinations thereof of the anoectochilus formosanus glycoside and auxiliary materials.
Preferably, the medicine is prepared into different formulations by adding pharmaceutically acceptable auxiliary materials into the anoectochilus formosanus glycoside, wherein the different formulations comprise powder, tablets, granules, capsules, solutions, syrups, suspensions, injections, powder injections, water injections, aerosols, ointments, eye drops or suppositories.
Preferably, the drug is administered by gastrointestinal administration, injection, respiratory administration, dermal administration, mucosal administration or luminal administration.
In addition, the invention provides an oral liquid for preventing and/or treating pulmonary fibrosis, which comprises the following components in parts by weight: 5-56 parts of anoectochilus roxburghii glycoside, 5-25 parts of antioxidant, 2-21 parts of sweetening agent, 2-18 parts of bacteriostatic agent and 20-200 parts of purified water.
The oral liquid for preventing and/or treating pulmonary fibrosis, provided by the invention, has reasonable compatibility of all components, wherein the anoectochilus formosanus glycoside (kinsenoside) is a special component of the anoectochilus formosanus, is a glycoside formed by connecting glucose and chiral carbon of a five-membered lactone ring in an oxygen-glycoside bond form, and has wide pharmacological activities of improving and inhibiting fibrosis, diminishing inflammation and the like; the antioxidant can prevent the oxidation of the original medicine, so that the stability of the antioxidant is good; the sweetener can improve the taste feeling of a user, so that the adaptability of the sweetener is good; the bacteriostatic agent can effectively prevent the oral liquid from deteriorating; purified water acts as a solvent for dissolution. The obtained oral liquid has obvious effect of resisting pulmonary fibrosis, is beneficial to treatment and rehabilitation of patients, and improves the life quality.
Preferably, the oral liquid comprises the following components in parts by weight: 30-56 parts of anoectochilus roxburghii glycoside, 12-20 parts of antioxidant, 10-18 parts of sweetener, 8-11 parts of bacteriostatic agent and 120-150 parts of purified water.
Preferably, the antioxidant is any one of sodium metabisulfite, vitamin C and sodium sulfite.
Preferably, the sweetener is any one of glucose, fructose, sucrose.
Preferably, the bacteriostatic agent is any one of clove, rosemary and sage.
As a preferred embodiment, the preparation of the oral liquid comprises the steps of:
s1, weighing the following components in parts by weight: 5-56 parts of anoectochilus roxburghii glycoside, 5-25 parts of antioxidant, 2-21 parts of sweetening agent, 2-18 parts of bacteriostatic agent and 20-200 parts of purified water.
S2, adding the anoectochilus formosanus glycoside, the antioxidant, the sweetening agent and the bacteriostatic agent into purified water until the anoectochilus formosanus glycoside, the antioxidant, the sweetening agent and the bacteriostatic agent are completely dissolved, and subpackaging to obtain the finished product.
The invention also provides a tablet for preventing and/or treating pulmonary fibrosis, which comprises the following components in parts by weight: 5-56 parts of anoectochilus formosanus glycoside, 8-26 parts of filling agent, 4-23 parts of adhesive and 2-21 parts of lubricant.
The tablets for preventing and/or treating pulmonary fibrosis provided by the invention have reasonable compatibility of components, wherein the anoectochilus formosanus glycoside (kinsenoside) is a special component of the anoectochilus formosanus and is a glycoside formed by connecting glucose and chiral carbon of a five-membered lactone ring in an oxygen-glycoside bond form, and the anoectochilus formosanus glycoside has pharmacological activities such as inflammation diminishing and the like; the filler can solubilize and increase weight, reduce the cost of the material and play a role in improving the performance of the material; the adhesive is capable of joining two separate materials together by virtue of its adhesive properties, such that it effectively adjusts viscosity; the lubricant can reduce the friction resistance of the friction pair and slow down the abrasion of the friction pair, so that the anti-fibrosis tablet has good lubrication performance, has obvious anti-pulmonary fibrosis effect, is beneficial to the treatment and the rehabilitation of patients, inhibits the loss of organ functions, and protects the health and the life of the people.
Preferably, the tablet comprises the following components in parts by weight: 21-52 parts of roxburgh anoectochilus terminal bud glycoside, 12-26 parts of a filling agent, 12-22 parts of a bonding agent and 8-15 parts of a lubricating agent.
Preferably, the filler is any one of starch, dextrin, and powdered sugar.
Preferably, the binder is any one of methyl cellulose, starch slurry, and hydroxypropyl cellulose.
Preferably, the lubricant is any one of hydrogenated vegetable oil, talcum powder and superfine silica gel powder.
As a preferred possible embodiment, the preparation of the tablet comprises the following steps:
s1, uniformly mixing the anoectochilus formosanus glycoside and the filling agent.
S2, adding an adhesive to prepare a soft material (the soft material can be agglomerated when being held by hands and can be scattered but not be powdery when being lightly pressed by fingers), and extruding and sieving the soft material by hands to obtain particles without strips, blocks or fine powder. In mass production, the soft material is passed through the mesh of the sieve by squeezing with a granulator roller (or a rubbing plate) to obtain granules.
S3, drying at 80 ℃ by adopting a wet particle drying method (drying in an electric heating oven and the like in small-scale preparation and drying in a steam drying room and the like in large-scale production). The dried granules are often agglomerated and adhered, and the granules are sieved and granulated, finally added with a lubricant and uniformly mixed to be tabletted. And (4) obtaining the product.
The invention also provides a capsule for preventing and/or treating pulmonary fibrosis, which comprises the following components in parts by weight: 5-56 parts of roxburgh anoectochilus terminal bud glycoside, 3-40 parts of gelatin, 2-20 parts of plasticizer, 2-12 parts of colorant, 4-40 parts of preservative, 2-12 parts of opacifier, 3-36 parts of diluent, 3-36 parts of lubricant, 2-12 parts of glidant, 3-25 parts of disintegrant and 2-20 parts of wetting agent.
The capsule for preventing and/or treating pulmonary fibrosis provided by the invention has reasonable compatibility of all components, wherein the Anoectochilus roxburghii glycoside (kinsenoside) is a special component of Anoectochilus roxburghii and is glycoside formed by connecting glucose and chiral carbon of a five-membered lactone ring in an oxygen-glycoside bond mode, and the Anoectochilus roxburghii glycoside has wide pharmacological activities of improving and inhibiting fibrosis, diminishing inflammation and the like; gelatin is used as a capsule wall material due to biodegradability, good biocompatibility and film forming property; the plasticizer increases the plasticity of the material; the colorant imparts and improves color; the preservative inhibits the activity of microorganisms and prevents putrefaction and deterioration; the sunscreen agent can absorb ultraviolet rays and prevent ultraviolet rays from penetrating the capsule; the diluent has the functions of improving the physical properties of the contents and increasing the volume; the lubricant has the function of preventing the adhesion of powder and metal materials; the flow aid improves the fluidity of the contents; the disintegrant ensures the disintegration of the content; the wetting agent increases the wettability of the contents with the dissolution medium. The obtained anti-fibrosis capsule has obvious anti-pulmonary fibrosis effect, is beneficial to treatment and rehabilitation of patients, inhibits loss of organ functions, and protects health and life of people.
Preferably, the capsule comprises the following components in parts by weight: 21-44 parts of roxburgh anoectochilus terminal bud glycoside, 22-40 parts of gelatin, 10-14 parts of plasticizer, 4-14 parts of colorant, 8-16 parts of preservative, 8 parts of opacifier, 8-14 parts of diluent, 8-15 parts of lubricant, 8-16 parts of glidant, 8-14 parts of disintegrant and 9-12 parts of wetting agent.
Preferably, the plasticizer is any one of diethyl phthalate, dimethyl phthalate and dibutyl phthalate.
Preferably, the colorant is any one of beet red, amaranth, and cranberry red.
Preferably, the preservative is any one of benzoic acid, sorbic acid and methyl paraben.
Preferably, the opacifier is titanium dioxide.
Preferably, the diluent is any one of mannitol, microcrystalline cellulose, pregelatinized starch.
Preferably, the lubricant is any one of magnesium stearate, talc and stearic acid.
Preferably, the glidant is micropowder silica gel or talcum powder.
Preferably, the disintegrating agent is any one of corn starch, sodium alginate and cross-linked cellulose.
Preferably, the wetting agent is any one of polysorbate, sodium dodecyl sulfate and polysorbate 80.
As a preferred possible embodiment, the preparation of the capsules comprises the following steps:
s1, preparing empty capsules: weighing 3-40 parts of gelatin, 2-20 parts of plasticizer, 2-12 parts of colorant, 4-40 parts of preservative and 2-12 parts of opacifier according to parts by weight, and preparing the empty capsule by six steps of sol, glue dipping, drying, shell pulling, cutting and finishing.
S2, mixing and filling anoectochilus formosanus glycoside and auxiliary materials: weighing 5-56 parts of anoectochilus formosanus glycoside, 3-36 parts of diluent, 3-36 parts of lubricant, 2-12 parts of flow aid, 3-25 parts of disintegrating agent and 2-20 parts of wetting agent according to parts by weight, fully mixing the raw materials, and filling the mixture into empty capsules to obtain the finished product.
The invention also provides an aerosol for preventing and/or treating pulmonary fibrosis, which comprises the following components in parts by weight: 5-56 parts of anoectochilus roxburghii glycoside, 2-40 parts of propellant, 3-35 parts of antioxidant, 3-35 parts of preservative and 20-200 parts of purified water.
The aerosol for preventing and/or treating pulmonary fibrosis, provided by the invention, has reasonable compatibility of all components, wherein the Anoectochilus roxburghii glycoside (kinsenoside) is a special component of Anoectochilus roxburghii and is glycoside formed by connecting glucose and chiral carbon of a five-membered lactone ring in an oxygen-glycoside bond mode, and the Anoectochilus roxburghii glycoside has wide pharmacological activities of improving and inhibiting fibrosis, diminishing inflammation and the like; the propellant is the spraying power source of the aerosol and can be used as a solvent or a diluent of the content; the antioxidant can prevent the oxidation of the original medicine, so that the stability of the antioxidant is good; the antiseptic can inhibit microbial activity and prevent putrefaction. The obtained anti-fibrosis aerosol has obvious anti-fibrosis effect, is beneficial to treatment and rehabilitation of patients, inhibits loss of organ functions, and protects health and life of people.
Preferably, the aerosol comprises the following components in parts by weight: 22-41 parts of anoectochilus roxburghii glycoside, 20-32 parts of propellant, 10 parts of antioxidant, 18-22 parts of preservative and 120-140 parts of purified water.
Preferably, the propellant is trichlorofluoromethane, dichlorodifluoromethane, trichlorotetrafluoroethane.
Preferably, the antioxidant is sodium sulfite, sodium metabisulfite and vitamin C.
Preferably, the preservative is sodium benzoate or sorbic acid.
As a preferred possible embodiment, the preparation of the aerosol comprises the following steps:
s1, glass bottle slush molding: firstly, cleaning and drying a glass bottle, preheating to 120-130 ℃, immersing the glass bottle into plastic slurry while the glass bottle is hot, adhering a layer of plastic slurry below a bottle neck, inverting, and drying for 15 minutes at 150-170 ℃ for later use.
S2, processing and assembling of a valve system: the following treatments were performed on the various parts of the valve: soaking plastic, nylon and rubber products in ethanol, and drying for later use; the stainless steel spring is boiled in 1-3% alkali liquor for half an hour, washed with distilled water for six to seven times until no grease exists, soaked in ethanol and dried for later use. And assembling the processed parts according to the structure of the valve.
And S3, preparing and subpackaging the medicines. Firstly, uniformly mixing 5-56 parts by weight of anoectochilus formosanus glycoside, 2-40 parts by weight of propellant, 3-35 parts by weight of antioxidant, 3-35 parts by weight of preservative and 20-200 parts by weight of purified water.
S4, a pressure irrigation method. And (4) filling the liquid prepared in the step S3 into a glass bottle at room temperature, then installing and tightly rolling a valve, and then pressing the propellant into the glass bottle through a press-fitting machine (preferably, air in the glass bottle is firstly pumped), wherein the operation pressure is preferably 68.65-105.975 kPa. And (5) obtaining the product.
The molecular formula of the anoectochilus formosanus glycoside is C 10 H 16 O 8 Molecular weight 264.23, can be isolated from plants by various methods known in the art, or can be obtained directly from commercial sources.
Compared with the prior art, the invention has the following beneficial effects:
the invention discovers that the natural product Anoectochilus roxburghii glycoside shows better effect of resisting pulmonary fibrosis for the first time, provides a natural novel drug source namely Anoectochilus roxburghii glycoside for treating pulmonary fibrosis, and has the advantages of high efficiency, safety and no toxic or side effect.
Detailed Description
The present invention is further illustrated by the following specific examples, which are not intended to limit the invention in any way. Reagents, methods and apparatus used in the present invention are conventional in the art unless otherwise indicated.
Example 1 inhibitory Effect of Anoectochilus formosanus glycoside on proliferation of Lung fibroblast
1. Experimental methods
Lung fibroblasts were purchased from fenghui bio cells.
(1) Cell culture
Culturing lung fibroblast in high-glucose DMEM medium containing 10% fetal calf serum, 1% penicillin and streptomycin double antibody and glucose concentration of 4.5g/L, and placing the cell at 37 deg.C and containing 5% CO 2 Incubator, 2d change once cell culture fluid. When the cell density is 80-90%, the cells are digested by pancreatin and resuspended for passage.
(2) Administration of drugs
After observing that the cells had good growth status, the cells were digested, resuspended, and fibroblasts were seeded on a black 96-well plate at a density of 3000 cells per well. 24h after cell inoculation, 10ng/mL TGF-beta is added into each hole 1 Establishing a cell pulmonary fibrosis model, and continuously culturing for 24 h.
Administration group: after the cells were attached to the wall, low (12.5. mu.g/mL) and medium (25. mu.g/mL) and high (50. mu.g/mL) concentrations of respectively kinsenoside were administered. After each group was dosed, the 96-well plate was placed in a cell incubator in the dark and cultured for 24 h.
Control group: compared with the administration group, the difference is that no anoectochilin administration is performed.
Blank control group: compared with the administration group, the difference is that TGF-beta is not added 1 Nor was the administration of ectochilin performed.
To avoid systematic errors. Each set was designed with 6 replicate wells, and each set of experiments was replicated 3 times.
(3) CCK8 detection
Cell proliferation rate was measured using CCK 8. According to the kit specification operation, 10 microliter of CCK8 reagent with the concentration of 10% is added into each hole, and the OD value of the cells is detected by adopting a 450nm wavelength of an enzyme-labeling instrument after 2 hours, 12 hours and 24 hours respectively.
(4) Cell survival rate
Cell viability was calculated as OD values of cells detected in each group.
The cell survival rate (administration group OD value-blank control group OD value)/(control group OD value-blank control group OD value) × 100%
2. Results of the experiment
TABLE 1 survival rate of abnormally proliferating lung fibroblasts (%)
| Group of | 2h | 12h | 24h |
| Low concentration (12.5. mu.g/mL) | 62±1.0 | 59±1.4 | 55±2.1 |
| Middle concentration (25. mu.g/mL) | 48±3.1 | 45±3.4 | 39±1.9 |
| High concentration (50. mu.g/mL) | 32±1.7 | 26±3.0 | 20±2.4 |
As can be seen from Table 1, the acteoside has a significant inhibitory effect on the abnormal proliferation of lung fibroblasts, and the inhibitory effect is enhanced with an increase in the dosage.
Example 2 Anoectochilus roxburghii glycoside anti-pulmonary fibrosis experiment
1. Experimental methods
(1) SPF grade Wistar rats, randomly divided by body weight into 5 groups of 30 rats each. The sham operation group, the model group, the high dose (480 mg/(kg. d)), the medium dose (240 mg/(kg. d)), and the low dose group (120 mg/(kg. d)) were respectively included.
(2) Preparation of the model
The experimental animals are bred regularly after being purchased and are adaptive to the environment for 7 d. In the experiment, 3mL/kg of chloral hydrate of 10% is injected into the abdominal cavity to anaesthetize the animal, so that the animal is fixed on a rat board in a supine position, and the neck is sheared. Disinfecting the skin by a conventional method, and making a neck incision with the length of about 0.5-1 cm under aseptic operation. And stripping the exposed trachea layer by layer, and then lifting the head end of the rat board to form an angle of 30-35 degrees with the experiment table board. The method comprises the steps of penetrating a trachea with a 1mL syringe under direct vision, enabling the syringe to be as close to the bifurcation of the trachea as possible, keeping the direction of a needle head consistent with the direction of an airway, quickly injecting and injecting bleomycin hydrochloride (BLOCIN) and 0.2mL of physiological saline solution (15 mg of each bleOCIN, the concentration of the prepared physiological saline solution is 5mg/mL before use, and administering according to the weight of 5 mg/kg), immediately pulling out the needle head, erecting a rat plate, keeping the rat in an upright position, and rotating the rat plate back and forth for 3min to enable liquid medicine to reach the lungs on two sides as far as possible and to be uniformly distributed. Suturing skin, continuously injecting penicillin solution into abdominal cavity for 3 days to prevent wound infection, and placing into cage for conventional breeding after animal naturally revives. The operation method of the rat in the sham operation group is the same as that of other groups, except that the same amount of physiological saline is injected into the trachea after the operation to replace the bleomycin hydrochloride.
(3) Administration of drugs
Each group of rats was administered 1 intragastrically daily from day 2 after intratracheal injection of bleomycin hydrochloride for modeling. The high, medium and low groups of the anoectochilus formosanus glycosides are administered with the anoectochilus formosanus glycosides for 28 days continuously.
(4) Specimen collection and detection
Randomly selecting 10 animals in each group, administrating for 1h on 7 th day, 14 th day and 28 th day after molding, killing, dissecting right lung tissue, adding 9mL physiological saline per gram of lung tissue, making into 10% tissue homogenate, centrifuging at 3000r/min for 10min, collecting supernatant, and detecting lung tissue SOD activity by spectrophotometry.
2. Results of the experiment
TABLE 2 pulmonary tissue SOD Activity in animal models of pulmonary fibrosis
As can be seen from Table 2, the SOD activity in the lung tissues of three batches of animals in the model group after molding is obviously lower than that in the sham operation group, and the SOD activity is reduced along with the extension of the molding time; the results show that the function of the anti-free radical protection system in the lung tissue of the model animal is reduced, and the formation of pulmonary fibrosis is indirectly promoted. Compared with the model group, the lung tissue SOD activity of the anoectochilus formosanus glycoside administration group is obviously improved, which shows that the pulmonary fibrosis process can be inhibited by increasing the SOD activity in the lung tissue in the process of excessive proliferation and secretion of a large amount of collagen of fibroblasts.
Example 3 Anoectochilus formosanus glycoside acute toxicity test
1. Experimental methods
The test was carried out by the maximum tolerance to acute toxicity method. Setting a blank group and a roxburgh anoectochilus terminal bud glycoside (1.4g/mL) group, wherein 2 groups are selected, 30 quarantine-qualified SPF-grade ICR mice are selected, male and female are respectively half, the mice are divided into groups according to sex weights by adopting a random section method, 15 mice in each group are fasted for more than 12 hours before administration, the blank group is not administered, and the drug group is 0.5mL/10g in test Body weight Performing disposable intragastric administration. On the day of administration, particularly, the poisoning performance and characteristics, the occurrence and recovery time of toxic reaction, the death condition and the like of each group of animals are closely observed and recorded within 0-4 h after administration. The observation was then carried out 2 times a day, i.e., 1 time each in the morning and afternoon, for 14 consecutive days. The body mass of the mice was weighed before and on the 7 th and 14 th days after the administration, respectively, using an electronic balance. All mice were anesthetized and sacrificed by pentobarbital sodium intraperitoneal injection after the experiment was finished, and the general dissection was performed, the position, size, color, adhesion and other conditions of the organs were visually observed, and abnormal changes of the texture, effusion, tumor and the like of the surfaces and sections of the organs were examined. Gross dissection should be performed during the trial if there are animals that are not scheduled to die (including moribund animals).
2. Results of the experiment
(1) General activity status of mice
Before the administration and during the 14-day observation period, the mice in the blank group and the administration group had no abnormal or dead behavior as usual.
(2) Toxic symptoms and death in mice
No abnormality and death of the mice were observed during the whole experimental period.
(3) Changes in physical constitution
The mice in the anoectochilus formosanus glycoside group are weighed before administration, 7 th day after administration and 14 th day respectively, and compared with the blank group, the results show that the weight change of the mice in the anoectochilus formosanus glycoside group has no significant difference, and the physical mass growth is within a normal range, which shows that the physical mass growth of the ICR mice is not obviously influenced by orally drenching the anoectochilus formosanus glycoside, and the results are shown in Table 3.
TABLE 3 Effect of Anoectochilus formosanus glycosides on mouse body weight
(4) Gross anatomical examination results
No obvious abnormal condition is found on the surface and section of each organ of each group of mice.
Example 4 Long-term toxicity test of Anoectochilus formosanus glycoside
1. Experimental methods
80 mice were randomly divided into 4 groups of 20 mice, namely a control group, a high-dose group (600mg/kg), a medium-dose group (480mg/kg) and a low-dose group (240 mg/kg). The administration was 1 time per day, and 10 mice were sacrificed separately for index detection in each fraction after 3 months of administration and 2 weeks of withdrawal (recovery period). The following experiment was performed thereafter.
Mice were observed daily for normality of skin surface, mucous membranes, secretions and excretions, while general manifestations, toxic manifestations and mortality were recorded. Mice were recorded every 7d for water intake, feed intake and body weight. Collecting blood and performing a dissection test on a certain number of mice on both day 30 and day 45, and detecting hematology and blood biochemical indexes, wherein the hematology indexes comprise: differential counting of White Blood Cells (WBC) and Neutrophils (NE), Eosinophils (EO), Basophils (BA), Lymphocytes (LY), Monocytes (MO), Red Blood Cells (RBC) and Hemoglobin (HB), etc.; the biochemical indexes of the blood comprise: alanine aminotransferase (alanine aminotransferase, ALT), aspartate aminotransferase (aspartate aminotransferase, AST), Albumin (ALB), urea nitrogen (BUN), and Triglyceride (TG), and the like. The main organs (heart, liver, spleen, lung, kidney, gastrointestinal and reproductive organs) of each group of mice were weighed and the organ coefficients were calculated, and the control group and the high dose group of mice were subjected to pathological examination.
2. Results of the experiment
(1) Weight change
During the test period, all mice in all groups had good mental status, normal drinking water and appetite, normal defecation and urination, and smooth and clean hair color. The weight growth trend of the test group and the blank group has no significant difference.
(2) Blood routine and blood biochemical detection
After 3 months of administration, the blood routine and blood biochemical detection of the high, medium and low dose groups SD mice of the anoectochilus formosanus glycoside have no obvious difference compared with the control group.
(3) Histopathological changes
The organ coefficients of each group on the 30 th day and the 45 th day have no difference significance. No obvious abnormality is seen on the surfaces of organs such as heart, liver, spleen, lung, kidney, stomach, small intestine, testis and ovary of mice in each group of eye; no obvious lesions were observed in each tissue section of the test and blank groups.
Example 5 oral liquid 1 for prevention and/or treatment of pulmonary fibrosis
1. This example provides an oral liquid, which comprises, by weight, 30 parts of anoectochilus formosanus glycoside, 12 parts of sodium metabisulfite, 10 parts of glucose, 8 parts of clove, and 120 parts of purified water.
2. Preparation method
S1, weighing the following components in parts by weight: 30 parts of anoectochilus formosanus glycoside, 12 parts of sodium metabisulfite, 10 parts of glucose, 8 parts of clove and 120 parts of purified water.
S2, adding the anoectochilus formosanus glycoside, sodium metabisulfite, glucose and clove into purified water until the anoectochilus formosanus glycoside, the sodium metabisulfite, the glucose and the clove are completely dissolved, and subpackaging to obtain the finished product.
Example 6 oral liquid 2 for prevention and/or treatment of pulmonary fibrosis
1. The embodiment provides an oral liquid which comprises, by weight, 56 parts of anoectochilus formosanus glycoside, 20 parts of vitamin C, 18 parts of fructose, 11 parts of rosemary and 150 parts of purified water.
2. The preparation method comprises the following steps: adding Anoectochilus roxburghii glycoside, vitamin C, fructose and herba Rosmarini officinalis into purified water until completely dissolved, and packaging.
Example 7 oral liquid 3 for prevention and/or treatment of pulmonary fibrosis
1. This example provides an oral liquid, which comprises, by weight, 40 parts of anoectochilus formosanus glycoside, 15 parts of sodium sulfite, 14 parts of sucrose, 9 parts of salvia officinalis and 130 parts of purified water.
2. The preparation method comprises the following steps: adding Anoectochilus roxburghii glycoside, sodium sulfite, sucrose and herba Salvia officinalis into purified water until completely dissolved, and packaging.
Example 8 tablet 1 for prevention and/or treatment of pulmonary fibrosis
1. This example provides a tablet comprising, by weight, 21 parts of roxburgh anoectochilus terminal bud glycoside, 12 parts of starch slurry, and 8 parts of hydrogenated vegetable oil.
2. Preparation method
S1, uniformly mixing the anoectochilus formosanus glycoside and starch.
S2, adding starch slurry to prepare a soft material (the soft material can be agglomerated when being held by hands and can be scattered but not be powdery when being lightly pressed by fingers), and extruding and sieving by hands to obtain particles without strips, blocks and fine powder. In mass production, the soft material is passed through the mesh of the sieve by squeezing with a granulator roller (or a rubbing plate) to obtain granules.
S3, drying at 80 ℃ by adopting a wet particle drying method (drying in an electric heating oven and the like in small-scale preparation and drying in a steam drying room and the like in large-scale production). The dried granules are often conglobated and adhered, and sieving and grading are needed, and finally hydrogenated vegetable oil is added, and tabletting can be carried out after uniform mixing. And (5) obtaining the product.
Example 9 tablet 2 for the prevention and/or treatment of pulmonary fibrosis
1. This example provides a tablet, which comprises, by weight, 36 parts of roxburgh anoectochilus terminal bud glycoside, 20 parts of dextrin, 20 parts of hydroxypropyl cellulose, and 10 parts of talc powder.
2. Preparation method
S1, mixing the anoectochilus formosanus glycoside and dextrin uniformly.
S2, adding hydroxypropyl cellulose to prepare a soft material (the soft material can be agglomerated when being held by a hand, and can be scattered to be not powdery when being lightly pressed by fingers), and extruding and sieving by the hand to obtain granules without strips, lumps or fine powder. In mass production, the soft material is passed through the mesh of the sieve by squeezing with a granulator roller (or a rubbing plate) to obtain granules.
S3, drying at 80 ℃ by adopting a wet particle drying method (drying in an electric heating oven and the like in small-scale preparation and drying in a steam drying room and the like in large-scale production). The dried granules are often agglomerated and adhered, and sieving and finishing are needed, and finally, the talcum powder is added, and tabletting can be carried out after even mixing. And (5) obtaining the product.
Example 10 tablet 3 for prevention and/or treatment of pulmonary fibrosis
1. This example provides a tablet, which comprises, by weight, 52 parts of Anoectochilus roxburghii glycoside, 26 parts of powdered sugar, 22 parts of methylcellulose and 15 parts of aerosil.
2. Preparation method
S1, mixing the anoectochilus formosanus glycoside and the powdered sugar uniformly.
S2, adding methyl cellulose to prepare a soft material (the soft material can be agglomerated when being held by hands and can be scattered but not be powdery when being lightly pressed by fingers), and extruding and sieving by hands to obtain particles without strips, blocks and fine powder. In mass production, the soft material is passed through the mesh of the sieve by squeezing with a granulator roller (or a rubbing plate) to obtain granules.
S3, drying at 80 ℃ by adopting a wet particle drying method (drying in an electric heating oven and the like in small-scale preparation and drying in a steam drying room and the like in large-scale production). The dried granules tend to agglomerate and adhere, and are sieved and granulated, and finally the superfine silica gel powder is added, and tabletting can be carried out after uniform mixing. And (5) obtaining the product.
EXAMPLE 11 Capsule 1 for the prevention and/or treatment of pulmonary fibrosis
1. The embodiment provides a capsule which comprises, by weight, 21 parts of roxburgh anoectochilus terminal bud glycoside, 22 parts of gelatin, 10 parts of diethyl phthalate, 4 parts of beet red, 8 parts of benzoic acid, 8 parts of titanium dioxide, 8 parts of mannitol, 8 parts of magnesium stearate, 8 parts of aerosil, 8 parts of corn starch and 809 parts of polysorbate.
2. Preparation method
S1, preparing empty capsules. 22 parts of gelatin, 10 parts of diethyl phthalate, 4 parts of beet red, 8 parts of benzoic acid and 8 parts of titanium dioxide are weighed. Dissolving the gelatin, dipping the gelatin, drying, pulling out the shell, cutting and finishing to prepare the empty capsule.
S2, mixing and filling anoectochilus formosanus glycoside and auxiliary materials. 21 parts of anoectochilus formosanus glycoside, 8 parts of mannitol, 8 parts of magnesium stearate, 8 parts of aerosil, 8 parts of corn starch and 809 parts of polysorbate. Mixing above materials, and filling into empty capsule.
EXAMPLE 12 Capsule 2 for the prevention and/or treatment of pulmonary fibrosis
1. The embodiment provides a capsule which comprises, by weight, 32 parts of roxburgh anoectochilus terminal bud glycoside, 34 parts of gelatin, 10 parts of dimethyl phthalate, 10 parts of amaranth, 12 parts of sorbic acid, 8 parts of titanium dioxide, 10 parts of microcrystalline cellulose, 10 parts of talcum powder, 12 parts of superfine silica gel powder, 10 parts of sodium alginate and 12 parts of sodium dodecyl sulfate.
2. Preparation method
S1, preparing empty capsules. 34 parts of gelatin, 10 parts of dimethyl phthalate, 10 parts of amaranth, 12 parts of sorbic acid and 8 parts of titanium dioxide are weighed. The empty capsule is prepared by six steps of sol dissolving, glue dipping, drying, shell pulling, cutting and finishing.
S2, mixing and filling anoectochilus formosanus glycoside and auxiliary materials. 32 parts of anoectochilus formosanus glycoside, 10 parts of microcrystalline cellulose, 10 parts of talcum powder, 12 parts of micro-powder silica gel, 10 parts of sodium alginate and 12 parts of sodium dodecyl sulfate. Mixing above materials, and filling into empty capsule.
EXAMPLE 13 Capsule 3 for the prevention and/or treatment of pulmonary fibrosis
1. The embodiment provides a capsule which comprises, by weight, 44 parts of roxburgh anoectochilus terminal bud glycoside, 40 parts of gelatin, 14 parts of dibutyl phthalate, 14 parts of cranberry red, 16 parts of methyl p-hydroxybenzoate, 8 parts of titanium dioxide, 14 parts of pregelatinized starch, 15 parts of stearic acid, 16 parts of talcum powder, 14 parts of cross-linked cellulose and 8010 parts of polysorbate.
2. Preparation method
S1, preparing empty capsules. Weighing 40 parts of gelatin, 14 parts of dibutyl phthalate, 14 parts of cranberry red, 16 parts of methyl p-hydroxybenzoate and 8 parts of titanium dioxide. The empty capsule is prepared by six steps of sol dissolving, glue dipping, drying, shell pulling, cutting and finishing.
S2, mixing and filling anoectochilus formosanus glycoside and auxiliary materials. 44 parts of anoectochilus formosanus glycoside, 14 parts of pregelatinized starch, 15 parts of stearic acid, 16 parts of talcum powder, 14 parts of cross-linked cellulose and 8010 parts of polysorbate. Mixing above materials, and filling into empty capsule.
EXAMPLE 14 Aerosol 1 for the prevention and/or treatment of pulmonary fibrosis
1. This example provides an aerosol, which comprises 22 parts by weight of Anoectochilus roxburghii glycoside, 20 parts by weight of trichlorofluoromethane, 10 parts by weight of sodium sulfite, 19 parts by weight of sodium benzoate and 120 parts by weight of purified water.
2. Preparation method
S1, glass bottle slush molding: firstly, cleaning and drying a glass bottle, preheating to 120-130 ℃, immersing the glass bottle into plastic slurry while the glass bottle is hot, adhering a layer of plastic slurry below a bottle neck, inverting, and drying for 15 minutes at 150-170 ℃ for later use.
S2, processing and assembling of a valve system: the following treatments were performed on the various parts of the valve: soaking plastic, nylon and rubber products in ethanol, and drying for later use; the stainless steel spring is boiled in 1-3% alkali liquor for half an hour, washed with distilled water for six to seven times until no grease exists, soaked in ethanol and dried for later use. And assembling the processed parts according to the structure of the valve.
And S3, preparing and subpackaging the medicines. Mixing herba Anoectochili Roxburghii glycoside, sodium sulfite, sodium benzoate and purified water.
S4, a pressure irrigation method. And (4) filling the liquid prepared in the step S3 into a glass bottle at room temperature, then installing and tightly rolling a valve, and then pressing trichlorofluoromethane into the glass bottle by a press-fitting machine (preferably, air in the glass bottle is firstly pumped out), wherein the operation pressure is preferably 68.65-105.975 kPa. And (5) obtaining the product.
EXAMPLE 15 Aerosol 2 for the prevention and/or treatment of pulmonary fibrosis
1. This example provides an aerosol comprising, by weight, 32 parts of Anoectochilus roxburghii glycoside, 21 parts of dichlorodifluoromethane, 10 parts of sodium metabisulfite, 18 parts of sorbic acid, and 140 parts of purified water.
2. Preparation method
S1, glass bottle slush molding: firstly, cleaning and drying a glass bottle, preheating to 120-130 ℃, immersing the glass bottle into plastic slurry while the glass bottle is hot, adhering a layer of plastic slurry below a bottle neck, inverting, and drying for 15 minutes at 150-170 ℃ for later use.
S2, processing and assembling of a valve system: the following treatments were performed on the various parts of the valve: soaking plastic, nylon and rubber products in ethanol, and drying for later use; the stainless steel spring is boiled in 1-3% alkali liquor for half an hour, washed with distilled water for six to seven times until no grease exists, soaked in ethanol and dried for later use. And assembling the processed parts according to the structure of the valve.
And S3, preparing and subpackaging the medicines. Mixing herba Anoectochili Roxburghii glycoside, sodium pyrosulfite, sorbic acid and purified water uniformly. .
S4, a pressure irrigation method. And (4) filling the liquid prepared in the step S3 into a glass bottle at room temperature, then installing and tightly rolling a valve, and then pressing dichlorodifluoromethane into the glass bottle through a press-fitting machine (preferably, air in the glass bottle is firstly pumped out), wherein the operation pressure is preferably 68.65-105.975 kPa. And (5) obtaining the product.
EXAMPLE 16 Aerosol 3 for the prevention and/or treatment of pulmonary fibrosis
1. This example provides an aerosol, which comprises, by weight, 41 parts of Anoectochilus roxburghii glycoside, 32 parts of trichlorotetrafluoroethane, 10 parts of vitamin C, 22 parts of sodium benzoate, and 130 parts of purified water.
2. Preparation method
S1, glass bottle slush molding: firstly, cleaning and drying a glass bottle, preheating to 120-130 ℃, immersing the glass bottle into plastic slurry while the glass bottle is hot, adhering a layer of plastic slurry below a bottle neck, inverting, and drying for 15 minutes at 150-170 ℃ for later use.
S2, processing and assembling of a valve system: the following treatments were performed on the various parts of the valve: soaking plastic, nylon and rubber products in ethanol, and drying for later use; the stainless steel spring is boiled in 1-3% alkali liquor for half an hour, washed with distilled water for six to seven times until no grease exists, soaked in ethanol and dried for later use. And assembling the processed parts according to the structure of the valve.
And S3, preparing and subpackaging the medicines. Mixing herba Anoectochili Roxburghii glycoside, vitamin C, sodium benzoate, and purified water.
S4, a pressure irrigation method. And (4) filling the liquid prepared in the step S3 into a glass bottle at room temperature, then installing and tightly rolling a valve, and then pressing trichlorotetrafluoroethane into the glass bottle by a press-fitting machine (preferably, air in the glass bottle is firstly pumped), wherein the operation pressure is preferably 68.65-105.975 kPa. And (5) obtaining the product.
Application of Anoectochilus formosanus glycoside product in pulmonary fibrosis resistance experiment
The oral liquid 1, the tablet 1, the capsule 1 and the aerosol 1 were administered to the rat pulmonary fibrosis model according to the method of example 2.
1. Experimental method
(1) Grouping animals
SPF grade rats were randomly divided into 6 groups of 30 rats by body weight. Respectively a pseudo-operation group, a model group, an oral liquid 1 group, a tablet 1 group, a capsule 1 group and an aerosol 1 group.
(2) Preparation of the model
The experimental animals are bred regularly after being purchased and are adaptive to the environment for 7 d. In the experiment, 3mL/kg of chloral hydrate of 10% is injected into the abdominal cavity to anaesthetize the animal, so that the animal is fixed on a rat board in a supine position, and the neck is sheared. Disinfecting the skin by a conventional method, and making a neck incision with the length of about 0.5-1 cm under aseptic operation. And stripping the exposed trachea layer by layer, and then lifting the head end of the rat board to form an angle of 30-35 degrees with the experiment table board. The method comprises the steps of penetrating a trachea with a 1mL syringe under direct vision, enabling the syringe to be as close to the bifurcation of the trachea as possible, keeping the direction of a needle head consistent with the direction of an airway, quickly injecting and injecting bleomycin hydrochloride (BLOCIN) and 0.2mL of physiological saline solution (15 mg of each bleOCIN, the concentration of the prepared physiological saline solution is 5mg/mL before use, and administering according to the weight of 5 mg/kg), immediately pulling out the needle head, erecting a rat plate, keeping the rat in an upright position, and rotating the rat plate back and forth for 3min to enable liquid medicine to reach the lungs on two sides as far as possible and to be uniformly distributed. Suturing skin, continuously injecting penicillin solution into abdominal cavity for 3 days to prevent wound infection, and placing into cage for conventional breeding after animal naturally revives. The operation method of the rat operation in the sham operation group is the same as that in other groups, except that the same amount of physiological saline is injected into the trachea after the operation to replace the bleomycin hydrochloride.
(3) Administration of drugs
Each group of rats is administrated 1 time per day according to the requirements of dosage forms from 2 days after the model is built by injecting bleomycin hydrochloride into trachea. 480 mg/(kg. d) of oral liquid 1, tablet 1, capsule 1 and aerosol 1 were administered for 28 days.
(4) Collecting and detecting a specimen:
randomly selecting 10 animals in each group, administrating for 1h on 7 th day, 14 th day and 28 th day after molding, killing, dissecting right lung tissue, adding 9mL physiological saline per gram of lung tissue, making into 10% tissue homogenate, centrifuging at 3000r/min for 10min, collecting supernatant, and detecting lung tissue SOD activity by spectrophotometry.
2. Results of the experiment
TABLE 4 pulmonary tissue SOD Activity in animal models of pulmonary fibrosis
The results show that the SOD activity in the lung tissues of three batches of animals in the model group is obviously lower than that in the false operation group after the model is made, and the SOD activity is reduced along with the prolonging of the model making time; the results show that the function of the anti-free radical protection system in the lung tissue of the model animal is reduced, and the formation of pulmonary fibrosis is indirectly promoted. SOD activity in the lung tissues of the animals in the 4 administration groups is obviously improved compared with that in the model group, which shows that the SOD activity in the lung tissues is increased to inhibit the pulmonary fibrosis process in the processes of excessive proliferation of fibroblasts and secretion of a large amount of collagen in the oral liquid 1 group, the tablet 1 group, the capsule 1 group and the aerosol 1 group.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (7)
1. Application of Anoectochilus roxburghii glycoside in preparation of medicine for preventing and/or treating pulmonary fibrosis is provided.
2. Application of Anoectochilus roxburghii glycoside in preparing medicine for preventing and/or treating idiopathic pulmonary fibrosis is disclosed.
3. The use of claim 1 or 2, wherein the medicament is in the form of powder, tablet, granule, capsule, syrup, suspension, powder injection, water injection, aerosol, ointment, eye drop or suppository.
4. The use of claim 1 or 2, wherein the medicament is an oral liquid comprising the following components in parts by weight: 5-56 parts of anoectochilus roxburghii glycoside, 5-25 parts of antioxidant, 2-21 parts of sweetening agent, 2-18 parts of bacteriostatic agent and 20-200 parts of purified water.
5. The use according to claim 1 or 2, wherein the medicament is a tablet comprising the following components in parts by weight: 5-56 parts of anoectochilus formosanus glycoside, 8-26 parts of filling agent, 4-23 parts of adhesive and 2-21 parts of lubricant.
6. The use according to claim 1 or 2, wherein the medicament is a capsule comprising the following components in parts by weight: 5-56 parts of roxburgh anoectochilus terminal bud glycoside, 3-40 parts of gelatin, 2-20 parts of plasticizer, 2-12 parts of colorant, 4-40 parts of preservative, 2-12 parts of opacifier, 3-36 parts of diluent, 3-36 parts of lubricant, 2-12 parts of glidant, 3-25 parts of disintegrant and 2-20 parts of wetting agent.
7. The use according to claim 1 or 2, wherein the medicament is an aerosol comprising the following components in parts by weight: 5-56 parts of anoectochilus roxburghii glycoside, 2-40 parts of propellant, 3-35 parts of antioxidant, 3-35 parts of preservative and 20-200 parts of purified water.
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