Lung anti-inflammatory spray based on aloe polysaccharide and preparation method thereof

Abstract

The invention relates to the technical field of medicines, and discloses a lung anti-inflammatory spray based on aloe polysaccharide, which realizes efficient anti-inflammatory (IL-6) and targeted delivery (deposition rate of 85%) by optimizing the proportion of natural components (8% of aloe polysaccharide, 1.5% of dipotassium glycyrrhizinate and 2% of andrographolide) and an atomization process (particle size of 2 mu m). According to the lung anti-inflammatory spray based on the aloe polysaccharide and the preparation method of the lung anti-inflammatory spray, through the synergistic effect of the aloe polysaccharide (8%) and natural anti-inflammatory components (1.5% of dipotassium glycyrrhizinate and 2% of andrographolide), the proinflammatory factor level (IL-6 is reduced by 60%, and TNF-alpha is reduced by 62%) is remarkably reduced, the inhibition rate on an LPS-induced mouse pneumonia model reaches 88% or above, and the lung anti-inflammatory spray has the advantages that the lung anti-inflammatory spray has a good application prospect. The effect of the dexamethasone spray is better than that of a single-component or chemically synthesized drug (such as dexamethasone), drug particles are efficiently deposited in an alveolar area through an optimized atomization process (the spraying particle size is 2 microns), the lung deposition rate is larger than or equal to 85% and far exceeds that of a conventional spray (generally smaller than or equal to 70%), and the bioavailability is remarkably improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medicine, in particular to a lung anti-inflammatory spray based on aloe polysaccharide and a preparation method thereof, which is suitable for the auxiliary treatment of chronic bronchitis, asthma and other respiratory tract inflammation. BACKGROUND

[0002] In the prior art, lung anti-inflammatory drugs mainly rely on chemical synthetic drugs such as glucocorticoids (such as dexamethasone), which have a certain anti-inflammatory effect, but long-term use can easily lead to immune suppression, osteoporosis and other serious side effects. Although natural anti-inflammatory ingredients (such as aloe polysaccharide) are safer, they are difficult to achieve effective lung-targeted therapy due to their large molecular weight, poor stability, low alveolar absorption efficiency and other problems. In addition, the particle size distribution of the traditional spray process cannot be precisely controlled (usually > 5 μm), resulting in insufficient drug lung deposition rate (≤ 70%), which severely limits the bioavailability. Therefore, it is urgent to develop a natural source lung anti-inflammatory spray with high efficiency, precise delivery and long-term safety. SUMMARY

[0003] (I) Technical problems solved

[0004] In view of the deficiencies of the prior art, the present application provides a lung anti-inflammatory spray based on aloe polysaccharide and a preparation method thereof, which has the advantages of natural ingredient compounding to achieve anti-inflammatory effect comparable to chemical drugs, avoiding side effects, optimizing the spray process to improve the drug lung deposition rate, and ensuring the activity and stability of aloe polysaccharide through stabilizers and process design. The problems of large molecular weight, poor stability, low alveolar absorption efficiency and other problems of natural anti-inflammatory ingredients are solved.

[0005] (II) Technical solutions

[0006] To achieve the above-mentioned enhanced anti-inflammatory effect and improved absorption and stability, the present application provides the following technical solutions: a lung anti-inflammatory spray based on aloe polysaccharide, characterized in that it is composed of the following components in weight percentage:

[0007] · Aloe polysaccharide 0.5%-15%

[0008] · Anti-inflammatory adjuvant 0.1%-10%

[0009] · Penetration enhancer 0.1%-5%

[0010] · Stabilizer 0.05%-3%

[0011] · Isotonicity regulator 0.5%-8%

[0012] · The balance is sterile water or physiological saline.

[0013] Preferably, the anti-inflammatory adjuvant drug is any one or a combination of the following:

[0014] • Dipotassium glycyrrhizinate 0.1%-3%

[0015] • Andrographolide 0.2%-5%

[0016] • Baicalin 0.3%-6%

[0017] • Dexamethasone 0.01%-1% (chemically synthesized drug).

[0018] Preferably, the preferred concentration of aloe polysaccharide is 5%-10%, within which the anti-inflammatory effect is optimal, manifested by a 40%-60% reduction in lung IL-6 and TNF-α levels.

[0019] Preferably, when the concentration of aloe polysaccharide is 8%, dipotassium glycyrrhizinate is 1.5%, and andrographolide is 2%, the synergistic anti-inflammatory effect is optimal, with an inhibition rate of more than 85% on the LPS-induced mouse pneumonia model.

[0020] Preferably, the penetration enhancer is polysorbate 80 (0.2%-2%) or azone (0.1%-1%) for enhancing alveolar mucosa absorption.

[0021] Preferably, the stabilizer is trehalose (0.1%-2%) or mannitol (0.5%-3%) for maintaining aloe polysaccharide activity.

[0022] Preferably, the isotonicity regulator is sodium chloride (0.5%-5%) or glucose (1%-8%).

[0023] Another technical problem to be solved by the present application is to provide a lung anti-inflammatory spray and a preparation method thereof, comprising the following steps:

[0024] (1) Aloe polysaccharide extraction: after crushing aloe gel, cellulase hydrolysis, ethanol precipitation, and dialysis purification, aloe polysaccharide with a purity of ≥90% is obtained; (2) Mixing and dissolving: under sterile conditions at 40-50°C, aloe polysaccharide and anti-inflammatory adjuvant drugs are dissolved in part of sterile water, and stirred until completely dissolved; (3) Add excipients: add penetration enhancer, stabilizer, and isotonicity regulator in turn, and stir to mix evenly; (4) Volume adjustment and filtration: supplement sterile water to the full amount, and filter through a 0.22 μm microporous filter to remove bacteria; (5) Subpackaging and quality inspection: fill into a spray device, seal with nitrogen, and perform pH (5.5-7.0), osmotic pressure (280-320 mOsm / kg), and sterility detection.

[0025] Preferably, the ethanol precipitation in step (1) uses an ethanol concentration of 60%-80%, and a dialysis bag with a molecular weight cutoff of 3kDa is used during dialysis.

[0026] Preferably, the stirring speed in step (3) is 200-400 rpm and the mixing time is not less than 30 minutes.

[0027] Preferably, the spraying device in step (5) is a metering atomizing pump, and the sprayed particle size is controlled at 1-10 μm to ensure that the lung deposition rate is ≥70%.

[0028] (III) Beneficial Effects

[0029] Compared with the prior art, the present invention provides a lung anti-inflammatory spray based on aloe polysaccharides and its preparation method, which has the following beneficial effects:

[0030] 1. This lung anti-inflammatory spray based on aloe polysaccharide and its preparation method significantly reduce the levels of pro-inflammatory factors (IL-6 reduced by 60% and TNF-α reduced by 62%) through the synergistic effect of aloe polysaccharide (8%) and natural anti-inflammatory components (dipotassium glycyrrhizate 1.5% and andrographolide 2%). The inhibition rate of LPS-induced mouse pneumonia model is over 88%, which is superior to the effect of single components or chemically synthesized drugs (such as dexamethasone).

[0031] 2. The aloe polysaccharide-based anti-inflammatory lung spray and its preparation method, through an optimized atomization process (spray particle size 2μm), enable drug particles to be efficiently deposited in the alveolar region, with a lung deposition rate of ≥85%, far exceeding that of conventional sprays (usually ≤70%), significantly improving bioavailability.

[0032] 3. This lung anti-inflammatory spray based on aloe polysaccharides and its preparation method, by using natural ingredients as the main component, avoids the side effects (such as immunosuppression) of chemically synthesized drugs (such as glucocorticoids), making it suitable for long-term use; the excipients (such as trehalose and polysorbate 80) are all pharmaceutical-grade safe ingredients. Attached Figure Description

[0033] Fig. 1 This is a flow chart of the spray preparation process proposed in this invention;

[0034] Fig. 2 This is a comparison chart showing the effects of different formulations proposed in this invention on IL-6 levels;

[0035] Fig. 3 This is a comparison diagram of the spray particle size distribution proposed in this invention. Detailed Implementation

[0036] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0037] Please see Figs. 1-3 This invention discloses a lung anti-inflammatory spray based on aloe polysaccharides and its preparation method. The core innovation lies in achieving highly efficient anti-inflammatory effects and precise lung delivery through the synergistic action of specific components and optimized process parameters. Specific features and their mechanism of action are as follows:

[0038] 1. Mechanism of action of the formulation components

[0039] • Aloe polysaccharide (8%): ​​As a core anti-inflammatory component, it reduces the expression of pro-inflammatory factors such as IL-6 and TNF-α by inhibiting the NF-κB signaling pathway. A concentration range of 5-10% is preferred to balance efficacy and safety, with peak activity achieved at 8%.

[0040] • Dipotassium glycyrrhizate (1.5%) and andrographolide (2%): synergistically enhance anti-inflammatory effects. The former inhibits cyclooxygenase (COX-2), and the latter blocks the release of inflammatory mediators. The combination of the three increases the inhibition rate of LPS-induced pneumonia to 88%.

[0041] • Permeation enhancer (polysorbate 80 1%): Improves drug transmembrane permeability by disrupting the structure of the alveolar mucus layer.

[0042] • Stabilizer (trehalose 1%): Forms hydrogen bonds with aloe polysaccharide molecules to prevent polysaccharide degradation during high temperatures or long-term storage.

[0043] 2. Scientific basis for process parameters

[0044] • Ethanol precipitation (75% concentration) and dialysis (3kDa cutoff): Ensure polysaccharide purity ≥90%, remove small molecule impurities (such as aloe-emodin), and avoid irritating the respiratory tract.

[0045] • Atomized particle size control (2μm): Based on the alveolar deposition dynamics model, a particle size of 1-5μm can ensure a deposition rate of over 70%, and 2μm is the optimal solution (deposition rate of 85%).

[0046] • Stirring speed (400 rpm) and time (60 minutes): Through fluid dynamics simulation, this combination of parameters can achieve a system homogeneity of over 98%.

[0047] 3. Route of administration and absorption mechanism

[0048] This spray is administered via oral inhalation, using a metered-dose nebulizer (2 μm particle size) to ensure drug particle deposition in the alveolar region (1-5 μm is the optimal deposition range). The addition of the penetration enhancer polysorbate 80 (1%) enhances absorption through the following mechanisms:

[0049] • It disrupts the structure of the mucus layer on the surface of the alveoli and reduces the viscoelasticity of the mucus;

[0050] • Increases the transmembrane permeability of aloe polysaccharides (verified in an in vitro alveolar epithelial cell model, the permeation efficiency is increased by approximately 50%).

[0051] Based on

[0052] • Reference: J Aerosol Med Pulm Drug Deliv. 2020;33(4):179-190 (Relationship between atomized particle size and deposition rate).

[0053] 4. Anti-inflammatory mechanism of aloe polysaccharides

[0054] Aloe polysaccharides (purity ≥90%) downregulate the expression of pro-inflammatory factors such as IL-6 and TNF-α by inhibiting the NF-κB signaling pathway (see...). Fig. 3 Its anti-inflammatory effect on the lungs was verified by the following experiments:

[0055] In vitro experiments: In LPS-induced RAW264.7 macrophages, aloe polysaccharide (8%) reduced IL-6 secretion by 58% (p<0.01).

[0056] In vivo experiments: In a mouse pneumonia model induced by LPS, the IL-6 level in the bronchoalveolar lavage fluid of the spray group was reduced by 60%, and there was no thymic atrophy (compared to the immunosuppressive side effects of the dexamethasone group).

[0057] Example 1:

[0058] 1. Formula composition:

[0059] • Aloe polysaccharides: 5%

[0060] Dipotassium glycyrrhizate: 1%

[0061] Polysorbate 80: 0.5%

[0062] Trehalose: 0.5%

[0063] Sodium chloride: 2%

[0064] The remaining amount is sterile water.

[0065] 2. Preparation method:

[0066] 1> Aloe polysaccharide extraction: Precipitation with 70% ethanol followed by dialysis purification (molecular weight cutoff 3kDa).

[0067] 2> Mixed Dissolution: Dissolve aloe polysaccharides and dipotassium glycyrrhizate at 45℃.

[0068] 3> Add auxiliary materials: Add other auxiliary materials in sequence, stir at 300 rpm, and mix for 40 minutes.

[0069] 4> Volume adjustment and filtration: Sterilization is achieved through a 0.22μm microporous membrane.

[0070] 5> Packaging and Quality Inspection: Sprayed particle size 5μm, pH 6.2, osmotic pressure 290 mOsm / kg.

[0071] 3. Results Data:

[0072] In an LPS-induced mouse pneumonia model, IL-6 levels decreased by 45% and TNF-α levels decreased by 50%.

[0073] • The lung deposition rate was 72%.

[0074] Example 2:

[0075] 1. Formula composition:

[0076] • Aloe polysaccharides: 8%

[0077] Andrographolide: 2%

[0078] • Azone: 0.3%

[0079] Mannitol: 1%

[0080] • Glucose: 4%

[0081] The remainder is physiological saline.

[0082] 2. Preparation method:

[0083] 1> Aloe polysaccharide extraction: Precipitation with 65% ethanol followed by dialysis purification (molecular weight cutoff 3kDa).

[0084] 2> Mixed Dissolution: Dissolve aloe polysaccharides and andrographolide at 50℃.

[0085] 3> Add auxiliary materials: Add other auxiliary materials in sequence, stir at 350 rpm, and mix for 50 minutes.

[0086] 4> Volume adjustment and filtration: Sterilization is achieved through a 0.22μm microporous membrane.

[0087] 5> Packaging and Quality Inspection: Sprayed particle size 3μm, pH 6.5, osmotic pressure 310 mOsm / kg.

[0088] 3. Results Data:

[0089] • IL-6 levels decreased by 55%, and TNF-α levels decreased by 58%.

[0090] • It achieved an 80% inhibition rate against LPS-induced pneumonia and a 78% lung deposition rate.

[0091] Example 3:

[0092] 1. Formula composition:

[0093] • Aloe polysaccharides: 8%

[0094] Dipotassium glycyrrhizate: 1.5%

[0095] Andrographolide: 2%

[0096] Polysorbate 80: 1%

[0097] Trehalose: 1%

[0098] Sodium chloride: 3%

[0099] The remaining amount is sterile water.

[0100] 2. Preparation method:

[0101] 1> Aloe polysaccharide extraction: Precipitation with 75% ethanol followed by dialysis purification (molecular weight cutoff 3kDa).

[0102] 2> Mixing and Dissolving: Dissolve aloe polysaccharides and auxiliary drugs at 48℃.

[0103] 3> Add auxiliary materials: Add other auxiliary materials in sequence, stir at 400 rpm, and mix for 60 minutes.

[0104] 4> Volume adjustment and filtration: Sterilization is achieved through a 0.22μm microporous membrane.

[0105] 5> Packaging and Quality Inspection: Sprayed particle size 2μm, pH 6.0, osmotic pressure 300 mOsm / kg.

[0106] 3. Results Data:

[0107] • IL-6 levels decreased by 60%, and TNF-α levels decreased by 62%.

[0108] • It achieved an 88% inhibition rate against LPS-induced pneumonia and a 85% lung deposition rate.

[0109] Experimental example:

[0110] Data Analysis and Comparison:

[0111] 1. Anti-inflammatory effect:

[0112] • The reduction in IL-6 and TNF-α in Example 3 was significantly higher than that in the other two groups, indicating that the synergistic effect of aloe polysaccharide (8%) with dipotassium glycyrrhizate (1.5%) and andrographolide (2%) was the strongest.

[0113] • The optimized ratio of penetration enhancer (polysorbate 80) and stabilizer (trehalose) further improves drug stability and absorption efficiency.

[0114] 2. Lung deposition rate:

[0115] • The ejection particle size (2 μm) of Example 3 is closer to the optimal deposition range of alveoli (1-5 μm), and therefore the deposition rate is the highest (85%).

[0116] 3. Preparation process:

[0117] • A high stirring speed (400 rpm) and mixing time (60 minutes) ensure uniform dispersion of components and improve the consistency of drug efficacy.

[0118] Judgment criteria: The formulation (8% aloe polysaccharide + 1.5% dipotassium glycyrrhizate + 2% andrographolide) and preparation process of Example 3 are the best schemes, and their anti-inflammatory effects, lung deposition rate and process stability are significantly better than those of other examples.

[0119] The beneficial effects of this invention are:

[0120] 1. Highly effective anti-inflammatory: Through the synergistic effect of aloe polysaccharides and natural anti-inflammatory components, it significantly reduces the levels of pro-inflammatory factors (IL-6, TNF-α).

[0121] 2. Targeted delivery: Optimized spray particle size (1-10μm) ensures efficient drug deposition in the lungs, improving bioavailability.

[0122] 3. High safety: It is mainly composed of natural ingredients, reducing the risk of side effects from chemically synthesized drugs (such as dexamethasone).

[0123] 4. Stable process: Strict preparation parameters (such as dialysis purification and aseptic filtration) ensure product consistency and safety.

[0124] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A lung anti-inflammatory spray based on aloe polysaccharides, characterized in that, It consists of the following components by weight percentage: Aloe polysaccharides 0.5%-15% • Anti-inflammatory adjuvant drugs 0.1%-10% • Penetration enhancer 0.1%-5% Stabilizer 0.05%-3% • Isotonic conditioner 0.5%-8% The remainder is sterile water or physiological saline.

2. The lung anti-inflammatory spray according to claim 1, characterized in that, The anti-inflammatory adjuvant drug is any one or a combination of the following: Dipotassium glycyrrhizate 0.1%-3% Andrographolide 0.2%-5% Baicalin 0.3%-6% • Dexamethasone 0.01%-1% (chemically synthesized drug).

3. The lung anti-inflammatory spray according to claim 1 or 2, characterized in that, The preferred concentration of the aloe polysaccharide is 5%-10%, within which the anti-inflammatory effect is best, manifested by a 40%-60% reduction in lung IL-6 and TNF-α levels.

4. The lung anti-inflammatory spray according to claim 3, characterized in that, The synergistic anti-inflammatory effect was optimal when the concentrations of aloe polysaccharide were 8%, dipotassium glycyrrhizate were 1.5%, and andrographolide were 2%.

5. The lung anti-inflammatory spray according to claim 1, characterized in that, The penetration enhancer is polysorbate 80 (0.2%-2%) or azone (0.1%-1%), used to enhance alveolar mucosal absorption.

6. The lung anti-inflammatory spray according to claim 1, characterized in that, The stabilizer is trehalose (0.1%-2%) or mannitol (0.5%-3%), used to maintain the activity of aloe polysaccharides.

7. The lung anti-inflammatory spray according to claim 1, characterized in that, The isotonic regulator is sodium chloride (0.5%-5%) or glucose (1%-8%).

8. A lung anti-inflammatory spray according to any one of claims 1-7 and a method for preparing the same, characterized in that, Includes the following steps: (1) Extraction of aloe polysaccharides: After pulverizing aloe gel, aloe polysaccharides with a purity of ≥90% were obtained by enzymatic hydrolysis of cellulose, ethanol precipitation and dialysis purification. (2) Mixing and dissolving: Dissolve aloe polysaccharides and anti-inflammatory adjuvant drugs in a portion of sterile water under sterile conditions at 40-50℃, and stir until completely dissolved; (3) Addition of excipients: Add the penetration enhancer, stabilizer and isotonicity regulator in sequence, and stir to mix evenly; (4) Volume adjustment and filtration: Add sterile water to the full volume and filter through a 0.22μm microporous membrane for sterilization; (5) Packaging and quality inspection: Fill into a spray device, seal with nitrogen, and perform pH (5.5-7.0), osmotic pressure (280-320mOsm / kg) and sterility tests.

9. The preparation method according to claim 8, characterized in that, The ethanol precipitation in step (1) uses an ethanol concentration of 60%-80%, and a dialysis bag with a molecular weight cutoff of 3kDa is used during dialysis.

10. The preparation method according to claim 8, characterized in that, In step (3), the stirring speed is 200-400 rpm and the mixing time is no less than 30 minutes.

11. The preparation method according to claim 8, characterized in that, The spraying device in step (5) is a metered atomizing pump, and the sprayed particle size is controlled between 1-10 μm to ensure that the lung deposition rate is ≥70%.

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