Composition for nasal spray and preparation method therefor

Abstract

The present disclosure relates to a composition for a nasal spray and a preparation method therefor, wherein the composition comprises camostat mesylate as an active ingredient in addition to xanthan gum, thereby having improved mucosal adhesion and film-forming performance.

Description

Composition for nasal spray and method for preparing the same

[0001] The present invention relates to a composition for nasal spray and a method for producing the same.

[0002] With the recent COVID-19 pandemic and growing concerns about air pollution, including fine dust and yellow dust, interest in nasal health, the front line of immunity, is on the rise. Consequently, demand is growing for products that can be sprayed onto the nasal mucosa to protect it from bacteria and viruses that invade the nose.

[0003] Meanwhile, the nasal cavity is the first to be exposed to external substances, as it can detect even extremely low concentrations of odors, and is a very sensitive organ with many nerves distributed so that it can react sensitively to even the smallest amount of external toxic substances. Therefore, products that do not cause irritation but can prevent the entry of bacteria and viruses are needed. Currently, there are nasal sprays on the market such as Koan nasal spray containing dexpanthenol and sodium hyaluronate, Maprus nasal spray containing sterile natural seawater and dexpanthenol, and Bizain nasal spray containing despanthenol. Koan and Maprus nasal sprays had poor adhesion, so their efficacy lasted for a short time, and Bizain nasal spray contained benzalkonium chloride, which can cause bronchial spasm, and there were problems in that it could cause irritation or swelling in the nasal cavity, and swelling of the nasal mucosa with long-term use.

[0004] The purpose of the present invention is to solve the above-described problems, and to provide a composition for nasal spray that is harmless to the human body and has improved mucosal adhesion and film-forming performance compared to existing compositions, and a method for manufacturing the same.

[0005] To achieve the above purpose, a composition for nasal spray according to one embodiment of the present invention comprises xanthan gum and camostat mesylate as active ingredients.

[0006] According to another embodiment of the present invention, a method for manufacturing a composition for nasal spray comprises the steps of (a) sterilizing a solvent by heating, (b) cooling the sterilized solvent to 45 to 55°C and then adding a fragrance and a preservative and mixing them for the first time, (c) adding an isotonic agent to the first mixed mixture and mixing them for the second time, (d) cooling the second mixed mixture to 20 to 30°C and then adding camostat mesylate and mixing them for the third time, (e) adding a pH adjuster to the third mixed mixture and adjusting the pH to 3 to 5, (f) mixing xanthan gum into the pH-adjusted solution and then adding a sterilized solvent, and (g) filtering the mixture to which the sterilized solvent has been added.

[0007] According to one embodiment of the present invention, a composition for nasal spray and a method for manufacturing the same can improve mucosal adhesiveness and film-forming performance by including camostat mesylate as an active ingredient in addition to xanthan gum.

[0008] Additionally, it is harmless to the human body as it does not contain substances that irritate the nasal cavity, while protecting the nasal mucosa.

[0009] Figure 1 is a diagram showing the hydrogen bonding and ionic bonding structures of xanthan gum and camostat mesylate.

[0010] Figure 2 is a process diagram illustrating a method for manufacturing a composition for nasal spray according to another embodiment of the present invention.

[0011] Figure 3 is a photograph showing the initial (0 hr) drying pattern in Experimental Example 1-1.

[0012] Figure 4 is a photograph showing the drying pattern in the middle stage (3.5 hr) of Experimental Example 1-1.

[0013] Figure 5 is a photograph showing the drying state at the end (5 hours) in Experimental Example 1-1.

[0014] Figure 6 is a photograph showing the appearance immediately after application (0 hr) in Experimental Example 1-2.

[0015] Figure 7 is a photograph showing the appearance after drying (3 hours) in Experimental Example 1-2.

[0016] Figure 8 is a graph showing the results according to Experimental Example 2.

[0017] Figure 9 is a graph showing the analysis results by the flow sweep measurement method of Experimental Example 3-1.

[0018] Figures 10 and 11 are graphs showing the analysis results by the step flow measurement method of Experimental Example 3-2.

[0019] Figures 12 to 14 are graphs showing the analysis results by the oscillation frequency sweep measurement method of Experimental Example 3-3.

[0020] Hereinafter, the present invention will be described in detail with reference to the attached drawings, using exemplary embodiments. However, the following exemplary embodiments are provided as illustrative examples of the present invention. If a detailed description of a technology or configuration well known to those skilled in the art is judged to unnecessarily obscure the gist of the present invention, such detailed description may be omitted, and the present invention is not limited thereby. The present invention is capable of various modifications and applications within the scope of the following claims and equivalents interpreted therefrom.

[0021] In addition, the terms used in this specification are terms used to appropriately express preferred embodiments of the present invention, and may vary depending on the intention of the user or operator, or the customs of the field to which the present invention belongs. Therefore, the definitions of these terms should be determined based on the contents throughout this specification. Throughout the specification, when a part is said to "include" a certain component, this does not mean that other components are excluded, but rather that other components may be included, unless specifically stated otherwise.

[0022] Throughout this specification, '%' used to indicate the concentration of a particular substance is %(w / w) for solid / solid, %(w / v) for solid / liquid, and %(v / v) for liquid / liquid, unless otherwise stated.

[0023]

[0024] Hereinafter, a composition for nasal spray according to one embodiment of the present invention will be described in detail.

[0025] The composition for nasal spray according to the present embodiment is a type of adhesive transparent wound dressing used to prevent the penetration of respiratory infection viruses and protect the mucosa by forming a physical film on the nasal mucosa by spraying it into the nasal cavity. It is preferable that the composition for nasal spray has a viscosity change amount after spraying and application that is equal to or greater than a predetermined value so that it can be attached into the nasal cavity and form a film over a relatively wide area. For example, it is preferable that the viscosity change amount is equal to or greater than 4 cp. For example, as a result of a rotational rheometer (RHEOMETER(AR)) instrument analysis using a 60 mm cone plate, 10 3 ~10 5 The difference between the viscosity measured under shear rate (1 / s) conditions and the viscosity measured under 1 shear rate (1 / s) conditions may be more than 4 cp. For example, according to the analysis results of a rotational rheometer (RHEOMETER (AR)) using a 40 mm cone plate, 10 3 ~10 5 When changing from a Shear rate(1 / s) condition to a 1 Shear rate(1 / s) condition, the measured viscosity may be 4cp or more.

[0026] The composition for nasal spray comprises xanthan gum and camostat mesylate as active ingredients.

[0027] Xanthan gum has an ordered and rigid double helix strand structure, and the xanthan gum chains form a three-dimensional network, exhibiting gel-like properties and can be cross-linked to form a hydrogel. Cross-linking includes hydrogen bonds, ionic bonds, ππ stacking, hydrophobic interactions, and host-guest inclusions. As shown in Figure 1, the structure of xanthan gum is a polymer structure with many -OH groups. When in an aqueous solution, the -OH groups of xanthan gum form strong hydrogen bonds with water molecules, which reduces the fluidity of water molecules and can increase viscosity. In addition, xanthan gum can form a physical network with cations and form intramolecular cross-links. Such xanthan gum may be included in an amount of 0.01 to 0.04 wt%, preferably 0.02 to 0.03 wt%, based on the total weight of the composition. However, if the amount of xanthan gum is less than 0.01 wt%, the amount of hydrogel is insufficient, and if it exceeds 0.04 wt%, the viscosity may increase unnecessarily, which is not preferable.

[0028] Camostat mesylate plays a role in strengthening the membrane-forming performance of xanthan gum. As shown in Figure 1, there can be many N, O, and H atoms that can form hydrogen bonds with xanthan gum, with Hydrogen bond donor=2 / Hydrogen bond Acceptor=6 / Rotatable bond=9. In addition to hydrogen bonding, positively charged camostat mesylate can also strengthen the membrane (gel) network through ionic bonding with negatively charged xanthan gum in a solution state. For example, the pKa of xanthan gum is 3.1, the pKa of camostat mesylate is 19.54 in the acidic phase, and 8.54 in the basic phase. Camostat mesylate and xanthan gum form two types of bonds (hydrogen and ionic bonds) in the liquid phase, exhibiting ionic properties, strong electrical interactions, and allowing ions to move freely. Such camostat mesylate may be included in an amount of 0.02 to 0.10 wt%, preferably 0.03 to 0.04 wt%, based on the total weight of the composition. If camostat mesylate is included in an amount of less than 0.02 wt%, it may be difficult to form a sufficient film on the hydrogel, and if it exceeds 0.10 wt%, the effect due to excessive use may not be that great.

[0029] For example, camostat mesylate can further strengthen cross-linking with xanthan gum through hydrogen bonding and ionic bonding, and the main effect, xanthan gum, forms a physical hydrogel in the nasal mucosa, and the auxiliary effect, camostat mesylate, can strengthen membrane (gel) formation.

[0030] Meanwhile, the composition for nasal spray may further include one or more selected from a preservative, an isotonic agent, a fragrance, a pH regulator, and a solvent in addition to xanthan gum and camostat mesylate.

[0031] Preservatives are substances added to suppress changes in microbial growth, and may be one or more selected from benzoic acid, benzalkonium chloride, phenyl ethyl alcohol, phenoxyethanol, and benzyl alcohol, preferably benzoic acid. These preservatives may be included in an amount of 0.05 to 0.07 wt% based on the total weight of the composition. If the preservative amount is less than 0.05 wt%, the antibacterial activity may be reduced, shortening the shelf life. If the preservative amount exceeds 0.07 wt%, the pH may decrease, causing irritation to the nasal mucosa.

[0032] Tonicity agents are substances added to improve the solubility of other ingredients and increase adhesion to the nasal mucosa. D-sorbitol can be used. This tonicity agent can be included in an amount of 2 to 5 wt% based on the total weight of the composition. However, if the tonicity agent is included in an amount of less than 2 wt%, it may be difficult to maintain the appropriate viscosity required for the spray formulation, and if it exceeds 5 wt%, the osmotic pressure may increase.

[0033] A fragrance is a substance added to improve the user preference by allowing the user to sense a fragrance when spraying, and at least one selected from L-menthol, DL-camphor, eucalyptol, and peppermint oil, preferably L-menthol, can be used. Such a fragrance may be included in an amount of 0.01 to 0.03 wt% based on the total weight of the composition. If the fragrance is less than 0.01 wt%, the effect of masking each unique fragrance of the composition may be minimal, and if it exceeds 0.03 wt%, it may have a negative effect on physiological changes due to stimulation of the olfactory sense by the fragrance.

[0034] A pH adjuster is a substance added to improve the user experience by alleviating irritation, such as a stinging sensation, of the nasal mucosa when sprayed into the nasal cavity. Sodium hydroxide can be used. An appropriate amount of this pH adjuster can be added within a range that satisfies the pH requirement of 3 to 5, and is preferably included at 0.001 to 0.05 wt% of the total weight of the composition. When the above-mentioned range is met, optimal antibacterial activity and an extended shelf life are achieved, while alleviating irritation of the nasal mucosa when sprayed into the nasal cavity.

[0035] The solvent is a liquid medium, and at least one of purified water and ethanol can be used, preferably purified water. The solvent may be included in an amount of 95 to 97 wt% based on the total weight of the composition. If the solvent is less than 95 wt%, the appropriate viscosity required for the spray formulation is not secured, resulting in a small spray amount and difficulty for the composition to reach the nasal mucosa, which may result in a slight decrease in efficacy. If the solvent is more than 97 wt%, it may not adhere to the nasal mucosa and may easily flow outward.

[0036]

[0037] Hereinafter, a method for manufacturing a composition for nasal spray according to another embodiment of the present invention will be described in detail with reference to the drawings. Since each component has been described in detail above, any redundant description will be omitted.

[0038] Figure 2 is a process diagram illustrating a method for manufacturing a composition for nasal spray according to another embodiment of the present invention.

[0039] Referring to Figure 2, first, the solvent is heated and sterilized (S10).

[0040] Sterilization can be achieved by heating the solvent to 80-100°C. Sterilization is preferably performed at 200-600 rpm for 20-40 minutes. If the temperature and time are exceeded, microorganisms present in the solvent can easily multiply.

[0041]

[0042] Then, the sterilized solvent is cooled to 45-55℃, and then fragrance and preservatives are added and mixed for the first time (S20).

[0043] In the above step S10, the sterilized solvent is cooled to 45-55°C, and then a fragrance and preservative are added. The initial mixing can be performed at 200-600 rpm for 30-90 minutes. If the temperature range mentioned above is exceeded, the fragrance may evaporate, so it is advisable to check the temperature before adding the fragrance. If the mixing time mentioned above is exceeded, it may be difficult for the fragrance and preservative to be evenly mixed within the composition.

[0044]

[0045] After that, a topical agent is added to the first mixed mixture and mixed a second time (S30).

[0046] In the above S20 step, an isotonic agent can be added to the first mixed mixture and mixed a second time at 200 to 600 rpm for 10 to 60 minutes.

[0047]

[0048] Next, the second mixed mixture is cooled to 20-30°C, and camostat mesylate is added and mixed for the third time (S40).

[0049] After the second mixed mixture in the above S30 step is cooled to 20 to 30°C, camostat mesylate can be added and mixed a third time at 200 to 600 rpm for 10 to 60 minutes.

[0050]

[0051] Then, add a pH adjuster to the third mixed mixture and adjust the pH to 3-5 (S50).

[0052] In the above S40 step, the pH can be adjusted to 3 to 5 by adding a pH adjuster to the third mixed mixture, and it is also acceptable to do so while stirring at 200 to 300 rpm for 10 to 60 minutes.

[0053]

[0054] After that, xanthan gum is mixed into the pH-adjusted solution and a sterilized solvent is added (S60).

[0055] In the above S50 step, the xanthan gum is slowly added to the pH-adjusted solution to prevent it from clumping with the raw material, and the solution is dissolved at 200 to 600 rpm for 90 to 150 minutes, after which the sterilized solvent can be added. Since xanthan gum easily clumps with the raw material and does not mix well, it is preferable to mix for a longer time than the mixing time in the first to third mixing mentioned above.

[0056]

[0057] Finally, the mixture with the sterilized solvent added is filtered (S70).

[0058] The mixture to which the sterilized solvent has been added in the above step S60 can be filtered using a 5-10㎛ filter.

[0059]

[0060] Hereinafter, the present invention will be described in more detail using examples. These examples are intended solely to illustrate the present invention more specifically, and it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples.

[0061]

[0062] Example 1. Preparation of a composition for nasal spray

[0063] After sterilizing 150 kg of purified water by heating to 90℃, only 30 kg of purified water was cooled to 50℃, and 0.030 kg of L-menthol and 0.090 kg of benzoic acid were added and mixed at 500 rpm for 1 hour while maintaining the temperature at 50℃. Then, 5.250 kg of D-sorbitol solution was added and mixed at 500 rpm for 1 hour while maintaining the temperature at 50℃. Then, after cooling to 25℃, 0.0525 kg (0.035 wt% (0.35 mg / mL)) of camostat mesylate was added and mixed at 500 rpm for 1 hour, and sodium hydroxide was added and mixed for 20 minutes to adjust the pH to 4. 0.0375 kg of xanthan gum was dissolved here at 500 rpm for 1 hour, the remaining purified water was added, mixed, and filtered through a 5-10 μm filter.

[0064]

[0065] Examples 2 to 5. Preparation of composition for nasal spray

[0066] A composition for nasal spray was prepared in the same manner as in Example 1, except that camostat mesylate was applied in the proportions described in Table 1 below.

[0067] Classification Camostat mesylate content (weight %) Example 20.02 (0.2 mg / mL) Example 30.07 (0.7 mg / mL) Example 40.10 (1.0 mg / mL)

[0068]

[0069] Comparative Example 1. Preparation of a composition for nasal spray

[0070] A nasal spray was prepared in the same manner as in Example 1, except that camostat mesylate was not used.

[0071]

[0072] Experimental Example 1: Evaluation of Drying Pattern

[0073] 1-1. Drying pattern test according to the presence or absence of camostat mesylate

[0074] The composition for nasal spray according to Example 1 and Comparative Example 1 was applied in an amount of 1 ml to each 3.5 cm diameter plate and then dried in a dry oven at 60°C. The drying pattern was checked at the initial (0 hr), middle (3.5 hr), and final (5 hr) stages, and the results are shown in Figures 3 to 5.

[0075] The experimental group on the left was applied to the plate considering surface tension, and the experimental group on the right was applied with physical vibration to attach it to the plate as much as possible and then dried.

[0076] Referring to Fig. 3, in the initial stage, Comparative Example 1 had a strong surface tension and did not attempt to attach to the plate but rather clumped together, and it was confirmed that there was no significant difference from Example 1. Referring to Fig. 4, in the middle stage, Comparative Example 1 was attached to the surface and existed in a liquid state that was not dried, whereas Example 1 was attached to a relatively wide area and dried. Referring to Fig. 5, in the final stage, Comparative Example 1 was dried as is at the applied location, whereas Example 1 was attached to a wide area and dried. As a result, it was found that the difference in area depending on the presence or absence of camostat mesylate was about 4 times on the left side and about 10.3 times on the right side.

[0077]

[0078] 1-2. Drying pattern test according to the content of camostat mesylate

[0079] The compositions for nasal spray according to Examples 1 to 4 were applied in an amount of 1 ml to a 3.5 cm diameter plate while physically vibrating, and then dried in a dry oven at 37°C. The appearance immediately after application (0 hr) and after drying (3.0 hr) was confirmed, and the results are shown in Figs. 6 and 7.

[0080] Referring to FIGS. 6 and 7, it was confirmed that immediately after application (0 hr), camostat mesylate was applied and adhered to the entire plate surface regardless of the content. After drying (3 hr), although there were some differences (white arrows) in the drying areas of Examples 1 and 2 with low contents of camostat mesylate, it was confirmed that a film was formed and that the camostat mesylate was attached and dried over a relatively wide area at all contents. In particular, it was confirmed that Examples 3 and 4 with high contents of camostat mesylate were attached and dried over a relatively wide area compared to Examples 1 and 2.

[0081]

[0082] Experimental Example 2: Viscosity Evaluation According to the Content of Camostat Mesylate

[0083] In order to determine the physical properties according to the content of camostat mesylate, the viscosity of Examples 1 to 4 was measured using a BrookField viscometer, and the results are shown in Fig. 8.

[0084] The BrookField viscometer was set to zero point and the rotation speed was 1.0 RPM to measure the viscosity of the sample. The sample was approximately 20 mL and the rotation speed was 1.0 RPM, which is 1.223 s when converted to shear rate. -1 can have the speed of .

[0085] Referring to Figure 8, as the content of camostat mesylate increased, the viscosity tended to increase, and the viscosity was highest in the order of Example 4 (9.00cp), Example 3 (8.40cp), Example 1 (7.80cp), and Example 2 (7.20cp).

[0086]

[0087] Experimental Example 3: Evaluation of Viscoelastic Behavior

[0088] Viscosity and viscoelasticity were measured sequentially using a rotational rheometer (RHEOMETER(AR)) according to the following measurement methods: (1) flow sweep, (2) step flow, and (3) oscillation frequency sweep. To clearly confirm the experimental values, the measurements using a 60 mm cone plate and a 40 mm cone plate were distinguished.

[0089]

[0090] 3-1. Flow sweep: Evaluation of the relationship between shear rate and viscosity

[0091] Using a 60 mm cone plate, the shear rate was sequentially changed while a certain rest time was passed, and the flow curve data was measured, and the results are shown in Fig. 9.

[0092] Referring to Figure 9, when the shear rate was low (white arrow), the viscosity difference between Comparative Example 1 and Example 1 was large, but it was confirmed that the viscosity difference decreased as the shear rate increased (black arrow). As a result, it was confirmed that Example 1 had a greater viscosity decrease than Comparative Example 1, indicating that Example 1 has molecules that are better oriented than Comparative Example 1.

[0093]

[0094] 3-2. Step flow: Viscosity evaluation after spraying and application

[0095] Step Flow is a method of measuring the viscosity of a sample by simulating a specific process intended for each phase by setting the shear rate, which determines the rotation speed of the rheometer, step by step. The phases were set by maintaining the shear rate at a high speed and then changing it to a low speed, and the physical properties were compared by assuming the situation after spray injection and application.

[0096] The spray injection situation is 103 ~10 5 The shear rate (1 / s) condition was set, and the stationary situation, i.e., the application water situation, was set to 1 Shear rate (1 / s) condition. Based on this, approximately 1 to 2 mL of sample was dispensed into the device and then 1000 s -1 1s in (Phase1) -1 (Phase2) was changed and the average viscosity for each phase was measured. The results using a 60 mm Cone plate are shown in Fig. 10, and the results using a 40 mm Cone plate are shown in Fig. 11.

[0097] Referring to FIG. 10, under spray injection conditions, the viscosity of Example 1 was 1.57 cP and that of Comparative Example 1 was 1.51 cP, which were similar, but after application, the viscosity of Example 1 was 7.69 cP and that of Comparative Example 1 was 5.18 cP, which were relatively large differences. As a result, it was confirmed that the viscosity increase of Example 1 was higher than that of Comparative Example 1, and specifically, while the viscosity change after spray injection and application in Example 1 was 6.12 cP, it was confirmed that it was 3.66 cP in Comparative Example 1. In other words, it was found that Example 1 and Comparative Example 1 had a viscosity difference of about 1.7 times. That is, as a result of the analysis using a rotational rheometer (RHEOMETER(AR)) using a 60 mm cone plate, the composition for nasal spray according to the present invention, 10 3 ~10 5 The difference between the viscosity measured under shear rate (1 / s) conditions and the viscosity measured under 1 shear rate (1 / s) conditions was more than 4 cp, confirming that the viscosity increased significantly after application.

[0098] Referring to Fig. 11, under spray injection conditions, the viscosity was all 2 cp or less regardless of the content of camostat mesylate (black arrow), but after application, the viscosity of Example 1 containing 0.35 wt% of camostat mesylate was the highest at 31.49 cp. In addition, the viscosity was highest in the order of Example 4 (9.43 cp), Example 2 (4.96 cp), and Example 3 (4.86 cp). That is, as a result of the rotational rheometer (RHEOMETER(AR)) instrument analysis using a 40 mm cone plate, the composition for nasal spray according to the present invention, 3 ~10 5 When the shear rate (1 / s) condition was changed to 1 shear rate (1 / s), the measured viscosity was 4 cp or more, and it was confirmed that the viscosity after application increased significantly in all examples.

[0099]

[0100] 3-3. Oscillation frequency sweep: Viscoelasticity evaluation

[0101] Oscillation Frequency Sweep is a measurement method to evaluate the viscoelasticity of a sample while changing the angular frequency. In order to confirm the physical properties of the sample by assuming the environment after application, the viscoelasticity evaluation according to the frequency of the sample was performed. Except for the situation immediately after spraying, where the degree of oscillation is severe, the values ​​were compared at a relatively low oscillation of angular frequency 100 or less, which is the situation after spraying. In order to clearly confirm the experimental values, the experimental values ​​using a 60 mm cone plate are shown in Fig. 12, and the experimental values ​​using a 40 mm cone plate are shown in Figs. 13 and 14.

[0102] Spray injection is 10 0 and 10 1The middle section (white arrow) is the section indicated by the black dotted arrow after application. Storage modulus (G') is the elastic coefficient, which is a numerical value (blue) indicating how much it changes in response to an external force (Stress). In other words, it is the storage modulus, which means the elasticity that the sample has inherently. In general, a high G' can mean that the force to return to its original state is large. Complex viscosity (η) is the numerical value (red) for the resistance as a complex viscosity, and Tan delta (Tan delta = G' / G'') is the loss tangent, which is a property of the material itself and indicates the relative ratio (red-brown) between viscosity and elasticity.

[0103] Referring to Fig. 12, the Storage modulus (G') of Example 1 was slightly lower than that of Comparative Example 1, indicating that Example 1 had relatively lower elasticity than Comparative Example 1. Accordingly, the cause of the tendency of Comparative Example 1 to clump together rather than adhere to the surface, as shown in the results of Experimental Example 1, could be numerically identified.

[0104] In the case of complex viscosity (η) and Tan delta, Example 1 was higher than Comparative Example 1, and it was found that there was a significant difference in viscosity compared to the elastic modulus, which did not show a significant difference. Accordingly, it was numerically confirmed that Example 1 had a high resistance to external physical stimulation after application and a high viscosity.

[0105] Referring to Fig. 13, in the case of storage modulus (G'), the highest elasticity was shown in Example 3, followed by Examples 2, 4, and 1 in that order. This shows that the content of camostat mesylate affects the elasticity of the formulation. Referring to Fig. 14, in the case of complex viscosity (η), the highest complex viscosity was shown in Example 3, followed by Examples 2, 4, and 1 in that order, in the same manner as the elastic modulus. This shows that the content of camostat mesylate also affects the complex viscosity.

[0106] The above results confirmed that differences occurred depending on the content of camostat mesylate, and that camostat mesylate improved surface adhesion and viscosity.

[0107]

[0108] Although exemplary embodiments of the present invention have been described in detail above, the scope of the present invention is not limited thereto, and various modifications and improvements made by those skilled in the art using the basic concept of the present invention defined in the following claims also fall within the scope of the present invention.

[0109] All technical terms used in this invention, unless otherwise defined, have the same meaning as commonly understood by those skilled in the art. The contents of all publications cited herein as references are incorporated herein by reference.

Claims

1. A composition for nasal spray comprising xanthan gum and camostat mesylate as active ingredients.

2. In paragraph 1, As a result of the analysis of the rotational rheometer (RHEOMETER(AR)) using a 60 mm cone plate, 10 3 ~10 5 A composition for nasal spray, wherein the difference between the viscosity measured under shear rate (1 / s) conditions and the viscosity measured under 1 shear rate (1 / s) conditions is 4 cp or more.

3. In paragraph 1, The results of the rotational rheometer (RHEOMETER(AR)) device analysis using a 40 mm cone plate were 10 3 ~10 5 A composition for nasal spray, wherein the viscosity measured when changing from a shear rate (1 / s) condition to a 1 shear rate (1 / s) condition is 4 cp or more.

4. In paragraph 1, A composition for nasal spray, wherein the above xanthan gum is contained in an amount of 0.01 to 0.04 wt% based on the total weight of the composition.

5. In paragraph 1, A composition for nasal spray, wherein the above camostat mesylate is contained in an amount of 0.02 to 0.10 wt% based on the total weight of the composition.

6. In paragraph 1, A composition for nasal spray, wherein the composition further comprises at least one selected from a preservative, an isotonic agent, a fragrance, a pH regulator, and a solvent. 7.(a) Step of sterilizing by heating the solvent; (b) A step of cooling the sterilized solvent to 45 to 55°C, adding a fragrance and a preservative, and performing a first mixing; (c) a step of adding a tonicity agent to the first mixed mixture and performing a second mixing; (d) a step of cooling the second mixed mixture to 20 to 30°C, then adding camostat mesylate and mixing it a third time; (e) Step of adding a pH adjuster to the above 3rd mixed mixture and titrating to pH 3 to 5; (f) a step of mixing xanthan gum into the pH-adjusted solution and then adding a sterilized solvent; and (g) A method for producing a composition for nasal spray, comprising the step of filtering the mixture to which the sterilized solvent is added.

8. In paragraph 7, A method for manufacturing a composition for nasal spray, wherein the first mixing is performed at 200 to 600 rpm for 30 to 90 minutes, and the second mixing and the third mixing are performed at 200 to 600 rpm for 10 to 60 minutes.

9. In paragraph 7, A method for manufacturing a composition for nasal spray, wherein mixing in the above step (f) is performed at 200 to 600 rpm for 90 to 150 minutes.

10. In paragraph 7, A method for manufacturing a composition for nasal spray, wherein filtration in the above step (g) is performed using a 5 to 10 μm filter.

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