Application of polyoxyethylene particles in preparation of patch preparation for promoting oral mucosa injury repair

Abstract

The invention provides an application of polyoxyethylene particles in preparation of a patch preparation for promoting oral mucosa injury repair, and the weight-average molecular weight of polyoxyethylene is 1 million Dalton to 7 million Dalton; the average particle size of the polyoxyethylene particles is 0.5 [mu] m to 2000 [mu] m; the patch preparation is configured to form colloid covering the damaged wound surface of the oral mucosa after being applied to the damaged wound surface of the oral mucosa, so that the oral mucosa can be effectively protected, and the repair of the damaged wound surface of the oral mucosa is promoted.

Description

Technical Field

[0001] The present invention relates to the medical use of polyoxyethylene. Specifically, the present invention relates to the application of polyoxyethylene particles in the preparation of a biocompatible patch preparation for promoting the repair of oral mucosal injury. Background Art

[0002] In people's daily life, oral ulcer is a common ulcerative injury disease, and its occurrence is the result of the combined action of multiple factors. These include mucosal injury caused by external factors, malnutrition, hormonal level changes, vitamin or trace element deficiencies, systemic diseases, etc. Once oral mucosal injury occurs, patients often feel extremely painful, which affects daily diet and conversation, causing great inconvenience to daily life. In addition, when people have oral ulcers, they often unconsciously lick the wound, which not only causes mechanical irritation to the wound surface, increases the ulcer area, slows down the wound healing, but also increases the risk of bacterial infection.

[0003] Currently, the commonly used methods for treating oral ulcers mainly include the following aspects: ① reducing swelling and relieving pain, such as drugs like oral ulcer powder, watermelon frost, cydiodine buccal tablets, etc.; ② anti-inflammatory, such as anti-inflammatory drugs like metronidazole buccal tablets; ③ promoting ulcer healing, such as compound chlorhexidine dexamethasone film, compound vitamin B, etc. In addition, there are also methods of using traditional Chinese medicine powder and medicine film to treat oral ulcers. However, the commonly used treatment drugs at present have problems such as poor adhesion effect and short duration. In the human oral environment, the drugs under the combined action of various factors such as temperature and salivary amylase are enzymatically hydrolyzed and absorbed, so they cannot achieve the expected therapeutic effect in terms of mucosal protection and promoting healing. Patients often need to continuously change and supplement drugs to achieve the purpose of relieving pain and promoting healing. Therefore, there is an urgent need in this field for a biocompatible preparation with strong adhesion and capable of promoting the repair of oral mucosal injury for a long time.

[0004] Regarding polyoxyethylene, although the prior art discloses its use for hemostasis, there has been no report on using polyoxyethylene for promoting the repair of oral mucosal injury. Summary of the Invention

[0005] The purpose of the present invention is to provide a medical use of polyoxyethylene particles, that is, the application of polyoxyethylene particles in the preparation of a biocompatible patch preparation for promoting the repair of oral mucosal injury, wherein:

[0006] The weight-average molecular weight of the polyoxyethylene is 1 million to 7 million Daltons;

[0007] The average particle size of the polyoxyethylene particles is 0.5 μm to 2000 μm;

[0008] The patch preparation is configured to form a colloid covering the damaged wound surface of the oral mucosa after being applied to the damaged wound surface of the oral mucosa.

[0009] In some embodiments of the present invention, the average particle size of the polyethylene oxide particles is 50 - 500 μm.

[0010] In some embodiments of the present invention, the adhesion force of the colloid to the oral mucosa is not less than 1 N.

[0011] In some embodiments of the present invention, the patch preparation further comprises at least one of polysaccharide, polyvinylpyrrolidone, and carbomer.

[0012] In some embodiments of the present invention, the patch preparation further comprises polysaccharide, and the mass ratio of polyethylene oxide to polysaccharide is 9:1 to 7:3.

[0013] In some embodiments of the present invention, the patch preparation further comprises polyvinylpyrrolidone, and the mass ratio of polyethylene oxide to polyvinylpyrrolidone is 9:1 to 7:3.

[0014] In some embodiments of the present invention, the patch preparation further comprises carbomer, and the mass ratio of polyethylene oxide to carbomer is 9:1 to 7:3.

[0015] In some embodiments of the present invention, the patch preparation comprises polysaccharide, polyvinylpyrrolidone, and carbomer, and in this patch preparation, the mass percentage content of the polyethylene oxide particles is 99% to 70%; the mass percentage content of the polysaccharide is 30% to 0%; the mass percentage content of the polyvinylpyrrolidone is 30% to 0%; the mass percentage content of the carbomer is 30% to 0%.

[0016] In some embodiments of the present invention, the polysaccharide is hydroxypropyl cellulose particles, and its average particle size is 0.5 μm to 2000 μm.

[0017] In some embodiments of the present invention, the patch preparation is a tablet or a sponge.

[0018] The present invention has the following advantages over the prior art: By selecting polyethylene oxide particles with a specific molecular weight and a specific particle size, the present invention uses them to prepare a biocompatible patch preparation for promoting the repair of oral mucosal injuries. After being applied to the damaged wound surface of the oral mucosa, this preparation forms a colloid covering the damaged wound surface of the oral mucosa (such as oral ulcers, etc.), which can effectively protect the oral mucosa and promote the repair of the damaged wound surface.

[0019] The present invention will be further described in detail below in conjunction with the accompanying drawings and specific embodiments. Brief Description of the Drawings

[0020] Figure 1It is a schematic diagram of the adhesion force test used to evaluate the adhesion performance in the embodiments of the present invention;

[0021] Figure 2 It is a transmission electron micrograph of the ulcer surfaces of the experimental group and the control group of the #2 patch preparation (magnification: 5000 times);

[0022] Figure 3 It is a transmission electron micrograph of the ulcer surfaces of the experimental group and the control group of the #7 patch preparation (magnification: 5000 times). Detailed implementation manners

[0023] Next, the technical solutions of the present invention will be further elaborated in combination with the exemplary embodiments and the accompanying drawings of the present invention. Obviously, the embodiments described herein are only for illustrative purposes and do not exhaust all embodiments of the present invention. The following description of the exemplary embodiments is only illustrative and does not constitute any limitation to the protection scope of the present invention. Based on the embodiments of the present invention, all other implementation manners obtained by those of ordinary skill in the art without creative efforts fall within the protection scope of the present invention.

[0024] Unless otherwise specifically stated, the numerical values and numerical ranges recorded in the exemplary embodiments of the present invention do not constitute any limitation to the protection scope of the present invention. For the sake of brevity, the technologies and methods known to those of ordinary skill in the relevant fields are not described in detail herein, but where appropriate, the known technologies and methods should be regarded as part of this specification. In all the examples described herein, any specific value should be interpreted as merely exemplary and not constituting any limitation. Therefore, other examples except the exemplary embodiments may have different values.

[0025] Example 1

[0026] This embodiment provides four oral patch preparations #1 to #4 containing polyoxyethylene (PEO) particles with different weight average molecular weights. The physical and chemical parameters of the PEO contained in the patch preparations #1 to #4 are shown in Table 1 below.

[0027] Table 1: Physical and chemical parameters of the PEO contained in the exemplary patch preparations #1 to #4

[0028] Formulation No. PEO Physicochemical Parameters #1 Weight-average molecular weight: 1 million; Particle size: 0.5 μm to 2000 μm; #2 Weight-average molecular weight: 2 million; Particle size: 0.5 μm to 2000 μm; #3 Weight-average molecular weight: 4 million; Particle size: 0.5 μm to 2000 μm; #4 Weight-average molecular weight: 7 million; Particle size: 0.5 μm to 2000 μm;

[0029] The PEO particles contained in the patch preparations in this embodiment can be obtained through commercial channels or prepared by methods known in the art. The oral patch preparations of this embodiment are prepared according to the following steps:

[0030] (a) Select the PEO raw materials in Table 1 for tabletting.

[0031] (b) Place the selected raw materials in a tableting machine and prepare oral patch preparations #1 to #4 by tableting. The weight of each tablet is 0.16 g / tablet.

[0032] The prepared patch preparation will form a colloid covering the damaged wound surface of the oral mucosa after being applied to the damaged wound surface of the oral mucosa, which can effectively protect the oral mucosa and promote the repair of the damaged wound surface.

[0033] To evaluate the effects of the patch preparations #1 to #4 in this example on promoting the repair of damaged oral mucosa, the following method was used to test the prepared oral patch preparations #1 to #4.

[0034] 1.1 Adhesion test

[0035] The adhesion between the colloid covering the damaged wound surface of the oral mucosa formed by the patch preparation on the oral mucosa and the oral mucosa is also one of the factors for protecting the oral mucosa and promoting the repair of the damaged oral mucosa. Therefore, it is necessary to test the adhesion performance of the patch preparations #1 to #4 in this example.

[0036] 1.1.1 Test purpose:

[0037] Test the adhesion of the oral patch preparation in this example to the oral mucosa. 1.1.2 Test method:

[0038] This example uses Figure 1 the shown tester for testing. Take an ex vivo porcine oral cavity, lay its mucosal layer outwards on the robotic arms at both ends of the tester, and take one piece (0.16 g) of each of the above-prepared patch preparations #1 to #4 and attach them to the lower mucosa (about 2 cm 2 ). After about 10 seconds, it can be observed that a colloid is formed on the mucosal surface. Set the tester according to the following parameters: compression speed: 20 mm / min, switching condition: force ≤ -50 gf, pause time: 0.5 min, stretching speed: 20 mm / min, and run the tester to test the adhesion of patch preparations #1 to #4.

[0039] 1.1.3 Test results:

[0040] The adhesion test results of patch preparations #1 to #4 are shown in Table 2 below. It can be seen from Table 2 that the adhesion of the above patch preparations #1 to #4 to the oral mucosa is greater than 1 N.

[0041] Table 2 Adhesion test results of #1 - #4 patch preparations to oral mucosa

[0042] #1 #2 #3 #4 Adhesion Force (N) 1.42 1.47 1.49 1.43

[0043] 1.2 Promoting healing and mucosal protection effects of oral patch preparations

[0044] After the patch preparations #1 - #4 of this example are applied to the damaged wound surface of the oral mucosa, a colloid will be formed covering the damaged wound surface of the oral mucosa, which can effectively protect the oral mucosa and promote the repair of the damaged wound surface. Next, the effects of patch preparations #1 to #4 in promoting the repair of the damaged oral mucosa and protecting the oral mucosa are tested.

[0045] 1.2.1 Test purpose:

[0046] An experimental model is established through acetic acid-induced experimental oral ulcers in rats to detect the promoting effect of patch preparations #1 to #4 on the repair of oral ulcers.

[0047] 1.2.2 Test method:

[0048] Rats in the experimental group and the control group are anesthetized with 10% chloral hydrate. A plastic tube with an inner diameter of 0.4 cm and a length of 3 cm (one end is plugged with cotton to prevent solution leakage) is filled with 35% acetic acid solution. The end plugged with cotton is placed on the inner mucosal surface of the lower lip of the rat, and it is vertically fixed for 60 seconds. Then, a local red halo can be observed on the lower lip. After 24 hours of observation, ulcers appear, and the experimental oral ulcer model is successfully established.

[0049] In the experimental group, the drug is administered 1 hour after the ulcer is formed. The patch preparations #1 - #4 are respectively attached to the oral ulcer surfaces of the corresponding groups of rats, and the control group is not administered. After that, the patch is applied once a day, one patch each time. After 3 days, the conditions of the ulcer surfaces in each group are observed, and the ulcer area is measured.

[0050] After 3 days, the changes in the ulcer areas of each experimental group and the control group of patch preparations #1 - #4 are shown in Table 3. And, the ulcer surfaces of the experimental group and the control group using the #2 patch preparation are observed by transmission electron microscopy, and the images are as Figure 2 shown.

[0051] Table 3 Changes in ulcer areas of the experimental groups and the control group of #1 - #4 patch preparations

[0052]

[0053] As can be seen from Table 3 and Figure 2 it can be known that in this example, the patch preparations #1 to #4 can all effectively reduce the irritation and damage caused by acid solution to the oral mucosa tissue, and have a protective effect on the oral mucosa of rats. At the same time, for the already formed oral ulcer tissue, the patch preparation can effectively reduce the external irritation it receives, accelerate the healing of oral ulcers, and have a therapeutic effect on oral ulcers.

[0054] Example 2

[0055] Compared with Example 1, this example provides four patch preparations #5 to #8, which contain polysaccharides, povidone, and carbomer in addition to polyethylene oxide (PEO). Among them, the physicochemical parameters of polyethylene oxide (PEO) are: weight average molecular weight of 2 million, particle size of 0.5 μm to 2000 μm; the particle sizes of povidone, carbomer, and hydroxypropyl cellulose are about 0.5 μm to 2000 μm.

[0056] In some embodiments of the present invention, the patch preparations #5 to #8 are prepared according to the following steps:

[0057] (a) Add various raw materials according to the component mass ratios in Table 4 below and mix them evenly;

[0058] (b) Place the mixed raw materials in a tableting machine and prepare the patch preparations #5 to #8 by tableting for protecting the oral mucosa.

[0059] Table 4: Component ratios of the patch preparations #5 to #8

[0060] Formulation No. Component Mass Ratio #5 Polyethylene oxide: Hydroxypropyl cellulose = 9:1 #6 Polyethylene oxide: Polyvinylpyrrolidone = 9:1 #7 Polyethylene oxide: Carbomer = 9:1 #8 Polyethylene oxide: Hydroxypropyl cellulose: Polyvinylpyrrolidone: Carbomer = 7:1:1:1

[0061] To evaluate the effects of the patch preparations #5 to #8 in this example on promoting the repair of oral mucosa injury wounds, the following method is used to test the prepared patch preparations #5 to #8.

[0062] 2.1 Adhesion test

[0063] 2.1.1 Test purpose:

[0064] Test the adhesion of the oral mucosa patch preparations #5 to #8.

[0065] 2.1.2 Test method:

[0066] The method is the same as that described in Example 1. As Figure 1 shown, take the excised pig oral cavity, lay the mucosal layer outwards on the adhesion tester, and attach the above-prepared patch preparations #5 to #8 to the lower mucosa respectively. Set the tester according to the following parameters: compression speed: 20 mm / min, switching condition: force ≤ -50 gf, pause time: 0.5 min, tensile speed: 20 mm / min, and then start the tester to test the adhesion.

[0067] 2.1.3 Test results

[0068] The adhesion test results of the patch preparations #5 to #8 are shown in Table 5 below. After testing, the adhesion of the patch preparations #5 to #8 to the oral mucosa is greater than 1 N.

[0069] Table 5 Adhesion test results of the patch preparations #5 - #8 to the oral mucosa

[0070] #5 #6 #7 #8 Adhesion Force (N) 1.43 1.34 1.45 1.38

[0071] 2.2 Oral patch preparation promotion of healing and mucosal protection effect test

[0072] 2.2.1 Test purpose:

[0073] Using the same method as in Example 1, an experimental model was established by inducing experimental oral ulcers in rats with glacial acetic acid to detect the promoting effect of patch preparations #5 to #8 on the repair of oral ulcers. 2.2.2 Test method:

[0074] Rats in each of the experimental group and the control group were anesthetized with 10% chloral hydrate. A plastic tube with an inner diameter of 0.4 cm and a length of 3 cm (one end plugged with cotton to prevent solution leakage) was filled with 35% glacial acetic acid solution. The end plugged with cotton was placed on the inner mucosal surface of the lower lip of the rat, and it was vertically fixed for 60 seconds. It could be observed that there was a local red halo on the lower lip. After 24 hours of observation, ulcers appeared, and the model was successfully established.

[0075] In the experimental group, the drug was administered 1 hour after ulcer formation. Patch preparations #5 to #8 were respectively attached to the oral ulcers of the rats in the corresponding groups. The control group was not administered. After that, the patch was applied once a day, one patch each time. After 3 days, the conditions of the ulcer surfaces in each group were observed, and the ulcer area was measured.

[0076] After 3 days, the changes in the ulcer areas of each experimental group and the control group of patch preparations #5 - #8 are shown in Table 6. And, the ulcer surfaces of the experimental group and the control group using patch preparation #7 were observed by transmission electron microscopy, and the images are as Figure 3 shown.

[0077] Table 6 Changes in ulcer areas of experimental groups and control groups of patch preparations #5 - #8

[0078]

[0079] As can be seen from Table 6 and Figure 3 it can be known that the patch preparations #5 to #8 of this embodiment can effectively reduce the irritation and damage caused by acid solution to oral mucosal tissue and have a protective effect on rat oral mucosa. At the same time, for the already formed oral ulcer tissue, the patch preparation can effectively reduce the external irritation it receives, accelerate the healing of oral ulcers, and have a promoting effect on the repair of oral ulcers.

[0080] The present invention has been specifically described above in combination with specific embodiments. These specific embodiments are only exemplary and cannot be used to limit the protection scope of the present invention. Those skilled in the art can make various modifications, changes or substitutions to the present invention without departing from the essence and scope of the present invention. Therefore, various equivalent changes made in accordance with the present invention still fall within the scope covered by the present invention.

Claims

1. Use of polyoxyethylene particles in the preparation of a biocompatible patch preparation for promoting the repair of oral mucosal injuries, wherein: The weight-average molecular weight of the polyoxyethylene is 1 million to 7 million Daltons; The average particle size of the polyoxyethylene particles is 0.5 μm to 2000 μm; The patch preparation is configured to form a colloid covering the oral mucosal injury wound after being applied to the oral mucosal injury wound.

2. The application according to claim 1, wherein, The average particle size of the polyoxyethylene particles is 50 - 500 μm.

3. The application according to claim 1, wherein, The adhesion force of the colloid to the oral mucosa is not less than 1 N.

4. The application according to claim 1, wherein the patch preparation further comprises at least one of polysaccharide, povidone, and carbomer.

5. The application according to claim 4, wherein The patch preparation further comprises polysaccharide, and the mass ratio of polyoxyethylene to polysaccharide is 9:1 to 7:

3.

6. The application according to claim 4, wherein, The patch preparation further comprises povidone, and the mass ratio of polyoxyethylene to povidone is 9:1 to 7:

3.

7. The application according to claim 4, wherein The patch preparation further comprises carbomer, and the mass ratio of polyoxyethylene to carbomer is 9:1 to 7:

3.

8. The application according to claim 1, wherein The patch preparation comprises polysaccharide, povidone, and carbomer, and in this patch preparation, the mass percentage content of polyoxyethylene particles is 99% to 70%; the mass percentage content of polysaccharide is 30% to 0%; the mass percentage content of povidone is 30% to 0%; the mass percentage content of carbomer is 30% to 0%.

9. The application according to claim 4, wherein The polysaccharide is hydroxypropyl cellulose particles, and its average particle size is 0.5 μm to 2000 μm.

10. The application according to claim 4, wherein the patch preparation is a tablet or a sponge.

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