A saline-based nasal wash aerosol and method of making same

Abstract

This invention relates to nasal care aerosols, specifically disclosing a saline-based nasal rinse aerosol and its preparation method. The nasal rinse aerosol comprises, by weight percentage: 30-40% nasal rinse agent and 60-70% propellant; wherein the nasal rinse agent is prepared by mixing saline, propylene glycol, β-glucan, and pH buffer in a mass ratio of 100:(3-5):(0.1-0.3):(2-5). This invention, by adding propylene glycol to saline, can alleviate discomfort such as cold stimulation and acute spasms caused by the nasal rinse aerosol; by utilizing the water-locking and penetrating properties of β-glucan to relieve nasal dryness and effectively constrict dilated nasal capillaries, thus clearing nasal congestion; and by using the pH buffer to adjust the nasal rinse solution to a weakly acidic state, reducing the irritation of saline to the nasal cavity and better maintaining the barrier function of the nasal mucosa.

Description

Technical Field

[0001] This invention relates to nasal care aerosols, specifically to a saline-based nasal rinse aerosol and its preparation method. Background Technology

[0002] Nasal mucus often accumulates, causing dust, pollen, and other foreign objects to trap and accumulate in the nasal cavity. This not only obstructs the nasal passages but also increases the risk of allergens and respiratory infections. Nasal cleaning and care can improve the nasal cavity's moisture environment, reduce nasal congestion or crusting, and reduce the long-term adhesion of pathogens to the nasal mucosa. This can effectively relieve nasal discomfort caused by allergies or inflammation.

[0003] Currently, 0.9% isotonic saline solution is mostly used for nasal cavity cleaning. Saline solution moisturizes the nasal mucosa and relieves nasal dryness and discomfort. During nasal cleaning, a nasal irrigator is used to force the saline solution into the nostrils under pressure, allowing it to diffuse into the nasal vestibule, sinuses, and nasal passages, and then drain from the other nostril or the mouth. This cleaning method is extremely inconvenient and causes strong irritation to the nasal cavity.

[0004] To address this issue, researchers aimed to develop a saline nasal rinse into an aerosol spray for nasal cleaning. This would be convenient to carry and use anytime, anywhere, and the extended nozzle could reach deep into the nasal cavity for thorough cleaning. However, the nasal mucosa is delicate, and even slight irritation can cause redness and damage. Plain saline solution can irritate the nasal cavity, especially when the rinse is sprayed as an aerosol. The high-pressure nitrogen gas rapidly evaporates upon contact with the nasal mucosa, absorbing heat from the surrounding environment and causing a drop in local temperature. This cold stimulation can easily trigger nasal spasms and discomfort. Summary of the Invention

[0005] To overcome the cold stimulation of saline solution when rinsing the nasal cavity with an aerosol spray and to quickly relieve the discomfort of nasal dryness and nasal congestion caused by capillary dilation, this invention provides a saline-based nasal rinse aerosol and its preparation method.

[0006] The specific plan is as follows: A saline-based nasal rinse aerosol comprises, by weight percentage: 30-40% nasal rinse agent and 60-70% propellant; wherein: The nasal wash solution is prepared by mixing physiological saline, propylene glycol, β-glucan, and pH buffer in a mass ratio of 100:(3~5):(0.1~0.3):(2~5); The saline solution is medical saline solution with a sodium chloride concentration of 0.90%. The β-glucan is a soluble β-glucan with a purity >90% and a molecular weight range of 300~1000kDa; The pH buffer solution is a citrate-sodium citrate buffer solution with a pH of 5.0; The propellant is medical-grade compressed nitrogen with a purity >99.9%.

[0007] Propylene glycol does not have a noticeable cold sensation at low temperatures, and when added to saline solution, it can soothe the cold stimulation of the nasal cavity caused by the low temperature of nasal irrigation aerosols. In addition, propylene glycol has good water solubility, lubrication and moisturizing properties, which can effectively enhance the nasal irrigation effect and keep the nasal cavity clear and moist.

[0008] Preferably, the β-glucan is a soluble oat β-glucan with a purity >90% and a molecular weight of 300~1000kDa. β-glucan has abundant hydrophilic groups, is green, safe, and non-irritating, and can create a water-locking environment in the nasal cavity, maintaining long-term nasal moisture and soothing the sensitivity and irritation to the mucous membranes caused by saline nasal irrigation. Soluble oat β-glucan has good transdermal penetration ability, can quickly penetrate the nasal mucosa, constrict dilated capillaries in the nasal cavity, and relieve nasal congestion and dryness caused by respiratory infections, allergic rhinitis, etc.

[0009] Preferably, by controlling the amount of pH buffer solution used, the pH of the nasal rinse is adjusted to a slightly acidic state of 6.0-6.5. The normal pH environment of the nasal cavity is slightly acidic, which helps inhibit the growth of pathogenic microorganisms and maintain the barrier function of the nasal mucosa. By adjusting the nasal rinse to a slightly acidic environment, it becomes closer to the nasal cavity environment, is gentler on the nasal cavity, and effectively relieves irritation to the nasal cavity.

[0010] This invention relates to a method for preparing a nasal rinse aerosol based on physiological saline. The specific preparation method is as follows: S1. Weigh physiological saline according to the mixing ratio, and keep it at a constant temperature of 80°C in a water bath; then add propylene glycol and β-glucan, stir at a low speed of 50-100 rpm for 30-45 min, and then stir at a high speed of 800-1200 rpm for 25-30 min to obtain a clear solution; add pH buffer to the clear solution to adjust it to weak acidity, filter, and obtain nasal wash solution; S2. The nasal rinse solution is metered and filled into an aluminum can, the valve is installed and tightened, and the propellant is filled. According to the weight percentage composition, the nasal rinse solution contains 30-40% and the propellant contains 60-70%. The pressure inside the aluminum can is tested to be within the range of 0.65MPa-0.80MPa. After weighing and water bath testing, a 70° arc-shaped long nozzle and a top cover are installed to obtain a nasal rinse aerosol based on physiological saline.

[0011] The preparation and filling of the nasal aerosol are completed in a 100,000-level GMP clean production line. In addition to the requirements for environmental dust particles, the workshop air exchange rate must be strictly controlled to be ≥20 times / hour and the airborne bacteria count ≤500 / m³.

[0012] Compared with the prior art, the beneficial effects of the present invention are reflected in: (1) When conventional saline nasal spray is applied to the nasal cavity, it will cause instantaneous low temperature cold stimulation. This invention adds propylene glycol to the saline solution. Propylene glycol does not have a significant cold sensation at low temperatures. By using propylene glycol, the discomfort caused by the nasal spray to the nasal cavity, such as cold stimulation and emergency spasm, can be relieved.

[0013] (2) The nasal spray of the present invention is formulated with β-glucan based on physiological saline. β-glucan’s water-locking and penetrating properties relieve discomfort caused by nasal dryness and crusting, and can effectively constrict dilated capillaries in the nasal cavity. It has a good cleaning and unblocking effect on nasal congestion and swelling caused by allergic rhinitis, colds, runny nose, etc.

[0014] (3) The nasal rinse aerosol of the present invention is formulated with a pH buffer solution based on physiological saline. The pH buffer solution is used to adjust the nasal rinse solution to a weakly acidic state, which matches the normal acid-base environment of the nasal cavity, reduces the stimulation of physiological saline on the nasal cavity, can better maintain the barrier function of the nasal mucosa, and inhibit the adhesion and growth of pathogenic microorganisms on the nasal mucosa. Detailed Implementation

[0015] The following detailed description, in conjunction with embodiments, comparative examples, and evaluations of the nasal wash aerosol's effectiveness, further illustrates this application. These embodiments are merely illustrative of the invention and should not be construed as limiting its scope. All raw materials used in this application are medical-grade and commercially available. The formulation and bottling processes utilize a 100,000-level GMP-certified automated filling line.

[0016] Example 1 S1. Prepare a cleanroom. The preparation and filling of the nasal aerosol must be completed in a 100,000-level GMP cleanroom production line. In addition to requirements for environmental dust particles, the air exchange rate in the workshop must be strictly controlled to be ≥20 times / hour, and the airborne bacteria count ≤500 CFU / m³. Weigh 100 kg of medical physiological saline with a sodium chloride concentration of 0.90% and add it to a stainless steel tank. Keep the water bath temperature constant at 80°C. Then add 5 kg of propylene glycol and 0.1 kg of β-glucan (β-glucan is soluble oat β-glucan with a purity >90% and a molecular weight of 300~1000kDa). Stir at a low speed of 50 rpm for 45 min, and then stir at a high speed of 1000 rpm for 25 min to obtain a clear liquid. Add 4.2 kg of citrate-sodium citrate buffer solution with a pH of 5.0 to the clear liquid to adjust the pH to a weakly acidic 6.0. Filter to obtain the nasal wash. S2. The nasal rinse solution is metered and filled into an aluminum can, the valve is installed and tightened, and the propellant (medical compressed nitrogen with a purity > 99.9%) is filled. According to the weight percentage, the nasal rinse solution contains 35% and the propellant contains 65%. The pressure inside the aluminum can is tested to be within the range of 0.75 MPa. After weighing and water bath testing, a 70° arc-shaped long nozzle and a top cover are installed to obtain a nasal rinse aerosol based on physiological saline.

[0017] Example 2 S1. Prepare a cleanroom. The preparation and filling of the nasal aerosol must be completed in a 100,000-level GMP cleanroom production line. In addition to requirements for environmental dust particles, the air exchange rate in the workshop must be strictly controlled to be ≥20 times / hour, and the airborne bacteria count ≤500 CFU / m³. Weigh 100 kg of medical physiological saline with a sodium chloride concentration of 0.90% and add it to a stainless steel tank. Keep the water bath temperature constant at 80°C. Then add 3 kg of propylene glycol and 0.3 kg of β-glucan (β-glucan is soluble oat β-glucan with a purity >90% and a molecular weight of 300~1000kDa). Stir at a low speed of 50 rpm for 30 min, and then stir at a high speed of 1200 rpm for 30 min to obtain a clear liquid. Add 3.0 kg of citrate-sodium citrate buffer solution with a pH of 5.0 to the clear liquid to adjust the pH to a weakly acidic 6.3. Filter to obtain the nasal wash. S2. The nasal rinse solution is metered and filled into an aluminum can, the valve is installed and tightened, and the propellant (medical compressed nitrogen with a purity > 99.9%) is filled. According to the weight percentage, the nasal rinse solution contains 40% and the propellant contains 60%. The pressure inside the aluminum can is tested to be within the range of 0.70 MPa. After weighing and water bath testing, a 70° arc-shaped long nozzle and a top cover are installed to obtain a nasal rinse aerosol based on physiological saline.

[0018] Comparative Example 1 The aerosol was prepared according to the scheme of Example 1, except that propylene glycol was omitted when preparing the nasal rinse.

[0019] Comparative Example 2 The aerosol was prepared according to the scheme of Example 1, except that β-glucan was omitted when preparing the nasal rinse.

[0020] Comparative Example 3 The aerosol was prepared according to the scheme of Example 1, except that the pH buffer solution was omitted when preparing the nasal rinse.

[0021] Evaluation of the effectiveness of nasal irrigation aerosol: (a) Trial group Fifty subjects with varying degrees of nasal dryness, nasal congestion due to colds, and nasal redness and swelling due to rhinitis were randomly assigned to groups of 10, numbered 1#, 2#, 3#, 4#, and 5#. Each group tested one of the five batches of nasal rinse aerosols obtained from Example 1, Example 2, Comparative Example 1, Comparative Example 2, and Comparative Example 3. The effectiveness of the trial was evaluated after three days of use (subjects were considered to have used the aerosol at least three times a day for the trial to be considered effective).

[0022] (II) Evaluation Criteria Relief from cold stimulation score: obvious cold stimulation (0-2 points), moderate cold stimulation (4-6 points), mild cold stimulation (8-10 points). Relief from burning sensation rating: obvious burning sensation (0-2 points), moderate burning sensation (4-6 points), mild burning sensation (8-10 points). Nasal hydration effect rating: Nasal dryness persists (0-2 points), nasal dryness disappears (4-6 points), nasal hydration (8-10 points); Nasal congestion relief score: persistent nasal congestion (0-2 points), reduced nasal congestion (4-6 points), nasal congestion completely disappears (8-10 points).

[0023] (iii) Collect the evaluation results of each group of trial users, as shown in Tables 1-5.

[0024] Table 1: Evaluation of the effects of the nasal rinse aerosol in Example 1 on the trial results of Group 1# trial participants Table 2: Evaluation of the effects of the nasal rinse aerosol in Example 2 on the trial participants in Group 2# As shown in Tables 1 and 2 of the trial effect evaluation of Examples 1 and 2 above, the nasal rinse aerosol of the present invention, by adjusting propylene glycol, β-glucan, and pH buffer to the basic saline solution, makes the nasal rinse aerosol milder, less prone to cold or burning stimulation, and keeps the nasal cavity moist, effectively constricting dilated capillaries in the nasal cavity to relieve nasal congestion. From the formulation schemes of Examples 1 and 2, it can be seen that when the amount of propylene glycol in Example 2 was reduced, a certain degree of cold stimulation occurred. Clearly, propylene glycol is effective in alleviating the cold stimulation of saline aerosol spray. Increasing the amount of β-glucan in Example 2 is more effective in maintaining nasal cavity moisture, soothing the burning and sensitive irritation to the mucous membrane during saline nasal rinsing, and relieving nasal congestion.

[0025] Table 3: Evaluation of the effects of the nasal rinse aerosol on the control group 1 in group 3# Table 4: Evaluation of the effects of the nasal rinse aerosol on comparative example 2 by trial participants in group #4 Table 5: Evaluation of the effects of nasal rinse aerosol on comparative example 3 by trial participants in group 5# As can be seen from Tables 3, 4, and 5, which evaluate the trial effects of Comparative Examples 1, 2, and 3, omitting propylene glycol in the preparation of the nasal rinse solution (Table 3) resulted in a significant cold irritation in the nasal rinse aerosol; omitting β-glucan in the preparation of the nasal rinse solution (Table 4) significantly reduced the nasal humidification and nasal congestion relief effects of the nasal rinse aerosol; and omitting pH buffer solution in the preparation of the nasal rinse solution (Table 5) reduced the gentleness of the nasal rinse aerosol and resulted in a certain burning sensation.

[0026] Through the evaluation of the trial effects of the above embodiments and comparative examples, those skilled in the art should understand that the present invention, by adjusting propylene glycol, β-glucan, and pH buffer solution on the basis of physiological saline, exhibits a significant synergistic effect and represents outstanding progress. Any minor adjustments or modifications, or equivalent substitutions made based on the technical solutions described in the foregoing description and embodiments should be included within the scope of protection of this invention.

Claims

1. A nasal rinse aerosol based on physiological saline, characterized in that, The nasal rinse aerosol comprises, by weight percentage: 30-40% nasal rinse agent and 60-70% propellant; wherein: The nasal wash solution is prepared by mixing physiological saline, propylene glycol, β-glucan, and pH buffer in a mass ratio of 100:(3~5):(0.1~0.3):(2~5); The saline solution is medical saline solution with a sodium chloride concentration of 0.90%. The β-glucan is a soluble β-glucan with a purity >90% and a molecular weight range of 300~1000kDa; The pH buffer solution is a citrate-sodium citrate buffer solution with a pH of 5.0; The propellant is medical compressed nitrogen with a purity >99.9%.

2. The nasal irrigation aerosol based on physiological saline according to claim 1, characterized in that: The β-glucan is a soluble oat β-glucan with a purity >90% and a molecular weight of 300~1000kDa.

3. The nasal irrigation aerosol based on physiological saline according to claim 1, characterized in that: By controlling the amount of pH buffer solution used, the pH of the nasal rinse can be adjusted to a weakly acidic state of 6.0-6.

5.

4. A method for preparing a nasal rinse aerosol based on physiological saline as described in any one of claims 1 to 3, characterized in that, The specific preparation method is as follows: S1. Weigh physiological saline according to the mixing ratio, and keep it at a constant temperature of 80°C in a water bath; then add propylene glycol and β-glucan, stir at a low speed of 50-100 rpm for 30-45 min, and then stir at a high speed of 800-1200 rpm for 25-30 min to obtain a clear solution; add pH buffer to the clear solution to adjust it to weak acidity, filter, and obtain nasal wash solution; S2. The nasal rinse solution is metered and filled into an aluminum can, the valve is installed and tightened, and the propellant is filled. According to the weight percentage composition, the nasal rinse solution contains 30-40% and the propellant contains 60-70%. The pressure inside the aluminum can is tested to be within the range of 0.65MPa-0.80MPa. After weighing and water bath testing, a 70° arc-shaped long nozzle and a top cover are installed to obtain a nasal rinse aerosol based on physiological saline.

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