Organosilicon quaternary ammonium salt oral ulcer wound spray and preparation method thereof

Abstract

The invention belongs to the field of antibacterial drugs, and particularly relates to an organosilicon quaternary ammonium salt oral ulcer wound spray and a preparation method thereof. The wound spray comprises the following components in parts by mass: 1-8 parts of polyvinyl alcohol, 1-3 parts of hydroxypropyl methylcellulose, 1-12 parts of chitosan, 2-5 parts of povidone, 1-3 parts of a plasticizer, 1-4 parts of sodium carboxymethyl cellulose, 3-10 parts of quaternary ammonium salt, 0.1-0.3 part of a penetrant, 2-4 parts of a film-forming agent, 1-3 parts of an accelerant, 1-4 parts of ferulic acid and 100-130 parts of a solvent. The invention also provides a specific preparation method. The problems that the existing oral ulcer treatment effect is poor and the period is long are solved, the synergistic effect of the accelerant and the penetrating agent is utilized, a protection system formed by quaternary ammonium salt and chitosan is effectively improved, the anti-inflammatory protection effect and the penetration absorption effect of oral ulcer wounds are improved in cooperation with the anti-oxidation and anti-inflammatory effects of ferulic acid, and the oral ulcer treatment effect is improved. The wound recovery speed is increased, and the period is shortened.

Description

Technical Field

[0001] The invention belongs to the technical field of antibacterial drugs, and in particular relates to an organosilicon quaternary ammonium salt oral ulcer wound spray and a preparation method thereof. Background Art

[0002] Oral ulcer is a common and frequently-occurring disease, and is the disease with the highest incidence rate among oral mucosal diseases. The current incidence rate of oral ulcer is more than 35%, and its characteristics are repeated attacks, burning pain, affecting the patient's normal diet, and can also cause a variety of complications. Most patients can heal themselves, but those with severe conditions last for a long time, and because of their repeated attacks, they bring great pain to patients. The cause of oral ulcer is unknown, and the cause of some patients is related to tension, trauma, smoking cessation, menstruation, and food allergies. Therefore, it is difficult to avoid the occurrence of oral ulcers through drug treatment. At present, alleviating headaches during oral ulcer attacks and accelerating the healing of oral ulcers have become the mainstream research direction. Products on the market, such as watermelon frost, lozenges, sprays, etc., cannot effectively and timely solve the problem of acute and long-lasting oral ulcers. Summary of the invention

[0003] In view of the problems in the prior art, the present invention provides an organosilicon quaternary ammonium salt oral ulcer wound spray, which solves the problems of poor treatment effect and long treatment period of the prior oral ulcer. The synergistic effect of the promoter and the permeation agent is utilized to effectively enhance the protection system formed by the quaternary ammonium salt and chitosan, and the antioxidant and anti-inflammatory effects of ferulic acid are combined to enhance the anti-inflammatory protection effect and the permeation absorption effect of the oral ulcer wound, thereby increasing the recovery speed of the wound and reducing the treatment period.

[0004] In order to achieve the above technical objectives, the technical solution of the present invention is: An organosilicon quaternary ammonium salt oral ulcer wound spray, the mass ratio of which is: 1-8 parts of polyvinyl alcohol, 1-3 parts of hydroxypropyl methylcellulose, 1-12 parts of chitosan, 2-5 parts of povidone, 1-3 parts of plasticizer, 1-4 parts of sodium carboxymethyl cellulose, 3-10 parts of quaternary ammonium salt, 0.1-0.3 parts of penetrant, 2-4 parts of film-forming agent, 1-3 parts of accelerator, 1-4 parts of ferulic acid, and 100-130 parts of solvent.

[0005] The polyvinyl alcohol is polyvinyl alcohol PVA17-88.

[0006] The plasticizer is glycerol.

[0007] The quaternary ammonium salt is an organosilicon quaternary ammonium salt.

[0008] The penetrant is dimethyl isosorbide.

[0009] The film-forming agent is polyvinyl butyral with a viscosity of 250-280 cps.

[0010] The promoter adopts a mixture of alanylglutamine and allantoin, and the mass ratio of the two is 3-5:1. The alanylglutamine has biological activities such as increasing the biosynthesis of glucosamine, aminohexose, and mucin and promoting the regeneration of ulcer tissue, and can also improve the body's metabolism and nitrogen balance, increase the total number of lymphocytes, effectively regulate immune response, improve the body's metabolic status, and enhance the body's antioxidant capacity. It has the effects of promoting cell growth, accelerating wound healing, and preventing the formation of scar tissue after ulcer healing.

[0011] The solvent is an ethanol aqueous solution, and the volume proportion of ethanol in the ethanol aqueous solution is 10-40%.

[0012] The preparation method of the organosilicon quaternary ammonium salt oral ulcer wound spray comprises the following steps: Step 1, adding hydroxypropyl methylcellulose to a 10-20% solvent and stirring evenly to form a gel solution, then adding a quaternary ammonium salt and a penetrant and stirring evenly to obtain a quaternary ammonium salt dispersed gel; the stirring speed for stirring evenly is 100-300r / min; this step utilizes the water solubility of hydroxypropyl methylcellulose to form an annual gel, and adds the quaternary ammonium salt and the penetrant, and the quaternary ammonium salt and the penetrant are homogeneously dispersed in the hydroxypropyl methylcellulose gel under stirring, Step 2, adding polyvinyl alcohol to a 20-30% solvent and stirring evenly, and adding ferulic acid and chitosan and stirring at a constant temperature for 20-30 minutes to obtain a polyvinyl alcohol mixed gel, wherein the stirring speed for the uniform stirring is 200-400 r / min, and the temperature for the constant temperature stirring is 40-60° C. The present invention utilizes the water solubility and gelation of polyvinyl alcohol itself to homogeneously disperse ferulic acid and chitosan in the gel system to obtain a polyvinyl alcohol gel with antibacterial and anti-inflammatory properties; Step 3, adding povidone and sodium carboxymethyl cellulose to the remaining solvent and stirring evenly, then adding plasticizer and accelerator in sequence and stirring at constant temperature to obtain a dispersion-promoting gel, wherein the stirring speed for uniform stirring is 100-300 r / min, and the temperature for constant temperature stirring is 20-30° C.; Step 4, adding the polyvinyl alcohol mixed gel into the dispersion promoting gel and stirring evenly, then adding the quaternary ammonium salt dispersion gel and stirring well to obtain a prefabricated spray; the stirring speed for stirring evenly is 300-500r / min; Step 5, adding the film-forming agent to the pre-made spray, stirring and dissolving it fully to obtain the oral ulcer wound spray.

[0013] It can be seen from the above description that the present invention has the following advantages: 1. The present invention solves the problems of poor treatment effect and long treatment cycle of existing oral ulcers. The synergistic effect of the promoter and the permeant is utilized to effectively enhance the protection system formed by the quaternary ammonium salt and chitosan, and the antioxidant and anti-inflammatory effects of ferulic acid are combined to enhance the anti-inflammatory protection and permeation absorption effects of the oral ulcer wound, thereby increasing the recovery speed of the wound and reducing the treatment cycle.

[0014] 2. The present invention uses alanyl-glutamine and allantoin as promoters, which can directly act on the oral ulcer wound, and is supplemented by the permeability of dimethyl isosorbide, ensuring that the promoter can penetrate into the wound, achieving synchronous healing inside and outside, and greatly improving the healing efficiency.

[0015] 3. The present invention utilizes chitosan and organosilicon quaternary ammonium salt as the main antibacterial and antimicrobial materials, and uses ferulic acid, alanyl-glutamine and isosorbide dimethyl ether as auxiliary antibacterial materials to form a composite antibacterial system, which cooperates with the antibacterial effect of the gel system of polyvinyl alcohol and polyvinyl butyral, thereby improving the adhesion and antibacterial properties of the spray on oral ulcer wounds.

[0016] 4. The present invention adopts ethanol aqueous solution as solvent, and cooperates with ferulic acid and polyvinyl butyral to relieve pain and inflammation, which plays a preliminary sterilization role while effectively reducing the irritation of ethanol to the wound.

[0017] 5. The present invention uses polyvinyl alcohol and hydroxypropyl methylcellulose as gelling agents to form a homogeneous dispersion of the bactericidal material and the promoting material, and then achieves encapsulation and fixation through the gel. Combined with the structural similarity and gel properties of sodium carboxymethyl cellulose and polyvinyl butyral, a breathable film is formed on the wound surface, achieving the characteristics of directional treatment and rapid absorption. DETAILED DESCRIPTION

[0018] The present invention is described in detail with reference to the embodiments, but no limitation is imposed on the claims of the present invention. Example 1 A silicone quaternary ammonium salt oral ulcer wound spray, the mass ratio of which is:

[0019] 1 part of polyvinyl alcohol, 1 part of hydroxypropyl methylcellulose, 1 part of chitosan, 2 parts of povidone, 1 part of plasticizer, 1 part of sodium carboxymethyl cellulose, 3 parts of quaternary ammonium salt, 0.1 part of penetrant, 2-4 parts of film-forming agent, 1 part of accelerator, 1 part of ferulic acid, and 100 parts of solvent.

[0020] The polyvinyl alcohol is polyvinyl alcohol PVA17-88.

[0021] The plasticizer is glycerol.

[0022] The quaternary ammonium salt is an organosilicon quaternary ammonium salt.

[0023] The penetrant is dimethyl isosorbide.

[0024] The film-forming agent is polyvinyl butyral with a viscosity of 250-280 cps.

[0025] The accelerator is a mixture of alanylglutamine and allantoin, and the mass ratio of the two is 3:1.

[0026] The solvent is an ethanol aqueous solution, and the volume proportion of ethanol in the ethanol aqueous solution is 10%.

[0027] The preparation method of the organosilicon quaternary ammonium salt oral ulcer wound spray comprises the following steps: Step 1, adding hydroxypropyl methylcellulose to a 10% solvent and stirring evenly to form a gel solution, and then adding a quaternary ammonium salt and a penetrant and stirring evenly to obtain a quaternary ammonium salt dispersed gel; the stirring speed for stirring evenly is 100 r / min; Step 2, adding polyvinyl alcohol to a 20% solvent and stirring evenly, and adding ferulic acid and chitosan and stirring at a constant temperature for 20 minutes to obtain a polyvinyl alcohol mixed gel, wherein the stirring speed for uniform stirring is 200 r / min, and the temperature for constant temperature stirring is 40° C.; Step 3, adding povidone and sodium carboxymethyl cellulose to the remaining solvent and stirring evenly, then adding plasticizer and accelerator in sequence and stirring at a constant temperature to obtain a dispersion-promoting gel, wherein the stirring speed for uniform stirring is 100 r / min, and the temperature for constant temperature stirring is 20° C.; Step 4, adding the polyvinyl alcohol mixed gel into the dispersion promoting gel and stirring evenly, and then adding the quaternary ammonium salt dispersion gel and stirring well to obtain a prefabricated spray; the stirring speed for stirring evenly is 300r / min; Step 5, adding the film-forming agent to the pre-made spray, stirring and dissolving it fully to obtain the oral ulcer wound spray. Example 2 A silicone quaternary ammonium salt oral ulcer wound spray, the mass ratio of which is:

[0028] 8 parts of polyvinyl alcohol, 3 parts of hydroxypropyl methylcellulose, 12 parts of chitosan, 5 parts of povidone, 3 parts of plasticizer, 4 parts of sodium carboxymethyl cellulose, 10 parts of quaternary ammonium salt, 0.3 parts of penetrant, 4 parts of film-forming agent, 1-3 parts of accelerator, 4 parts of ferulic acid, and 130 parts of solvent.

[0029] The polyvinyl alcohol is polyvinyl alcohol PVA17-88.

[0030] The plasticizer is glycerol.

[0031] The quaternary ammonium salt is an organosilicon quaternary ammonium salt.

[0032] The penetrant is dimethyl isosorbide.

[0033] The film-forming agent is polyvinyl butyral with a viscosity of 250-280 cps.

[0034] The accelerator is a mixture of alanylglutamine and allantoin, and the mass ratio of the two is 5:1.

[0035] The solvent is an ethanol aqueous solution, and the volume proportion of ethanol in the ethanol aqueous solution is 40%.

[0036] The preparation method of the organosilicon quaternary ammonium salt oral ulcer wound spray comprises the following steps: Step 1, adding hydroxypropyl methylcellulose to a 20% solvent and stirring evenly to form a gel solution, and then adding a quaternary ammonium salt and a penetrant and stirring evenly to obtain a quaternary ammonium salt dispersed gel; the stirring speed for stirring evenly is 300 r / min; Step 2, adding polyvinyl alcohol to a 30% solvent and stirring evenly, and adding ferulic acid and chitosan and stirring at a constant temperature for 30 minutes to obtain a polyvinyl alcohol mixed gel, wherein the stirring speed for the even stirring is 400 r / min, and the temperature for the constant temperature stirring is 60° C.; Step 3, adding povidone and sodium carboxymethyl cellulose to the remaining solvent and stirring evenly, then adding plasticizer and accelerator in sequence and stirring at a constant temperature to obtain a dispersion-promoting gel, wherein the stirring speed for uniform stirring is 300 r / min, and the temperature for constant temperature stirring is 30° C.; Step 4, adding the polyvinyl alcohol mixed gel into the dispersion promoting gel and stirring evenly, and then adding the quaternary ammonium salt dispersion gel and stirring well to obtain a prefabricated spray; the stirring speed for stirring evenly is 500r / min; Step 5, adding the film-forming agent to the pre-made spray, stirring and dissolving it fully to obtain the oral ulcer wound spray. Example 3 A silicone quaternary ammonium salt oral ulcer wound spray, the mass ratio of which is:

[0037] 5 parts of polyvinyl alcohol, 2 parts of hydroxypropyl methylcellulose, 8 parts of chitosan, 4 parts of povidone, 2 parts of plasticizer, 3 parts of sodium carboxymethyl cellulose, 8 parts of quaternary ammonium salt, 0.2 parts of penetrant, 2-4 parts of film-forming agent, 2 parts of accelerator, 3 parts of ferulic acid, and 120 parts of solvent.

[0038] The polyvinyl alcohol is polyvinyl alcohol PVA17-88.

[0039] The plasticizer is glycerol.

[0040] The quaternary ammonium salt is an organosilicon quaternary ammonium salt.

[0041] The penetrant is dimethyl isosorbide.

[0042] The film-forming agent is polyvinyl butyral with a viscosity of 250-280 cps.

[0043] The accelerator is a mixture of alanyl-glutamine and allantoin, and the mass ratio of the two is 4:1.

[0044] The solvent is an ethanol aqueous solution, and the volume proportion of ethanol in the ethanol aqueous solution is 30%.

[0045] The preparation method of the organosilicon quaternary ammonium salt oral ulcer wound spray comprises the following steps: Step 1, adding hydroxypropyl methylcellulose to a 15% solvent and stirring evenly to form a gel solution, and then adding a quaternary ammonium salt and a penetrant and stirring evenly to obtain a quaternary ammonium salt dispersed gel; the stirring speed for stirring evenly is 200 r / min; Step 2, adding polyvinyl alcohol to a 25% solvent and stirring evenly, and adding ferulic acid and chitosan and stirring at a constant temperature for 25 minutes to obtain a polyvinyl alcohol mixed gel, wherein the stirring speed for the even stirring is 300 r / min, and the temperature for the constant temperature stirring is 50° C.; Step 3, adding povidone and sodium carboxymethyl cellulose to the remaining solvent and stirring evenly, then adding plasticizer and accelerator in sequence and stirring at a constant temperature to obtain a dispersion-promoting gel, wherein the stirring speed for uniform stirring is 200 r / min, and the temperature for constant temperature stirring is 25° C.; Step 4, adding the polyvinyl alcohol mixed gel into the dispersion promoting gel and stirring evenly, and then adding the quaternary ammonium salt dispersion gel and stirring well to obtain a prefabricated spray; the stirring speed for stirring evenly is 400r / min; Step 5, adding the film-forming agent to the pre-made spray, stirring and dissolving it fully to obtain the oral ulcer wound spray.

[0046] Comparative Example 1 Comparative Example 1 uses the oral ulcer spray purchased on the market - Kaihoujian spray.

[0047] Comparative Example 2 Comparative Example 2 uses a commercially available oral ulcer spray - watermelon frost spray.

[0048] Performance Testing The performance test was carried out using the sprays of Examples 1-3 and the sprays of Comparative Examples 1-2 as test samples. The method of using the spray is: Clean your mouth, open the spray bottle, and spray the oral ulcer spray on the wound at a dosage of 0.3-0.4 mL per square centimeter, until the normal skin is about 0.5 cm away from the edge of the wound, and wait for the solvent to evaporate and form a film.

[0049] 2-3 month old healthy male SD rats were used as test samples and were divided into 7 groups with 10 rats in each group. The first group was the normal group, the second, third and fourth groups were the oral ulcer test groups, the fifth and sixth groups were the oral ulcer control groups, and the seventh group was the oral ulcer untreated group.

[0050] The second, third, fourth, fifth, sixth and seventh groups were selected and 3 mm diameter filter paper dipped in 40% glacial acetic acid was applied to the lower lip of the right corner of the mouth of the rats for 1 minute, and then rinsed with saline for 1 minute. After 24 hours, an ulcer of about 3 mm diameter was observed on the right corner of the mouth of the rats, with a yellow-white surface covered with pseudomembrane and congestion and edema at the edge. The first group was fed normally and no treatment was given.

[0051] Drug administration: the first group received no treatment, the second to fourth groups were treated with the sprays of Examples 1-3, the fifth and sixth groups were treated with the sprays of Comparative Examples 1 and 2, respectively, and the seventh group was treated with physiological saline.

[0052] The healing time of oral ulcers in rats from group 2 to group 7 was observed. The healing criteria were the disappearance of redness and swelling on the ulcer surface, the shedding of pseudomembranes, and the continuity of epithelium. The mental state of the rats after medication was observed. The specific results are as follows: Ulcer healing time (d) Mental state Ulcer condition Pain (first time) Group 1 / good / obvious Group 2 3-4 good Visible reduce Group 3 2-3 good Visible reduce Group 4 3-4 good Visible reduce Group 5 6-7 Restlessness Visible obvious Group 6 6-7 Slightly agitated Invisible reduce Group 7 9-10 Restlessness Visible obvious The above data show that the comparison between the first and seventh groups shows that oral ulcers can heal themselves in about 9 days without medication, and the experimental mice became agitated during the healing process because the oral ulcer wounds were painful. The fifth group (Comparative Example 1) contained ethanol, and the content was not low, which was irritating to the wound. The particle size of the powder in the sixth group would reduce the contact area, effectively reducing the irritation and pain.

[0053] Comparison between the second to fourth groups and the fifth to seventh groups shows that the spray of this solution promotes the healing of oral ulcers and shortens the healing period, indicating that the healing time of the present invention is relatively short and has a more excellent healing effect. At the same time, the spray has good analgesic properties, ensuring that the experimental mice are in a good mental state, indicating that the present invention has an analgesic function. The oral ulcer spray of the present invention forms a protective film on the surface of the ulcer, making the ulcer visible and being able to observe the ulcer healing at all times.

[0054] It is understood that the above specific description of the present invention is only used to illustrate the present invention and is not limited to the technical solutions described in the embodiments of the present invention. Those skilled in the art should understand that the present invention can still be modified or replaced by equivalents to achieve the same technical effects; as long as the use requirements are met, they are within the protection scope of the present invention.

Claims

1. An organosilicon quaternary ammonium salt oral ulcer wound spray, characterized in that: The mass ratio is: 1-8 parts of polyvinyl alcohol, 1-3 parts of hydroxypropyl methylcellulose, 1-12 parts of chitosan, 2-5 parts of povidone, 1-3 parts of plasticizer, 1-4 parts of sodium carboxymethyl cellulose, 3-10 parts of quaternary ammonium salt, 0.1-0.3 parts of penetrant, 2-4 parts of film-forming agent, 1-3 parts of accelerator, 1-4 parts of ferulic acid and 100-130 parts of solvent; the quaternary ammonium salt is an organosilicon quaternary ammonium salt.

2. The organosilicon quaternary ammonium salt oral ulcer wound spray according to claim 1, characterized in that: The polyvinyl alcohol is polyvinyl alcohol PVA17-88.

3. The organosilicon quaternary ammonium salt oral ulcer wound spray according to claim 1, characterized in that: The plasticizer is glycerol.

4. The organosilicon quaternary ammonium salt oral ulcer wound spray according to claim 1, characterized in that: The penetrant is dimethyl isosorbide.

5. The organosilicon quaternary ammonium salt oral ulcer wound spray according to claim 1, characterized in that: The film-forming agent is polyvinyl butyral with a viscosity of 250-280 cps.

6. The organosilicon quaternary ammonium salt oral ulcer wound spray according to claim 1, characterized in that: The promoter is a mixture of alanylglutamine and allantoin, and the mass ratio of the two is 3-5:

1.

7. The organosilicon quaternary ammonium salt oral ulcer wound spray according to claim 1, characterized in that: The solvent is an ethanol aqueous solution, and the volume proportion of ethanol in the ethanol aqueous solution is 10-40%.

8. The organosilicon quaternary ammonium salt oral ulcer wound spray according to claim 1, characterized in that: The preparation method of the organosilicon quaternary ammonium salt oral ulcer wound spray comprises the following steps: Step 1, adding hydroxypropyl methylcellulose to a 10-20% solvent and stirring evenly to form a gel solution, and then adding a quaternary ammonium salt and a penetrant and stirring evenly to obtain a quaternary ammonium salt dispersed gel; the stirring speed for stirring evenly is 100-300 r / min; Step 2, adding polyvinyl alcohol to a 20-30% solvent and stirring evenly, and adding ferulic acid and chitosan and stirring at a constant temperature for 20-30 minutes to obtain a polyvinyl alcohol mixed gel, wherein the stirring speed for the even stirring is 200-400 r / min, and the temperature for the constant temperature stirring is 40-60° C.; Step 3, adding povidone and sodium carboxymethyl cellulose to the remaining solvent and stirring evenly, then adding plasticizer and accelerator in sequence and stirring at constant temperature to obtain a dispersion-promoting gel, wherein the stirring speed for uniform stirring is 100-300 r / min, and the temperature for constant temperature stirring is 20-30° C.; Step 4, adding the polyvinyl alcohol mixed gel into the dispersion promoting gel and stirring evenly, then adding the quaternary ammonium salt dispersion gel and stirring well to obtain a prefabricated spray; the stirring speed for stirring evenly is 300-500r / min; Step 5, adding the film-forming agent to the pre-made spray, stirring and dissolving it fully to obtain the oral ulcer wound spray.