A pharmaceutical composition and its use

Abstract

This invention relates to the field of pharmaceutical formulation technology, specifically disclosing a pharmaceutical composition and its uses. The pharmaceutical composition comprises an active ingredient and an emulsifier, wherein the active ingredient consists of eucalyptol, limonene, and α-pinene, and the emulsifier is a composite emulsifier containing at least two types of emulsifiers. The weight ratio of the active ingredient to the emulsifier is 1:(0.8–1.5). The pharmaceutical composition of this invention exhibits self-emulsifying properties, short dispersion time, and droplet size down to the nanometer level, significantly improving bioavailability and shortening the time to peak concentration. It also demonstrates good stability, a simple formulation, and ease of production and quality control. It is suitable for relieving cough, inflammation, expectoration, promoting contrast agent excretion, or treating respiratory diseases such as sinusitis, bronchitis, and pneumonia.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical preparations, and more specifically to a pharmaceutical composition and its use. Background Technology

[0002] Self-emulsifying drug delivery systems (SEDDS) are homogeneous, clear, and isotropic solutions composed of oil solutions and surfactants, and sometimes also include solubilizers. After oral administration, these systems spontaneously form an oil-in-water emulsion in the aqueous phase of gastric juice due to gastric motility and the presence of emulsifiers, which helps increase drug solubility and absorption rate.

[0003] Eucalyptol and limonene oil is a composition comprising eucalyptol, limonene, and α-pinene, and has expectorant properties. All three components are oil-phase substances with a strong odor. Currently, the oil-phase substances of the three components are encapsulated in soft capsules to prepare enteric-coated capsules for use. There is a need in the art to provide an eucalyptol and limonene capsule formulation, which is expected to further improve bioavailability. Summary of the Invention

[0004] The present invention aims to at least partially solve the technical problems in the prior art, and provides a pharmaceutical composition and its use.

[0005] A first aspect of the present invention provides a pharmaceutical composition comprising an active ingredient and an emulsifier, wherein, The active ingredients include eucalyptol, limonene, and α-pinene; The emulsifier is a composite emulsifier, comprising at least two types of emulsifiers; The weight ratio of the active ingredient to the emulsifier is 1:(0.8-1.5).

[0006] A second aspect of the present invention provides a capsule comprising an active ingredient and an emulsifier, wherein the active ingredient comprises eucalyptol, limonene, and α-pinene; and the content of the active ingredient in a unit dose of the capsule is 50-70 mg.

[0007] The third aspect of the present invention provides the use of the pharmaceutical composition or capsules described above in the preparation of a medicament for the purpose of relieving cough, reducing inflammation, expectorating phlegm, promoting the excretion of contrast agents, or treating respiratory diseases.

[0008] A fourth aspect of the present invention provides a method for treating a disease, comprising administering to a patient a single dose of the pharmaceutical composition or capsules described above, in an amount of 30 to 240 mg (e.g., 60 mg, 120 mg, 180 mg, 240 mg) of the active ingredient, wherein the respiratory disease includes at least one of sputum, cough, acute sinusitis, chronic sinusitis, acute bronchitis, chronic bronchitis, pneumonia, lung abscess, chronic obstructive pulmonary disease, pulmonary fungal infection, tuberculosis, silicosis, and pulmonary interstitial fibrosis.

[0009] The fifth aspect of the present invention provides a method for promoting the excretion of contrast agents, comprising administering a single dose to a patient a pharmaceutical composition or capsule as described above, in an amount of 30 to 240 mg (e.g., 60 mg, 120 mg, 180 mg, 240 mg) of the active ingredient.

[0010] The present invention has the following positive and progressive effects: (1) The pharmaceutical composition or capsules prepared in this application have a short dispersion time and droplet size that can reach the nanometer level, which is beneficial to increasing the contact area with the digestive tract mucosa and improving the drug absorption rate. Reducing the amount of emulsifier (0.8 to 1.5 times) does not substantially affect the emulsification effect of the formulation, and reduces the amount of excipients, resulting in smaller particle size of the prepared soft capsules, which is easier to swallow and can further improve patient compliance. In addition, the small amount of excipients can save production costs. Furthermore, the formulation of this application has simple components, is easy to produce and control in terms of quality, and is suitable for industrial production.

[0011] (2) Animal experiments show that this application has better bioavailability and shorter time to peak compared with commercially available drugs. In particular, when Tween 80 is used as the second emulsifier, the relative bioavailability of the three active ingredients is better when the ratio of emulsifier to eucalyptol oil is 0.8 to 1.5. Furthermore, the time to peak is shorter, the safety is better, and it has more advantages in drug development.

[0012] (3) The applicant found through dosage studies that the drug composition or capsules can achieve bioavailability similar to commercially available eucalyptol enteric-coated capsules when the single dose is 120 mg. Therefore, the drug composition or capsules are prepared into 50-70 mg (especially 60 mg) capsules. The capsule size is suitable for swallowing and the dosage can be effectively adjusted according to the number of capsules given. It is more suitable to prepare it into a clinical dosage form.

[0013] (4) Furthermore, the formulation of this application has good stability, can be stored at room temperature for a long time, has stable quality and can maintain good performance, providing a reliable guarantee for clinical application. Detailed Implementation

[0014] In some specific embodiments, the weight ratio of the active ingredient to the emulsifier in the pharmaceutical composition or the capsule is 1:(0.8 to 1.5) (e.g., 1:0.8, 1:0.9, 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5), preferably 1:(0.8 to 1.1), more preferably 1:(0.9 to 1).

[0015] In some specific embodiments, the emulsifier in the pharmaceutical composition or the capsule is a composite emulsifier, which contains at least two components.

[0016] In some specific embodiments, the composite emulsifier in the pharmaceutical composition or the capsule has an HLB value of 13 to 15 (e.g., 13, 13.5, 13.7, 14, 14.2, 14.3, 14.4, 14.5, 14.7, 15).

[0017] In some specific embodiments, the emulsifier in the pharmaceutical composition or the capsule is selected from at least two of polyethylene glycol glycerol caprylate, Tween, polyoxyethylene castor oil, and polyoxyethylene hydrogenated castor oil.

[0018] In some specific embodiments, the emulsifier in the pharmaceutical composition or the capsule comprises a first emulsifier and a second emulsifier; the first emulsifier is selected from polyethylene glycol glycerol ester (PEG-C); and the second emulsifier is selected from one or more of Tween and polyoxyethylene castor oil.

[0019] In some specific embodiments, the Tween described in this application is preferably Tween 80.

[0020] In some specific embodiments, the polyoxyethylene castor oil described in this application is preferably polyoxyethylene (35) castor oil (abbreviated as EL-35).

[0021] Preferably, in the pharmaceutical composition or capsule, the emulsifier is polyethylene glycol glycerol caprylate and Tween (such as Tween 80).

[0022] In some specific embodiments, the weight ratio of the first emulsifier to the second emulsifier is 1:1 to 3.2:1 (e.g., 1.3:1, 1:4:1, 1.5:1, 1.8:1, 1.9:1, 2.3:1, 2.5:1, 3:1 or 3.2:1, etc.), preferably 1.5:1 to 3.2:1, and more preferably 1.8:1 to 2.3:1.

[0023] In some specific embodiments, the pharmaceutical composition or capsule may be further supplemented with an emulsifying agent, such as ethanol, propylene glycol (e.g., 1,2-propanediol), polyethylene glycol, or diethylene glycol monoethyl ether. The content of the emulsifying agent shall not exceed 20% of the total mass of the pharmaceutical composition or capsule, preferably not more than 10%, and more preferably not more than 5%.

[0024] In some specific embodiments, preferably, the pharmaceutical composition or capsules described in this application do not contain additional emulsifiers as described above, but this does not exclude the presence of ethanol, propylene glycol, polyethylene glycol, or transcutol as impurities introduced or not completely removed from other raw materials, excipients, or during the preparation process.

[0025] In some specific embodiments, the pharmaceutical composition or capsule may be further supplemented with oils, such as soybean oil, medium-chain triglycerides, ethyl oleate, corn oil, etc. The content of the oils does not exceed 20% of the total mass of the pharmaceutical composition or capsule, preferably not more than 10%, and more preferably not more than 5%.

[0026] In some specific implementations, the pharmaceutical composition or capsules are preferably not additionally coated with oils (the types of oils are as shown above).

[0027] In some specific embodiments, the weight ratio of eucalyptol, limonene and α-pinene in the pharmaceutical composition or the capsule is (3~5):(2~4):1, preferably (3~4.6):(2~3):1, or (3~4):(2~3):1.

[0028] In some specific embodiments, the active ingredients of this application as described above are composed of eucalyptol, limonene and α-pinene. Those skilled in the art should understand that in this case, it is not excluded that other substances may exist as impurities in the active ingredients if the dosage is permissible.

[0029] In some specific embodiments, the pharmaceutical composition is a self-emulsifying formulation. It is common knowledge in the art that self-emulsifying formulations generally do not contain added water.

[0030] In some specific embodiments, the pharmaceutical composition is prepared into a capsule, which may be a soft capsule or a hard capsule.

[0031] In some specific embodiments, the capsule is a soft capsule formulation or a hard capsule formulation.

[0032] In some specific embodiments, the content of the active ingredient in a unit dose of the pharmaceutical composition is 50-70 mg, preferably 60 mg.

[0033] In some specific embodiments, the content of active ingredient in each self-emulsifying soft capsule formulation is 50-70 mg, preferably 60 mg.

[0034] In some specific embodiments, the respiratory diseases include at least one of the following: acute sinusitis, chronic sinusitis, acute bronchitis, chronic bronchitis, pneumonia, lung abscess, chronic obstructive pulmonary disease, pulmonary fungal infection, pulmonary tuberculosis, silicosis, and pulmonary interstitial fibrosis.

[0035] In some specific embodiments, the method of treating the disease or the method of promoting the removal of contrast agents includes administering a single dose to the patient of the pharmaceutical composition or capsules described above, in a dose of 30 to 240 mg (e.g., 60 mg, 120 mg, 180 mg, 240 mg) of the active ingredient.

[0036] In this invention, the unit dose refers to the dose in the smallest packaging form of the pharmaceutical composition (which can be understood as a pharmaceutical specification), such as the content of the active ingredient in a tablet, pill, sachet, bottle, tube, or packet. A unit dose of capsules refers to the content of the active ingredient in a single tablet, sachet, or other smallest packaging form of capsule.

[0037] The endpoint values ​​or range values ​​of one or more numerical values ​​described in this application should be understood to also include values ​​adjacent to the endpoint value or the defined range value. For example, those skilled in the art will understand that a variation of 10% (preferably 5%, such as 4%, 3%, 2% or 1%) of the upper or lower limit of the range may be applicable and may also be within the scope of protection of this application.

[0038] Additional aspects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention.

[0039] Unless otherwise stated, all embodiments or different preferred schemes described in this application may be combined arbitrarily.

[0040] The present invention will be explained below with reference to embodiments. Those skilled in the art will understand that the following embodiments are for illustrative purposes only and should not be considered as limiting the scope of the invention. Where specific techniques or conditions are not specified in the embodiments, they are performed according to the techniques or conditions described in the literature in the field or according to the product instructions. Reagents or instruments whose manufacturers are not specified are all conventional products that can be obtained commercially.

[0041] Example

[0042] Examples 1-2: Preparation of soft capsules and emulsification effect test The emulsification effect test method is as follows: The emulsification effect of different soft capsule formulations was tested using dispersion time, dispersion phenomenon, and droplet size as indicators.

[0043] The specific procedures are as follows: Take the contents of each soft capsule, add an equal amount of purified water, place them in a rotary mixer, and stir at 100 rpm. Simultaneously measure the dispersion time and observe the dispersion of the contents. The droplet size is measured using a Brookhaven 90PLUS PLAS laser nanoparticle size analyzer via light scattering.

[0044] Example 1: The effect of emulsifier selection on emulsification effect

[0045] The specific component amounts of the soft capsules prepared in this experiment are shown in Table 1, and the preparation method is as follows: 1) Weigh eucalyptol, limonene and α-pinene according to a weight ratio of 3:2:1, stir at 20°C for 1 hour to obtain the eucalyptol-limonene-pinene oil phase; 2) Take the prescribed amount of excipients (emulsifiers are: PEG-C-glycerol Caprylic / Capric Acid, Tween 80, Polyoxyethylene Castor Oil (EL-35) or Polyoxyethylene Hydrogenated Castor Oil; co-emulsifiers are: propylene glycol or diethylene glycol monoethyl ether (Transcutol); oils are ethyl oleate or soybean oil) and add them to the prescribed amount of eucalyptol oil phase. Stir at 20°C for 2 hours to mix thoroughly and form a self-emulsifying concentrate. 3) Weigh out gelatin, glycerin, and water in a weight ratio of 1:0.3~0.65:0.9~1.3 to prepare the capsule shell; 4) The emulsion concentrate obtained in step 2) and the capsule shell obtained in step 3) are used to make soft capsules in a conventional manner.

[0046] The emulsifying effect of the prepared soft capsule formulation was tested, and the specific test results are shown in Table 1:

[0047] As shown in Table 1, the applicant found that the emulsification effect was poor when using a single emulsifier to prepare self-emulsifying solutions (e.g., soft capsules 7-10), resulting in ineffective dispersion of active ingredients and poor system stability. The applicant had previously discovered that adding co-emulsifiers (such as propylene glycol, diethylene glycol monoethyl ether, PEG 400, etc.) and oils (soybean oil, corn oil, ethyl oleate, or medium-chain triglycerides, etc.) could also solve the technical problem of poor emulsification with a single emulsifier. However, the resulting droplet size was too large (above 150 nm), and the capsule contents were larger after using co-emulsifiers and oils, resulting in larger capsule volumes that were difficult to swallow and reduced patient dependence (e.g., soft capsules 11-13). The applicant's research found that using a composite emulsifier not only effectively solved the technical problem of ineffective emulsification with a single emulsifier, but also resulted in smaller droplet sizes after emulsification, making the prepared capsules easier to swallow.

[0048] Example 2: Screening of Emulsifier Dosage The specific component amounts of the soft capsules prepared in this experiment are shown in Table 2, and the preparation method is as follows: 1) Weigh eucalyptol, limonene and α-pinene according to a weight ratio of 4.6:3:1, stir at 20°C for 1 hour to obtain the eucalyptol-limonene-pinene oil phase; 2) Add the prescribed amount of emulsifier or co-emulsifier to the prescribed amount of eucalyptol oil phase, stir at 20°C for 2 hours to mix evenly, and form a self-emulsifying concentrate; 3) Weigh out gelatin, glycerin, and water in a weight ratio of 1:0.3~0.65:0.9~1.3 to prepare the capsule shell; 4) The emulsion concentrate obtained in step 2) and the capsule shell obtained in step 3) are used to make soft capsules in a conventional manner.

[0049] The emulsifying effect of the prepared soft capsule formulation was tested, and the specific test results are shown in Table 2:

[0050] As shown in Table 2, the applicant further explored the dosage of the compound emulsifier and found that further reducing the dosage of the compound emulsifier (e.g., in soft capsules 14-18, the emulsifier dosage was reduced from 1.8 times the active ingredient to 0.8-1.5 times) did not affect the emulsification effect of the self-emulsifying preparation. The droplet size could be maintained at around nanometers, the dispersion time was short, and the system was stable. The reduction of excipients could result in soft capsules with smaller particle sizes, which were more conducive to swallowing and maintaining patient dependence.

[0051] Example 3 Pharmacokinetic Experiment - Rats Experimental animals and grouping: Healthy adult SD rats, weighing 200-220g, were randomly divided into 13 groups of 3 rats each. Groups 1-12 were administered the contents of the corresponding soft capsules prepared in Examples 1-2 at a dose of 150 mg / kg, respectively. Group 13 served as the control, administering the contents of commercially available eucalyptol enteric-coated capsules (trade name: Cherno®, specifically a soft capsule made of eucalyptol oil and a suitable amount of soybean oil, with a dose of 0.3g / capsule based on eucalyptol oil) at a dose of 150 mg / kg. All dosages were calculated based on eucalyptol oil.

[0052] Administration method: The medication is administered by gavage. The liquid is inserted into the oral cavity through the corner of the mouth and pushed into the esophagus along the palate wall.

[0053] Sample collection: 0.3 ml of blood was collected from the orbital cavity immediately before administration and at 5 min, 10 min, 30 min, 45 min, 1 h, 2 h, 3 h, 5 h, 7 h, and 9 h after administration. The blood samples were placed in heparin-anticoagulated EP tubes, centrifuged at 3500 r / min for 10 min, and the supernatant plasma was collected.

[0054] Sample preparation: Add the supernatant plasma to the internal standard working solution, then add n-hexane, vortex and centrifuge, and collect the supernatant.

[0055] GC-MS Analysis: The concentrations of eucalyptol, limonene, and α-pinene in the supernatant were detected using gas chromatography-mass spectrometry (GC-MS). The relative bioavailability of the experimental formulation compared to the control formulation was calculated based on the data obtained from the instrumental analysis. Specific detection results are shown in Table 3.

[0056] In the table, the range shown by Tmax represents the shortest and longest time required for the three active ingredients to reach their peak values. For example, among the three active ingredients in soft capsule 14, the shortest time to reach peak value is 0.76 hours and the longest time to reach peak value is 1.17 hours.

[0057] The applicant found that (1) the bioavailability of soft capsules 11-13 prepared by using a co-emulsifier and oil was improved compared to the control formulation, and the time to peak concentration was also shortened. (2) Compared to soft capsules 11-13, the bioavailability of soft capsules prepared by using a compound emulsifier was further improved, and the time to peak concentration was shorter. The relative bioavailability and time to peak concentration of the three active ingredients in soft capsule 21 prepared by using EL-35 as the second emulsifier were further improved. When Tween was further used as the second emulsifier (soft capsule 20), the relative bioavailability of limonene and α-pinene was more significantly improved compared to EL-35 (soft capsule 21), but the improvement of eucalyptol was not significant. (3) By optimizing the formulation composition, the applicant found that when the amount of emulsifier is 0.8 to 1.5 times that of the active ingredient (such as soft capsules 1 and 14 to 19), the bioavailability of the three active ingredients is significantly improved. In particular, soft capsules 15 to 17 not only show significant improvement in the bioavailability of the three active ingredients, but also have a shorter peak time (0.5 to 1 h), which is conducive to the rapid onset of action of the drug.

[0058] Example 4 Pharmacokinetic Experiment - Beagle

[0059] This experiment established a method for determining the concentrations of α-pinene, limonene, and eucalyptol in beagle dog biological samples using gas chromatography-mass spectrometry (GC-MS) (all dosages described below are based on eucalyptol and limonene).

[0060] Experimental drugs and dosages: Experimental formulations: Soft capsules 15 and 20 prepared in Examples 1 and 2 were administered by gavage at a dose of 120 mg / kg. Control formulation: Enteric-coated capsules of eucalyptol (trade name: Cherno®, a soft capsule made of eucalyptol oil and an appropriate amount of soybean oil, with 0.3g / capsule based on eucalyptol oil), were administered by gavage at a dose of 300mg / kg.

[0061] Animal selection: Healthy adult beagles aged 1 to 3 years and weighing 10 to 15 kg were selected as experimental subjects, ensuring they had no obvious disease symptoms, normal appetite, and good mental state. A total of 10 beagles were used in the experiment. These 10 beagles were randomly divided into three groups: the soft capsule 15 group, the soft capsule 20 group, and the control group. The soft capsule 15 group consisted of 4 beagles, the soft capsule 20 group consisted of 3 beagles, and the control group consisted of 3 beagles. Animals were fasted overnight (12-16 hours) before administration and resumed feeding 4 hours after administration. During the fasting period, animals had free access to water.

[0062] Experimental Procedure: Beagles were administered the experimental drugs via single gavage to soft capsules 15, 20, and the control formulation, respectively. Blood samples were collected at different time points after administration to determine the concentrations of α-pinene, limonene, and eucalyptol. Data were fitted and analyzed using DAS software, and statistical distance parameters were obtained through a non-compartmental model.

[0063] Blood was collected from the forelimb veins of beagle dogs using a syringe and then placed in EDTA-K2 anticoagulant blood collection tubes, which were shaken appropriately. The blood samples were placed on ice immediately after collection. Within 2 hours of collection, the samples were centrifuged (4℃, 3500 rpm, 10 min), and the supernatant plasma was collected and stored immediately at -80℃. Subsequently, it was transferred to a multi-site testing facility (Yizhuang Analytical Testing Facility) under dry ice conditions for analysis.

[0064] The blood collection time points for the experimental group are as follows: before administration (Pre-dose), 5 min, 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h after administration (the blood volume is approximately 1 mL of whole blood).

[0065] Data analysis: The concentrations of eucalyptol, limonene, α-pinene, and other components in plasma samples were determined by gas chromatography-mass spectrometry (GC-MS). Plasma concentration-time curves were plotted, and the relative bioavailability of the experimental formulation compared to the control formulation at the same dosage was calculated. The experimental results are shown in Table 4 below.

[0066]

[0067] Table 4 shows that in the beagle dog bioavailability study, the bioavailability of both soft capsules 15 and 20 was improved compared to the control formulation, especially the relative bioavailability of eucalyptol in soft capsule 15, which showed a more significant improvement. Furthermore, compared to soft capsule 20, soft capsule 15 uses less excipients, saving costs and allowing for the preparation of smaller capsules, thus improving patient compliance. The applicant found that compared to the average Tmax of 2.6 h for the three components in the control formulation, the time to peak concentration (TMC) of the soft capsule formulation was shorter, at 1.1 h for soft capsule 15 and 1.2 h for soft capsule 20 (1.1 and 1.2 represent the maximum TMC values ​​among the three groups).

[0068] In repeated-dose studies, no drug accumulation was observed in SD rats after oral gavage administration of enteric-coated eucalyptol soft capsules and soft capsule 15 (or its contents) for 26 consecutive weeks and in beagle dogs after 39 consecutive weeks. No drug accumulation was also observed in reproductive toxicity studies, juvenile toxicology studies, and accompanying toxicokinetics studies, indicating good safety with long-term administration. Based on clinical trial results, a single dose of 120 mg of the capsule formulation achieved bioavailability similar to that of commercially available enteric-coated eucalyptol soft capsules.

[0069] Example 5: Formulation stability test and disintegration time test An 18-month stability study of the soft capsule formulation (temperature 25℃±2℃ / relative humidity 60%±5%) revealed that the soft capsules exhibited superior stability at 1-6 and 14-18 months. The contents remained a pale yellow, transparent, oily liquid throughout the 0, 3, 6, 9, 12, and 18-month periods, without any color change, turbidity, or precipitation, indicating that its physical properties remained stable during long-term storage. During this period, the content of the active ingredient met the standards at all observed time points, with minimal fluctuations, demonstrating the stability of the formulation and providing a reliable guarantee for clinical application.

[0070] Meanwhile, according to the test method for disintegration time limit in General Chapter 0921 of Part IV of the 2020 edition of the Chinese Pharmacopoeia, the disintegration time limits of soft capsules at 0, 3, 6, 9, 12, and 18 months were determined for samples 1-6 and 14-18 months old. The results showed that all samples could completely disintegrate within 1 hour, indicating that they could maintain good disintegration even after long-term storage, which meets the requirements of the Chinese Pharmacopoeia.

[0071] Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention. Those skilled in the art can make changes, modifications, substitutions and variations to the above embodiments within the scope of the present invention.

Claims

1. A pharmaceutical composition, characterized in that, Including active ingredients and emulsifiers, among which, The active ingredients include eucalyptol, limonene, and α-pinene; The emulsifier is a composite emulsifier, comprising at least two types of emulsifiers; The weight ratio of the active ingredient to the emulsifier is 1:(0.8-1.5).

2. The pharmaceutical composition according to claim 1, characterized in that, The HLB value of the composite emulsifier is 13-15.

3. The pharmaceutical composition according to claim 1, characterized in that, The weight ratio of the active ingredient to the emulsifier is 1:(0.9 to 1.1), preferably 1:

1.

4. The pharmaceutical composition according to claim 1, characterized in that, The emulsifier is selected from at least two of the following: PEG-glycerol caprylate, Tween, polyoxyethylene castor oil, and polyoxyethylene hydrogenated castor oil.

5. The pharmaceutical composition according to claim 1, characterized in that, The emulsifier includes a first emulsifier and a second emulsifier; The first emulsifier is selected from polyethylene glycol glycerol octanoate and caprylic acid decanoate; The second emulsifier is selected from one or more of Tween and polyoxyethylene castor oil.

6. The pharmaceutical composition according to claim 5, characterized in that, The weight ratio of the first emulsifier to the second emulsifier is 1:1 to 3.2:1, preferably 1.8:1 to 2.3:

1.

7. The pharmaceutical composition according to claim 1, characterized in that, The weight ratio of eucalyptol, limonene and α-pinene is (3~5):(2~4):1, preferably (3~4.6):(2~3):

1.

8. The pharmaceutical composition according to claim 1, characterized in that, The pharmaceutical composition is prepared into a capsule, which may be a soft capsule or a hard capsule.

9. The pharmaceutical composition according to claim 1, characterized in that, In a unit dose of the pharmaceutical composition, the content of the active ingredient is 50-70 mg, preferably 60 mg.

10. The pharmaceutical composition according to claim 4, characterized in that, The Tween is Tween 80; and / or the polyoxyethylene castor oil is polyoxyethylene (35) castor oil.

11. A capsule, characterized in that, The capsules contain active ingredients and emulsifiers; The active ingredients include eucalyptol, limonene, and α-pinene; The active ingredient content in a unit dose of capsules is 50~70mg.

12. The capsule as described in claim 11, characterized in that, The emulsifier is selected from at least two of the following: glyceryl caprylate, octanoate, Tween, polyoxyethylene castor oil, and polyoxyethylene hydrogenated castor oil.

13. The capsule as described in claim 12, characterized in that, The emulsifier includes a first emulsifier and a second emulsifier; The first emulsifier is selected from polyethylene glycol glycerol octanoate and caprylic acid decanoate; The second emulsifier is selected from one or more of Tween and polyoxyethylene castor oil.

14. The capsule as described in claim 13, characterized in that, The Tween is Tween 80; and / or the polyoxyethylene castor oil is polyoxyethylene (35) castor oil.

15. The capsule as described in claim 11, characterized in that, The capsules satisfy one or more of the characteristics in (a) to (d): (a) The weight ratio of eucalyptol, limonene, and α-pinene is (3~5):(2~4):1, preferably (3~4.6):(2~3):1; (b) The weight ratio of the active ingredient to the emulsifier is 1:(0.8–1.5); preferably 1:(0.9–1.1), more preferably 1:1; (c) The active ingredient content in a unit dose of capsule is 60 mg; (d) The capsule is a soft capsule or a hard capsule.

16. Use of the pharmaceutical composition according to any one of claims 1 to 10 or the capsule according to any one of claims 11 to 15 in the preparation of a medicament, wherein the medicament is used to relieve cough, reduce inflammation, expectorate, promote the excretion of contrast agents, or treat respiratory diseases; wherein the respiratory diseases are preferably selected from at least one of acute sinusitis, chronic sinusitis, acute bronchitis, chronic bronchitis, pneumonia, lung abscess, chronic obstructive pulmonary disease, pulmonary fungal infection, pulmonary tuberculosis, silicosis, and pulmonary interstitial fibrosis.

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