CN111700887A - A stupid sulfonic acid preparation for treating mucosal rupture - Google Patents

Abstract

The invention discloses a benzenesulfonic acid preparation for treating mucosal rupture, which is prepared by uniformly mixing 70-90% of benzenesulfonic acid, 8-20% of water and 2-10% of colloidal silicon dioxide by weight. The invention mainly adopts the monoaromatic sulfonic acid which has strong water absorbability and can remove the biofilm from the surface to effectively kill bacteria. The present formulation provides real-time pain relief and accelerated ulcer healing for the user, kills infectious microorganisms, i.e., they seek and attack necrotic or damaged tissue, quickly draws water away from the affected area, forms a protective layer, relieves pain, prevents contamination and aids healing, achieves the effect of drawing water away from the affected area through physical action, removes damaged tissue, and is therefore very effective in a single application with an ulcer or other mucosal end. Only contains one aromatic sulfonic acid, has simpler formula, is safer and has lower risk factors.

Description

A stupid sulfonic acid preparation for treating mucosal rupture

technical field

The invention relates to the technical field of medicines, in particular to a medicine for treating oral ulcer mucosal rupture.

Background technique

Oral ulcer is a common ulcerative injury disease that occurs in the oral mucosa. It is more common in the inner lip, tongue, tongue abdomen, buccal mucosa, vestibular sulcus, soft palate and other parts. For long-term or recurring oral ulcers, local anti-inflammatory, oral pain relief, and promotion of ulcer healing are generally used. However, the currently used drugs mainly have the following shortcomings. First, the effect is slow. Even pain relief requires repeated use for several days to relieve pain, not to mention wound healing, especially traditional Chinese medicine. Second, it is used for the treatment of chronic wounds. and bacterial infections often contain sulfuric acid, for example, topical ointments containing steroids for anti-inflammatory, and sulfuric acid and two sulfonic acid formulations can cause many colorants, fragrances and fragrances to be unstable and degrade over time, creating some risk factors , not only will reduce the efficacy of the drug itself, but also have potential safety hazards, which is more common especially with western medicine.

SUMMARY OF THE INVENTION

The technical problem to be solved by the present invention is aimed at the shortcomings of the prior art, and provides a simple formula, contains only one aromatic sulfonic acid, does not contain sulfuric acid, has higher safety, and has a faster effect. Acid preparations.

In order to solve the above-mentioned technical problems, the present invention adopts the following technical scheme: a benzene sulfonic acid preparation for treating mucosal fracture, characterized in that: by weight, benzene sulfonic acid is 70-90%, water is 8-20% and The colloidal silicon dioxide is 2-10%, and the above three raw materials are mixed uniformly to prepare a preparation; the preparation process is: in a clean indoor environment, the temperature is at room temperature (such as about 25°C), and the relative humidity is 55-65%. After weighing benzenesulfonic acid, water and colloidal silicon dioxide, add them into a container and heat to 90°C, stir for 1 hour until they are completely melted and evenly mixed, and the solution can be used after it is naturally cooled to room temperature.

The prepared preparation was heated to 30°C, and then the quantitative preparation was directly injected into the polypropylene container; finally, the pure aluminum foil film was heated to 120-150°C to seal the preparation in the polypropylene container.

Preferably, benzene sulfonic acid is 80%, water is 10%, and colloidal silica is 10%.

Pack a cotton swab in a polypropylene container for single use.

How to use: 1. Clean the affected area with an ordinary clean cotton swab or paper towel, so that the preparation can exert the best effect;

2. Open the tin foil from the package, and use the cotton swab in the package to stick an appropriate amount of preparation;

3. Apply the cotton swab with this preparation to the affected area for 3-5 seconds. Use the rolling method to completely cover the preparation drug on the affected area. Do not use the preparation to apply it to the affected area, and also avoid applying it to the non-affected area, so as to avoid possible redness and swelling of the oral mucosa;

4. After 3-5 seconds, rinse your mouth thoroughly with water, and the pain will disappear completely.

The present invention mainly adopts mono-aromatic sulfonic acid, which has strong water absorption, can remove biological film from the surface, and effectively kill bacteria. This formula provides the user with immediate pain relief and accelerated ulcer healing. The formula kills infectious microbes, i.e. they seek out and attack dead or damaged tissue, quickly drawing water away from the affected area, creating a protective layer that soothes Pain, prevent contamination and aid healing, achieve the effect of physically drawing water from the affected area, removing damaged tissue, so it is very effective in a single application with ulcers or other mucosal terminals.

At the same time, the formulation of the present invention contains only one aromatic sulfonic acid and does not contain sulfuric acid, and the formulation using a single sulfonic acid has the same benefits as the formulation using two sulfonic acids, but the formulation is simpler. In addition, because the preparation of the present invention does not contain sulfuric acid, it avoids the problem that various colorants, fragrances and fragrances are unstable and degrade over time due to the instability of sulfuric acid and two sulfonic acid preparations, and the application of colorants, fragrances and fragrances is avoided. Wider and safer, with lower risk factors.

Description of drawings

Fig. 1 is a comparison table of no obvious pain scores in patients treated with HybenX (the present invention) and Salicept (existing drug oral patch);

Figure 2 shows that the drug forms a protective layer of coagulated tissue fragments on the ulcer surface by placing the tip of a cotton swab on the ulcer for 10 seconds.

Detailed ways

Further description is given below in conjunction with specific implementations:

Embodiment 1, the benzene sulfonic acid preparation for the treatment of mucous membrane fracture, by weight, benzene sulfonic acid is 70%, water is 20% and colloidal silicon dioxide is 10%, and the aforementioned three raw materials are mixed uniformly to prepare preparation.

In an indoor clean environment, the temperature is at room temperature (such as about 25°C), and the relative humidity is 60%. After weighing the benzenesulfonic acid, water and colloidal silica, add them to the container and heat to 90°C, and stir for 1 hour to complete Dissolve and mix evenly, wait for the solution to cool to room temperature before use.

The prepared preparation was heated to 30°C, and then the quantitative preparation was directly injected into a polypropylene container of a specific shape; finally, the pure aluminum foil film was heated to 120-150°C to seal the preparation in the polypropylene container.

Pack a cotton swab in a polypropylene container for single use.

Example 2, the difference is that, by weight, benzenesulfonic acid is 80%, water is 10%, and colloidal silicon dioxide is 10%, and the aforementioned three raw materials are mixed uniformly to prepare a preparation.

Example 3, the difference is that, by weight, benzene sulfonic acid is 90%, water is 8% and colloidal silicon dioxide is 2%, and the aforementioned three raw materials are mixed uniformly to prepare a preparation.

How to use: 1. Clean the affected area with an ordinary clean cotton swab or paper towel, so that the preparation can exert the best effect;

2. Open the tin foil from the package, and use the cotton swab in the package to stick an appropriate amount of preparation;

3. Apply the cotton swab with this preparation to the affected area for 3-5 seconds. Use the rolling method to completely cover the preparation drug on the affected area. Do not use the preparation to apply it to the affected area, and also avoid applying it to the non-affected area, so as to avoid possible redness and swelling of the oral mucosa;

4. After 3-5 seconds, rinse your mouth thoroughly with water, and the pain will disappear completely. Preferably, benzene sulfonic acid is 80%, water is 10%, and colloidal silica is 10%.

Pack a cotton swab in a polypropylene container for single use.

How to use: 1. Clean the affected area with an ordinary clean cotton swab or paper towel, so that the preparation can exert the best effect;

2. Open the tin foil from the package, and use the cotton swab in the package to stick an appropriate amount of preparation;

3. Apply the cotton swab with this preparation to the affected area for 3-5 seconds. Use the rolling method to completely cover the preparation drug on the affected area. Do not use the preparation to apply it to the affected area, and also avoid applying it to the non-affected area, so as to avoid possible redness and swelling of the oral mucosa;

4. After 3-5 seconds, rinse your mouth thoroughly with water, and the pain will disappear completely.

A randomized controlled trial of the present invention (HybenX) for the treatment of recurrent aphthous stomatitis:

Trial Unit: Research in Oral Medicine and Health Services, Eastman Institute of Dentistry, University of London, London, UK.

Background: Treatment of recurrent aphthous stomatitis (RAS) is primarily aimed at reducing pain and the duration of each ulcer episode, however, there are still a few medications with clear evidence of benefit.

Objectives: The objective of this study was to determine the efficacy of the present invention (HybenX) versus another commonly used drug for the treatment of RAS (Salicept Oral Patch, Carrington Laboratories, Inc., Irvine, TX, USA), To reduce the symptoms and duration of RAS, and to determine the safety of HybenX for clinical use.

MATERIALS AND METHODS: Sixty-three persons (36 men, 27 women, mean age 25 years, range 17.8-57.9 years) were included in a randomized controlled trial comparing HybenX with the Salicept oral patch.

RESULTS: At 5 days after treatment, the two drugs had few side effects in both phases of pain symptom reduction—a total of 9 adverse events were recorded in 8 patients, but these were unlikely to be related to the treatment device. HybenX should only be used in the HybenX group, while individuals in the Salicept group were able to make drug claims. The average number of Salicept patches used per subject per day was 3 on day 1 (s.d.3.3), 3.4 on days 2 and 2.7 (s.d.3.1), and on days 2 and 2.7 (s.d.1.9) on days 2 and 2. Day 2.7. After that, the number on day 7 dropped to an average of 0.8.

Conclusion: HybenX can safely and effectively relieve pain symptoms in RAS patients.

The etiology of recurrent oral ulcers is unclear, and most patients have no clear etiology. Some patients experience worsening ulcers following oral trauma (eg, vigorous cleaning of teeth or dental treatment). Others may suffer from increased RAS events caused by smoking cessation (McCullo et al., 2007) or psychological stress (Scully, 2006). Suggested etiological factors include family history of RAS, idiopathic hemoglobin deficiency and, more rarely, food sensitivities, immunodeficiency, menstrual cycle variability, and possible infant feeding practices (McCullough et al., 2007).

Currently, thalidomide is the only drug that has successfully prevented RAS recurrence (Jurge et al., 2006; Scully and Porter, 2008). However, ulcers often recur when treatment is discontinued, and the well-known side effects of thalidomide, particularly teratogenic and peripheral neuropathy liability, limit its clinical application to specialist practice (Porter and Jorge, 2002). Therefore, treatment is primarily aimed at reducing the duration and pain of the ulcer. Typical treatments include chlorhexidine gluconate (0.2%) mouthwash, topical corticosteroids (eg, 1% carboxycellulose paste or betamethasone or prednisolone mouthwash) and topical minocycline (high Erski, 2007).

A randomized controlled comparison with another drug (Salicept) for the treatment of this ulcer. In addition, the study sought to determine the performance and safety of HybenX in the treatment of RAS.

Materials and methods

ethical approval

It consisted of 53 healthy adults over 18 years of age with a history of RAS (Porter and Scully, 2005). Specifically, all subjects had a history of recurrent episodes of ulceration of the nonkeratinized oral mucosa, including two episodes in the past 12 months. None of the subjects had ulcers of any local cause and a history of infectious, hematological, gastrointestinal or dermatological conditions that could cause oral mucosal ulcers. All study subjects received medication that could lead to oral mucosal ulceration (Scully et al., 2003). During the study, all subjects agreed to avoid other oral ulcer treatments (ie, topical or systemic anti-inflammatory or analgesics (such as aspirin, paracetamol, or ibuprofen), corticosteroids, pain relievers, alcohol-based or narcotic-containing drugs mouthwash) and tooth bleach. All female patients had a pregnancy test prior to study entry, and women found to be pregnant did not enter the study.

research proposal

At study entry, all subjects had at least one oral mucosal ulcer for less than 48 hours. At baseline, the size, location, color, and depth of each ulcer were estimated clinically and via photographs and subjects were asked to estimate pain intensity on a 100-mm Visual Analog Scale (VAS; baseline noncontroversial pain assessment). Subjects then held 20 ml of natural orange juice over the ulcerated area for more than 5 seconds, then swallowed or coughed up the juice. A further VAS (Baseline Challenge Pain Assessment) was then recorded and each subject was then randomly assigned to either HybenX or Salicept followed by a single application of HybenX or Salicept to the ulcer by the clinician. This was followed by an unchallenged VAS (unchallenged pain assessment after immediate treatment) and a recording of a challenged pain assessment. Further estimates of unchallenged and challenged VAS were made 20 minutes after application of the drug (20 minutes post-processing of unchallenged and challenged pain assessments).

The subject was subsequently discharged from the hospital. Subjects in the Salicept group were instructed on appropriate home self-administration of Salicept - these could be used as often as the subjects wished. Subjects in the HybenX group did not receive any additional equipment. All over the next 8 days, subjects were asked to complete a VAS with the highest estimated score each day - this was done before they went to bed. The Salicept group also recorded the number of Salicept use received per day. The researcher was contacted by phone to remind him/her of these tasks, and all subjects also recorded any potential side effects of HybenX or Salicept.

On day 8 after treatment, all subjects were examined by clinicians, masking treated patients to determine the size, degree of healing of oral mucosal ulcers by comparison with baseline clinical notes and photographs. After day 8 of treatment, pain assessments for unchallenged and challenged were performed. In addition, patients completed self-administered questionnaires about their satisfaction with the treatment provided by the device they received.

Based on statistical analysis of pain assessments in patients taking the drug in combination with HybenX, the mean change from baseline in the two active arm VAS was observed, with a sample size of at least 22 per treatment group, to examine both pre- and post-treatment pain scores in both groups 15mm difference. This hypothesis is a two-sided test with 80% power at the 5% significance level. Changes from baseline in VAS pain scores were compared between HybenX and Salicept at all indicated time points and compared with HybenX and Salicept for unchallenged pain scores and challenged pain scores, respectively. Pain scores recorded on a 100-mm scale were considered an ongoing outcome. The differences in pain scores between treatment groups at each time point were compared by Student's t-test.

To assess the overall effect of uncontroversial pain score treatment (including all time points), repeated measures regression models were fitted to each patient's pain score at each time. Covariates included an intercept, an indicator for the HybenX treatment group, time to assessment (values 0-8), time to assess interaction by treatment group and baseline preconditioning pain score. The proportion of patients with complete healing of all ulcers at day 8 was compared in the treatment groups using Fisher's exact test and was assessed by the assessor who was asked. Days to ulcer healing (subjects) using a Cox proportional hazards model to compare perception between treatment groups. The model included HybenX treatment for one indicator variable. Hazard ratio estimates >1 indicate that HybenX patients perceive faster healing.

Pain assessments for the number of Salicept drugs reapplied after challenge were summarized by treatment group. Similarly, daily diary information about the amount used each day.

Changes in general health were calculated for each patient as follows: For each body system assessed at screening and physical examination on Day 8, a score of 0 (no change), 1 (new condition reported on Day 8 was assigned ) or -1 point (unreported screening on day 8). The sum of the scores was used to measure changes in overall health. The total health score for each patient was calculated between treatment groups using a (nonparametric) two-sample Wilcoxon rank test, as scores were not normally distributed for comparison. Given the low number of adverse events, no statistical analysis was performed to compare their incidence between treatment groups. Instead, a full list of adverse events and their full descriptions are provided.

achievement

63 patients participated in the study. Thirty-two patients (19 males, median age 23.1 years, 18.3-57.9 years old) were randomly divided into HybenX group, and 31 patients (17 males, median age 27 years, 17.8-53.4 years old) belonged to Salicept group. Eight subjects in the HybenX group were ultimately excluded when they developed new ulcers during the study, so the final HybenX group included 24 patients (14 males, mean age 23.1 years, 20 to 47.6 years). In the Salicept group, two patients were also excluded because they developed new ulcers, so the final Salicept group included 29 subjects (17 males, mean age 27 years, 17.8 to 53.4 between the ages). Baseline characteristics such as gender, age, medical history, concomitant medication, pulse, blood pressure, and respiratory rate, and the number, size, color, or estimated depth of ulcers (no differences in data) were not statistically significant between the two groups.

Pain scores before, immediately after, and 20 minutes after treatment

There was no disputed pain score before treatment, and there was no statistical difference between the two groups at 20 minutes and 8 days after treatment as shown in Table 1, although there was a greater trend in pain in the HybenX group than in the Salicept group. A pattern of increased scores for HybenX after application of similar Salicept observations is shown in Table 2, although it was noted that the HybenX group had a greater preconditioning challenge score (P=0.025).

Uncontroversial treatment pain scores on days 1-8

Patient-recorded declines in pain scores are detailed in Table 3 and Figure 1. The decrease in mean pain scores in the HybenX group was statistically greater than in the Salcept group (P=0.007) on Day 1 (P=0.016) and Day 2 (P=0.007), as detailed in Figure 1 . HybenX caused an initial rise in pain (as indicated by negative values), which may reflect the initial tingling sensation after application. However, over the next two days, HybenX was the more effective pain-relieving drug of the two.

Subjective evaluation of ulcer healing

By day 8, 50% of HybenX subjects and 44.4% of Salicept subjects had complete healing of all ulcers, a difference that was not statistically significant. The mean closure rate of the largest ulcers also did not differ significantly between the two groups. The cumulative percentage of HybenX patients was higher except on day 4.

Table 1 Summary of pain reduction without challenge in patients treated with HybenX or Salicept before treatment, immediately after treatment, 20 minutes after treatment, and on day 8 after treatment

Table 2 Summary of pain reduction difficulties in patients receiving HybenX or Salicept before treatment, immediately after treatment, 20 minutes after treatment, and on day 8 after treatment

The ulcer was considered healed, but the perceived pain was not statistically different between the two groups, as shown in Table 4.

Safety

Nine adverse reactions in eight patients were recorded. All of these are unlikely to be related to the therapeutic device. Five adverse reactions in the HYbenX group included possible common cold (2 cases), sore throat (1 case), cough (1 case), and ankle sprain (1 case). Four adverse reactions in the salicept group were dyspepsia and diarrhea (two events in one patient), traumatic lower lip lesions (one patient), and hay fever (one patient).

acceptability

The reported reduction in subjects using Salicept was primarily due to a reduction in their clinical need, although other reasons included application inconvenience, being too busy or forgetting to use the patch.

discuss

Recurrent aphthous stomatitis remains a difficult disease to treat. Since the exact cause is unknown, there is still no specific, safe, and effective means to stop ulcers from erupting, so almost all treatments are aimed at reducing the pain symptoms and duration of ulcers. Patients may seek appropriate treatment from a variety of sources, and often self-medicate with a range of medications.

Table 3 Summary of pain relief after treatment in subjects receiving Hybenx or Salicepta

Table 4 Cumulative ulcer healing in subjects treated with HybenX or Salicept

Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 HybenX(n=24) 3 (12.5%) 6 (25.0%) 10 (41.7%) 14 (58.3%) 16 (66.7%) 19 (79.2%) SaliCept (n=29) 2 (7.7%) 3 (12.0%) 9 (34.0%) 10 (38.5%) 13 (52.0%) 15 (62.5%)

The percent response of patients on each study day in each group was calculated.

There is still no systematic review of the treatment of RAS, although a wide range of drugs are considered to have some benefit, and the mainstays of treatment are topical corticosteroids and antibiotics. For example chlorhexidine, however, there is little substantial data on the former and the latter may cause unpleasant bitterness and external staining of teeth. Newer drugs include topical minocycline and amlexanox. The latter, in some but not all formulations, have been found to reduce clinical signs and symptoms. Symptoms of RAS, especially in the development of ulcers in the prodromal stage, but this preparation is not widely used in all countries. Therefore, as with herpes cheilitis, topical medications have therapeutic properties and can be easily applied to the site of pain or facial disease in affected individuals, which will safely reduce painful symptoms and be widely available to the public.

Previous findings suggest that chemical cautery or coagulation may be of clinical benefit in the treatment of RAS, however, it is unclear whether there is any method of treatment randomization. This study explores that HybenX can conveniently release the solution from the chemically coagulated ulcer area, approximately 0.2 ml of cautery solution is delivered from the hollow shaft of the cotton swab to the tip, and then placed on the ulcer for 10 seconds (Figure 2). The HybenX solution includes free sulfate and sulfonated aromatics, especially hydroxybenzenesulfonic acid, hydroxymethoxybenzenesulfonic acid, and concentrated aqueous solutions of pyruvic acid. Hydrobenzane is angularly soluble, while sulfonic acid groups and sulfuric acid are hygroscopic and denaturing. Application to the ulcerated area results in denaturation, precipitation and coagulation of the tissue fragments on the ulcer surface and the formation of a protective layer of coagulated tissue fragments on the ulcer surface, thereby reducing local discomfort to painful stimuli, this protective surface fragmentation during the healing process absorbed in.

This study was a prospective randomized trial with an appropriate number of subjects selected to achieve the desired statistical strength. Age, sex, RAS, and associated pain symptoms were comparable between the two groups at the start of the study. The results showed that topical application of HybenX significantly reduced RAS pain after 2 days compared to a patch designed to protect the area of mouth ulcers (Salicept). HybenX and Salicept caused reductions in unchallenged pain scores between Days 1 and 4, but HybenX's reductions were always greater. It was confirmed that HybenX may be similar to Salicept in that it creates a physical barrier that relieves discomfort caused by localized painful stimuli. Immediate treatment of challenged and unchallenged pain in the HybenX group is expected to be greater than in the Salicept group because the former is acidic, while the latter provides a bland coverage and the currently observed benefit of HybenX appears to exceed the increased local pain after brief treatment.

Although not the primary goal of this study, the performance of the two drugs in helping ulcer healing was evaluated. It has been previously reported that Debicone induces early RAS healing more quickly than topical glucocorticoid paste or no treatment. In the present study, there was no difference in patients' perception of ulcer healing between days 1-7 of the study period, and no difference in ulcer healing on day 8, observed by clinician masking of the trial treatment. The results of these comparisons may reflect differences in the drugs used due to the higher sulfuric acid content than benzenesulfonic acid, but it is doubtful that this is the mechanism of enhanced healing as this acidity aids tissue necrosis. The contrasting results may reflect the control agents/devices used in the two studies, but it is also difficult to understand how these changes explain the different healing outcomes. The effect of this drug on nerve endings is unknown, so it is unclear whether HybenX is in part responsible for the pain relief due to local nerve activity. The current results reflect patient perceptions, whereas earlier studies were based on a more accurate examination by clinicians. That's it. The current findings may underscore the impact of HybenX (and/or Salicept) on ulcer healing. There was no correlation between time to ulcer onset and initiation of treatment with either drug. However, early application of HybenX will speed up the pain relief of this type of ulcer.

The present invention has been described in detail above. The above are only preferred embodiments of the present invention, and should not limit the scope of implementation of the present invention, that is, all equivalent changes and modifications made according to the scope of the application should still belong within the scope of the present invention.

Claims (4)

1. a stupid sulfonic acid preparation for the treatment of mucosal fracture, is characterized in that: by weight, benzenesulfonic acid is 70-90%, and water is 8-20% and colloidal silicon dioxide are 2-10%, The aforesaid three raw materials are mixed uniformly and prepared into a preparation; The preparation process is as follows: under the conditions of normal temperature and relative humidity of 55-65%, add benzenesulfonic acid, water and colloidal silicon dioxide into a container and heat to 90 ° C, stir until completely dissolved and evenly mixed, and wait for the solution to naturally cool to room temperature. can be used later. 2. The stupid sulfonic acid preparation for treating mucosal rupture according to claim 1, wherein the prepared preparation is heated to 30°C, and then the quantitative preparation is directly injected into a polypropylene material container; The aluminum foil film was heated to 120-150°C to seal the formulation in a polypropylene container. 3. The stupid sulfonic acid preparation for treating mucosal fracture according to claim 1, wherein the benzene sulfonic acid is 80%, the water is 10%, and the colloidal silicon dioxide is 10%. 4. The stupid sulfonic acid preparation for treating mucosal rupture according to claim 2, wherein a cotton swab is placed in the polypropylene material container for one-time use.

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