Magnolia flower oil nasal gel and application thereof in treatment of allergic rhinitis
By combining inclusion technology and gel technology, a nasal gel for magnolia flower oil was prepared, which solved the problems of stability and mucosal irritation of magnolia flower oil in the nasal cavity, and achieved effective treatment and safe use for allergic rhinitis.
Patent Information
- Application Number
- CN202511963240.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-24
- Publication Date
- 2026-02-17
AI Technical Summary
Magnolia flower oil has poor stability in the nasal cavity, is highly irritating to the mucous membrane, has low bioavailability, and is difficult to achieve a sustained and effective therapeutic effect.
A nasal gel for magnolia flower oil was prepared by combining inclusion technology and gel technology. By combining the inclusion complex of magnolia flower oil with the gel matrix, the volatility and mucosal irritation of magnolia flower oil are reduced, the adhesion of nasal cavity is enhanced, and the duration of action is prolonged.
It effectively relieves the symptoms of allergic rhinitis, significantly improves patients' nasal and ocular symptom scores and quality of life, is well-tolerated, has a high safety profile, and is suitable for long-term use.
Smart Images
Figure CN121533973A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the field of biological medicine, in particular to a magnolia flower oil nasal gel and its application in treating allergic rhinitis. BACKGROUND
[0002] Magnolia flower oil is a volatile essential oil extracted from the dried flower buds of Magnoliaceae plants such as Magnolia biondii, Magnolia denudata or Magnolia wilsoni, containing terpenes, alcohols, esters and aldehydes and ketones, etc. Compounds, including eucalyptol, farnesol, farnesene, alpha-pinene, beta-pinene, alpha-phellandrene, terpineol, du-son oil, linalool, citral, and terpenes such as eucalyptol, linalool, etc. Alcohols have the effects of dispelling wind and cold, and opening the nasal passages.
[0003] Allergic rhinitis (also known as allergic rhinitis) is mainly mediated by immunoglobulin E (IgE), immune active cells and cytokines, and is a nasal mucosa allergic disease with paroxysmal repeated sneezing, runny nose, and nasal itching as the main symptoms. Allergic rhinitis is divided into perennial and seasonal, and is a common chronic inflammation of the upper respiratory tract, with an incidence of more than 30% in China. At present, allergic rhinitis as a chronic disease has become a global health concern, not only seriously affecting people's quality of life, but also causing a heavy economic burden to society. Therefore, the prevention and treatment of allergic rhinitis is particularly important at this stage. The clinical treatment of allergic rhinitis commonly uses antihistamines, nasal glucocorticoids, leukotrienes and chromone drugs, but only reduces symptoms, requires long-term use, often produces tolerance, and has more adverse reactions. SUMMARY
[0004] The present application discloses a kind of magnolia flower oil nasal gel, and its application in treating allergic rhinitis.The magnolia flower oil nasal gel solves the problems of poor stability of magnolia flower oil, strong nasal mucosa irritation and low bioavailability, and realizes the efficient, safe nasal administration of natural active ingredients.
[0005] The present application combines inclusion technology and gel technology to prepare magnolia flower oil nasal gel, which not only reduces the mucosa irritation of magnolia flower oil and improves the stability, but also enhances the adhesion of the preparation to the nasal mucosa and prolongs the action time, providing a safe and effective natural drug preparation for the treatment of rhinitis.
[0006] Magnolia flower oil nasal gel contains magnolia flower oil, inclusion materials, gelling materials, preservatives, pH adjusters, and water. Preservatives and pH adjusters are not mandatory. Therefore, the formulation of magnolia flower oil nasal gel can be selective. Generally, magnolia flower oil nasal gel contains magnolia flower oil, inclusion materials, gelling materials, and water; magnolia flower oil nasal gel contains magnolia flower oil, inclusion materials, gelling materials, preservatives, and water; magnolia flower oil nasal gel contains magnolia flower oil, inclusion materials, gelling materials, pH adjusters, and water.
[0007] The inclusion material is selected from α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, hydroxypropyl-β-cyclodextrin, sodium sulfobutyl ether-β-cyclodextrin, and preferably β-cyclodextrin, hydroxypropyl-β-cyclodextrin, or sodium sulfobutyl ether-β-cyclodextrin.
[0008] The gel matrix is obtained by adding water to the gel material. The gel material is selected from carbomer 934, carbomer 940, hydroxypropyl methylcellulose K4M, hydroxypropyl methylcellulose K15M, carboxymethyl chitosan, and xanthan gum, preferably from carbomer 934, hydroxypropyl methylcellulose K4M, hydroxypropyl methylcellulose K15M, and carboxymethyl chitosan.
[0009] The preservative is selected from benzalkonium chloride, benzalkonium bromide, methylparaben, ethylparaben, propylparaben, and chlorhexidine, preferably methylparaben and propylparaben.
[0010] pH adjusters are selected from triethanolamine, sodium hydroxide, hydrochloric acid, acetic acid, phosphoric acid and their salts, with triethanolamine, sodium hydroxide and hydrochloric acid being preferred.
[0011] The magnolia flower oil nasal gel contains magnolia flower oil at a content selected from 0.1% to 10%, further selected from 0.2% to 6%, and preferably from 0.5% to 3%.
[0012] The inclusion material content in the Magnolia biondii oil nasal gel is selected from 0.5% to 20%, further selected from 1% to 10%, and preferably from 2% to 5%.
[0013] The gel material content in the Magnolia biondii oil nasal gel is selected from 1% to 30%, further selected from 2% to 20%, and preferably from 5% to 10%.
[0014] The preservative content in the magnolia flower oil nasal gel is selected from 0.01% to 5%, further selected from 0.05% to 3%, and preferably from 0.1% to 2%.
[0015] The preparation of Magnolia biondii flower oil nasal gel involves the following steps:
[0016] (1) Preparation of Magnolia biondii oil inclusion complex using inclusion materials and Magnolia biondii oil;
[0017] (2) Prepare a gel matrix by adding water to a gel material;
[0018] (3) Add the magnolia flower oil inclusion complex to the gel matrix, add water, stir evenly, and obtain magnolia flower oil nasal gel.
[0019] In step (2) above, a preservative or a pH adjuster may be added. When a pH adjuster is selected, the pH value of the prepared composite gel matrix is selected from 6.5 to 8.0, preferably from 7.0 to 7.5.
[0020] The preparation of Magnolia biondii flower oil nasal gel involves the following steps:
[0021] (1) Preparation of Magnolia biondii oil inclusion complex using inclusion materials and Magnolia biondii oil;
[0022] (2) Prepare a gel matrix by adding water to the gel material, add a preservative to dissolve it, and add a pH adjuster to adjust the pH value;
[0023] (3) Add the magnolia flower oil inclusion complex to the composite gel matrix, add water, stir evenly, and obtain magnolia flower oil nasal gel.
[0024] The pH value in step (2) above is selected from 6.5 to 8.0, preferably from 7.0 to 7.5.
[0025] The preparation of the magnolia flower oil inclusion complex follows standard pharmaceutical techniques and can be performed by a person skilled in the art. Generally, the inclusion material is ground together with an appropriate amount of water into a paste, and an appropriate amount of magnolia flower oil is added in portions while stirring. The grinding and stirring are continued to form a suspension of the magnolia flower oil inclusion complex.
[0026] The preparation of the gel matrix follows standard pharmaceutical techniques and can be performed by someone skilled in the art. Generally, the gel material is mixed with an appropriate amount of water and left to stand until it completely swells into a gel.
[0027] Magnolia flower oil, when in its free state, is highly volatile and exhibits extremely poor formulation stability. High concentrations of volatile components, when directly applied to the nasal mucosa, can cause strong irritation, triggering sneezing, burning sensations, and other discomfort. Furthermore, free magnolia flower oil has a short residence time in the nasal cavity and is easily lost through respiration or nasal secretions, resulting in low bioavailability and difficulty in achieving sustained and effective therapeutic effects. Inclusion complexes of magnolia flower oil can reduce oxidative decomposition and volatilization loss, while also minimizing direct irritation to the nasal mucosa, thus improving formulation safety. The gel matrix possesses good biocompatibility, mucosal adhesion, and moisturizing properties, prolonging the residence time of the formulation on the nasal mucosa and promoting sustained absorption of active ingredients. Combining inclusion and gel technologies to prepare a nasal gel for magnolia flower oil can reduce its volatility and mucosal irritation, improve its stability, enhance the adhesion of the formulation to the nasal mucosa, and prolong the duration of action.
[0028] The Magnolia biondii oil nasal gel of this invention is used to treat allergic rhinitis and can effectively relieve clinical symptoms such as nasal congestion, nasal itching, runny nose, and sneezing. When using, first clean the nasal cavity, keep the head tilted back, and drip the gel into each nostril, keeping the head tilted back for 10 seconds, avoiding blowing the nose immediately.
[0029] The Magnolia biondii oil nasal gel of the present invention has the following outstanding advantages for treating allergic rhinitis: (1) Low mucosal irritation: The Magnolia biondii oil inclusion complex in the Magnolia biondii oil nasal gel reduces the local concentration of Magnolia biondii oil on the nasal mucosa surface, and the moisturizing and soothing effect of the gel further reduces irritation. Clinical studies show that only a very small number of patients with allergic rhinitis experience mild discomfort when using the Magnolia biondii oil nasal gel, and the tolerance is good; (2) Definite clinical efficacy: A randomized, double-blind, placebo-controlled trial of the Magnolia biondii oil nasal gel for the treatment of allergic rhinitis has confirmed that after 14 days of continuous use of the Magnolia biondii oil nasal gel, it can reduce the local concentration of Magnolia biondii oil on the nasal mucosa surface. It significantly improved the TNSS score, VAS score and quality of life score of patients with allergic rhinitis, and the treatment effect was obvious. The total effective rate was 63.41%, which was significantly higher than the effective rate of 29.27% in the placebo group and there was a statistical difference. (3) The preparation process is simple: the preparation process of Magnolia flower oil nasal gel is highly controllable and easy to operate, and is suitable for industrial-scale production. (4) It has good safety: the incidence of adverse events in the clinical study of Magnolia flower oil nasal gel for the treatment of allergic rhinitis was low and basically unrelated to the drug. There were no reports of serious adverse reactions, and it is suitable for long-term use by patients with allergic rhinitis. Attached Figure Description
[0030] Figure 1 Photo of the appearance of Magnolia Flower Oil Nasal Gel Detailed Implementation
[0031] Example 1. Magnolia flower oil nasal gel
[0032] Take 12.5g of carboxymethyl chitosan and 3g of propylparaben, add 250mL of water, stir magnetically for 10min to mix, and let stand at room temperature overnight to swell, ensuring that the carboxymethyl chitosan is completely dissolved, to obtain a uniform 5% carboxymethyl chitosan solution; take 12.5g of carbomer 934, add 1250mL of water, stir overnight to allow it to swell fully, to form a carbomer solution; take 90g of β-cyclodextrin, add 100mL of water and grind to a paste, while stirring at high speed and adding 12mL of magnolia flower oil in portions, continuing to grind and stir for 40min to form a uniform and stable magnolia flower oil inclusion complex suspension; slowly add the carboxymethyl chitosan solution to the carbomer solution, stirring until mixed evenly, and adjust the pH to 7.5 dropwise with sodium hydroxide solution, while continuing to stir; slowly add the magnolia flower oil inclusion complex suspension to the above composite gel matrix, add 900mL of water, and continue stirring for 30min to obtain magnolia flower oil nasal gel.
[0033] The nasal gel system of Magnolia biondii oil is uniform, without particles or stratification, and appears as a slightly white, uniform suspension.
[0034] Example 2. Magnolia flower oil nasal gel
[0035] Take 12.5g of carboxymethyl chitosan and 3.0g of methylparaben, add 250mL of water, and stir magnetically for 10 minutes. n Mix well and allow to stand at room temperature overnight to swell, ensuring complete dissolution of carboxymethyl chitosan, to obtain a uniform 5% carboxymethyl chitosan solution; take 12.5g of carbomer 934, add 1250mL of water, stir overnight to allow it to swell fully, forming a carbomer solution; take 120g of hydroxypropyl-β-cyclodextrin, add 100mL of water and grind until a paste is formed, while stirring at high speed and adding 12mL of magnolia flower oil in portions, continuing to grind and stir for 40min to form a uniform and stable magnolia flower oil inclusion complex suspension; slowly add the carboxymethyl chitosan solution to the carbomer solution, stirring until evenly mixed, and adjust the pH to 7.0 dropwise with triethanolamine, continuing to stir; slowly add the magnolia flower oil inclusion complex suspension to the above composite gel matrix, add 900mL of water, and continue stirring for 30min to obtain magnolia flower oil nasal gel.
[0036] The nasal gel system of Magnolia biondii oil is uniform, without particles or layering, and has a uniform and transparent appearance.
[0037] Example 3. Magnolia flower oil nasal gel
[0038] Take 12.5g of carboxymethyl chitosan and 3.0g of methylparaben, add 250mL of water, stir magnetically for 10min to mix, and let stand at room temperature overnight to swell, ensuring that the carboxymethyl chitosan is completely dissolved, to obtain a uniform 5% carboxymethyl chitosan solution; take 12.5g of carbomer 934, add 1250mL of water, stir overnight to allow it to swell fully, to form a carbomer solution; take 75g of sodium sulfobutyl ether-β-cyclodextrin, add 75mL of water and grind to a paste, while stirring, add 12mL of magnolia flower essential oil in portions, continue grinding and stirring for 30min to form a magnolia flower oil inclusion complex suspension; slowly add the carboxymethyl chitosan solution to the carbomer solution, stir until mixed evenly, adjust the pH to 7.5 dropwise with triethanolamine, and continue stirring during this process; slowly add the magnolia flower oil inclusion complex suspension to the above composite gel matrix, add 900mL of water, and continue stirring for 30min to obtain a magnolia flower oil nasal gel.
[0039] The magnolia flower oil nasal gel system is homogeneous, without particles or layering, and has a uniform and transparent appearance. Figure 1 ).
[0040] Experimental Example: Clinical efficacy and safety evaluation of Magnolia flower oil nasal gel.
[0041] Materials: Magnolia flower oil nasal gel prepared according to Example 3, and blank gel prepared according to Example 3 (without Magnolia flower oil, but with the same other components).
[0042] method:
[0043] Treatment plan: The inclusion criteria for clinical study participants were: ① experiencing two or more symptoms such as paroxysmal sneezing, clear nasal discharge, nasal itching, and nasal congestion, with symptoms lasting or accumulating for more than 1 hour per day (without significant impact on quality of life, including sleep, daily life, work, and study); ② physical signs including pale and swollen nasal mucosa, edema of the inferior turbinate, and watery nasal discharge; ③ age 18–85 years; ④ willingness to participate in this study and ability to cooperate in completing the follow-up work of this study, and ability to understand and sign the informed consent form.
[0044] Exclusion criteria: ① Not meeting the above inclusion criteria; ② Known history of allergy to the investigational drug or any of its related components; ③ Participation in other clinical trials within the past month; ④ Patients with sinusitis, drug-induced rhinitis, or nasal polyps; ⑤ Patients with serious primary diseases of the cardiovascular, cerebrovascular, liver, kidney, or hematopoietic systems.
[0045] Patients with allergic rhinitis were divided into a control group and an experimental group. One group received hydrogel / magnolia flower oil nasal gel treatment. The clinical efficacy of the magnolia flower oil nasal gel in treating allergic rhinitis was analyzed. The experimental group used the magnolia flower oil nasal gel. The gel should be shaken well before use. Apply 1-2 drops to each nostril 3-8 times daily for 14 consecutive days. The placebo group received a blank gel with the same dosage and administration method.
[0046] Observation indicators:
[0047] (1) Main efficacy indicators: Nasal and ocular symptom scores: Scores were taken before treatment and on day 14 after treatment. The total nasal symptom score (TNSS) of the four rhinitis symptoms, as well as individual symptoms including sneezing, runny nose, nasal itching, and nasal congestion, were scored. At the same time, the total ocular symptom score (TOSS) of the patients: itchy eyes, red eyes, and tearing were quantitatively scored. The severity was evaluated on a scale of 0 to 3. The scores were added together to calculate the total TNSS score. The higher the score, the more severe the symptoms. The total score of the scale was 12 points.
[0048] (2) Secondary efficacy indicators: ① Quality of life score: Scores were taken before treatment and on day 14 after treatment using the Rhino conjunctivitis Quality of life Questionnaire (RQLQ). The RQLQ covers 28 questions across 7 dimensions: activity, sleep, non-nasal / ocular symptoms, practical problems, nasal symptoms, ocular symptoms, and emotional state. Each question was scored from 0 to 6 points, with higher scores indicating poorer quality of life. The total score was 168 points. ② VAS score: The VAS score scale was divided into 10 points, with 0 representing no symptoms and 10 representing the most severe symptoms. The progression from 0 to 10 indicated a gradual increase in the severity of AR.
[0049] (3) Safety indicators: Record adverse reactions during medication, including symptoms such as cough, headache, dizziness, and palpitations.
[0050] Efficacy evaluation criteria: Efficacy index = (Total score of nasal and ocular symptoms before treatment - Total score of nasal and ocular symptoms after treatment) / Total score of nasal and ocular symptoms before treatment × 100%. An efficacy index ≥ 66% is considered significantly effective, 26%–65% is considered effective, and ≤ 25% is considered ineffective. The overall effective rate is calculated based on the number of cases with significant and effective results.
[0051] result:
[0052] Intergroup comparisons of primary and secondary efficacy endpoints: On day 14 post-treatment, the Magnolia biondii oil nasal gel group showed significantly greater improvement in the primary efficacy endpoint TNSS total score than the placebo group (change: -2.59±2.67 vs. -0.95±2.62, P=0.006). Regarding secondary efficacy endpoints, the experimental group also showed significantly greater improvement than the placebo group in VAS score (-2.15±1.97 vs. -0.98±2.06, P=0.010), TOSS total score (-1.76±1.77 vs. -0.73±2.44, P=0.033), and RQLQ quality of life score (-24.41±23.13 vs. -11.71±22.14, P=0.013), with statistically significant differences (Table 1).
[0053] Changes in symptom scores after two weeks of treatment: After two weeks of treatment, both groups showed significant improvements in total TNSS score, scores for various nasal and ocular symptoms, and RQLQ score compared to baseline (P<0.05). Further intergroup comparisons showed that the Magnolia biondii oil nasal gel group showed significantly better improvement than the placebo group in total TNSS score, VAS score, RQLQ score, and multiple nasal symptoms (runny nose, sneezing) and ocular symptoms (red eyes) (P<0.05), suggesting that this treatment regimen has a significant advantage in comprehensively relieving nasal and ocular symptoms and improving quality of life (Table 2).
[0054] Comparison of efficacy evaluation between the two groups: According to the efficacy evaluation criteria, the total effective rate of the Magnolia Flower Oil Nasal Gel group was 63.41%, significantly higher than that of the placebo group (29.27%), and the difference between the groups was highly statistically significant (P<0.01). Specifically, the markedly effective rate and the effective rate of the experimental group were 21.95% and 41.46%, respectively, both higher than those of the placebo group (14.63% and 14.63%), further confirming the clinical efficacy of the Magnolia Flower Oil Nasal Gel (Table 3).
[0055] Table 1. Intergroup comparisons of primary and secondary efficacy endpoints
[0056]
[0057] Table 2. Changes in symptom scores after two weeks of treatment
[0058]
[0059] Note: ΔP<0.05 compared with baseline in the same group; ΔP<0.01 compared with baseline in the same group; *P<0.05 compared with placebo group at the same time point; **P<0.01 compared with placebo group at the same time point.
[0060] Table 3. Comparison of efficacy evaluation between the two groups of patients.
[0061]
[0062] Note: **P < 0.01 compared to the placebo group.
[0063] Safety and Adverse Events: In the placebo group, 4 adverse events occurred, 3 of which were deemed "probably related": 2 cases of mild nasal bleeding lasting 2 days; 1 case of moderate nasal bleeding lasting 9 days; and 1 case of "definitely unrelated" (upper respiratory tract infection). In the experimental group, 2 adverse events were reported, 2 of which were "definitely unrelated": 1 case of mild arousal lasting 8 days; and 1 case of acute depressive episode. One patient from each group withdrew from the study due to adverse events. All adverse events were treated symptomatically or resolved spontaneously, and did not have a significant impact on the overall safety of the study (Table 4). The incidence of adverse events in the experimental group was 4.88%, all of which were non-drug-related; the incidence of adverse events in the placebo group was 9.76%, with no serious adverse events. The safety profile of both groups was good.
[0064] The above results confirm that the Magnolia biondii oil nasal gel of the present invention is effective and safe in treating allergic rhinitis.
[0065] Table 4. Summary of Adverse Events
[0066]
[0067] Note: **P < 0.01 compared to the placebo group.
Claims
1. A nasal gel containing magnolia flower oil, characterized in that... Used to treat allergic rhinitis.
2. The magnolia flower oil nasal gel as described in claim 1, comprising magnolia flower oil, inclusion material, gel material, preservative, pH adjuster, and water.
3. The magnolia flower oil nasal gel as described in claim 1, comprising magnolia flower oil, inclusion material, gel material, and water.
4. The magnolia flower oil nasal gel as described in claim 1, comprising magnolia flower oil, inclusion material, gel material, preservative, and water.
5. The magnolia flower oil nasal gel as described in claim 1, comprising magnolia flower oil, inclusion material, gel material, pH adjuster, and water.
6. The Magnolia biondii oil nasal gel according to claims 2 to 5, wherein the inclusion material is selected from α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, hydroxypropyl-β-cyclodextrin, and sodium sulfobutyl ether-β-cyclodextrin.
7. The Magnolia biondii oil nasal gel as described in claims 2 to 5, wherein the gel material is selected from carbomer 934, carbomer 940, hydroxypropyl methylcellulose K4M, hydroxypropyl methylcellulose K15M, carboxymethyl chitosan, and xanthan gum.
8. The Magnolia biondii oil nasal gel according to claims 2 and 4, wherein the preservative is selected from benzalkonium chloride, benzalkonium bromide, methylparaben, ethylparaben, propylparaben, and chlorhexidine.
9. The Magnolia biondii oil nasal gel according to claims 2 and 5, wherein the pH adjuster is selected from triethanolamine, sodium hydroxide, hydrochloric acid, acetic acid, phosphate and their salts.
10. The nasal gel for magnolia flower oil as described in claims 1 and 2, prepared by the following steps: (1) Preparation of Magnolia biondii oil inclusion complex using inclusion materials and Magnolia biondii oil; (2) Prepare a gel matrix by adding water to the gel material, add a preservative to dissolve it, and add a pH adjuster to adjust the pH value; (3) Add the magnolia flower oil inclusion complex to the composite gel matrix, add water, stir evenly, and obtain magnolia flower oil nasal gel.