CN112245411A

CN112245411A - Universal oral bandage and preparation method thereof

Info

Publication number: CN112245411A
Application number: CN202011107371.1A
Authority: CN
Inventors: 洪筠; 李宗泰; 陈坤壹; 赵天宇
Original assignee: ORAL SUBSIDIARY SUN YAT-SEN UNIVERSITY HOSPITAL
Current assignee: ORAL SUBSIDIARY SUN YAT-SEN UNIVERSITY HOSPITAL
Priority date: 2020-10-16
Filing date: 2020-10-16
Publication date: 2021-01-22
Anticipated expiration: 2040-10-16
Also published as: CN112245411B

Abstract

The invention provides an oral bandage, which comprises a fixing layer and an isolating layer which are sequentially attached, wherein the fixing layer comprises a hydrophobic surface and an adhesive surface; the isolating layer is provided with a drug carrier. The oral bandage can be directly applied to ulcer affected parts, can relieve pain, promote wound healing and shorten the course of disease, has no side effect and strong adhesive force, can be firmly and durably applied to the oral ulcer affected parts, is not easy to fall off when a patient eats or drinks water, and reduces the stimulation to the oral ulcer affected parts when the patient eats or drinks water.

Description

Universal oral bandage and preparation method thereof

Technical Field

The invention belongs to the technical field of medicines, and particularly relates to a universal oral bandage and a preparation method thereof.

Background

The oral cavity is the environment outside the teeth, and has the main functions of secreting saliva and serving as a place for food intake to stay, chew and swallow. Meanwhile, microorganisms symbiotic with hosts exist in the oral cavity, and form a tiny ecosystem with the oral environment. Under normal physiological conditions, the micro-ecosystem in the mouth is stable and can resist the external influence on the environment. However, when there is a lesion of oral mucosa in the oral cavity, the invasion of external microbes on the wound surface will affect and slow down the healing of the lesion, even aggravate the inflammation and deterioration of the wound surface, and affect daily life.

Oral mucosa diseases refer to diseases in which the normal color, shape, integrity and function of the mucosa of a certain part of the oral cavity are changed. The lesions are of various types and can be combined into complex and various lesions, including aphthous ulcers, lichen planus, leukoplakia, pemphigus and the like. They have the common characteristics that the oral mucosa can be incomplete and functionally lost; in addition, the continuous activity of the oral cavity, the continuous invasion of external factors such as food and the like, the invasion of microorganisms in the oral cavity, the erosion of physicochemical factors such as acid-base solution and the like cause the characteristics of high difficulty and long time for healing the lesion of the oral mucosa, and bring great trouble to the daily work and life of patients.

There is also a dilemma with the treatment of oral mucosal diseases. Research shows that the composition is suitable for local treatment of skin diseases and oral mucosa diseases. However, due to the complex oral environment, the existence of physicochemical factors such as continuous oral movement, saliva and digestive juice, biological factors such as microorganisms living in the mouth, and external factors such as food, the drugs cannot be fixed on the affected part of the mucous membrane in a limited manner, and are easy to be diluted and fall off, and then enter the digestive system to be absorbed by the human body, thereby generating serious side effects. The above dilemma makes the conventional topical treatment means for skin diseases not effectively applied to the oral mucosa.

The existing treatment means for oral mucosa diseases are generally systemic medication or oral local gargling. But has the following disadvantages: 1) the local drug concentration is low; 2) the medicine selection surface is narrow: many dermatological agents that have proven effective for oral mucosal diseases are currently available in dosage forms suitable for oral or topical administration to the skin; 3) the systemic administration has great side effects.

In view of the above dilemma, research teams have conducted corresponding research and development work at home and abroad, however, the existing products in the market at present cannot meet the requirements of clinical treatment. The types of oral topical preparations on the market are mainly classified into the following types: oral cavity sticking film, oral cavity sticking film and oral cavity film glue. (1) The existing oral sticking film is composed of hydroxypropyl methylcellulose, can be adhered to an oral lesion part transiently, but has water solubility, is easy to dissolve by saliva and is easy to be influenced by oral movement, the adhered part is not firm, and the action time is not lasting. (2) Although the existing oral patch can be firmly adhered to an oral lesion, after the patch absorbs water and swells, oral foreign matters are obviously raised and are easily influenced by oral movement, drinking water and eating; in addition, the commercially available oral patch has a small area, and cannot play an effective protection role on large-area lesions. (3) Although the existing oral cavity membrane glue can effectively protect the oral cavity wound surface, has a large action area and can adapt to the more complicated oral cavity wound surface, the existing oral cavity membrane glue needs to be assisted by an ethanol solution when in use, and the ethanol solution of the oral cavity membrane glue needs to be adhered to the wound surface in the use process, so that stimulation is easily brought to the wound surface of a patient, and the adaptability of the patient is reduced. (4) The preparations on the market are developed aiming at the single lesion of 'oral ulcer', the medicines contained in the preparations are only effective to the 'oral ulcer', the treatment effect on diseases such as oral mucosa infection, mucosa injury, lichen planus and the like is not achieved, and the problem that the oral local medicine is difficult to take is not really solved; and has the problems of poor fixation, narrow drug selection range, incapability of adjusting the action area according to the wound surface and the like.

Therefore, there is a need to develop a universal oral local drug preparation, which can carry different drugs, can be firmly adhered to the affected part or the wound surface of the oral mucosa disease, is not easily affected by the oral environment and the motion, has strong adhesion, can adjust the action range according to different oral wound surfaces, and improves the comfort of the patient.

Disclosure of Invention

The invention aims to overcome the defects, provides the oral bandage which can be directly applied to an ulcer affected part, can relieve pain, promote wound healing and shorten the course of disease, has no side effect and strong adhesive force, can be firmly and durably applied to the oral ulcer affected part, is not easy to fall off when a patient eats or drinks water, and reduces the stimulation to the oral ulcer affected part when the patient eats or drinks water; in addition, the invention also provides a preparation method of the oral film.

In order to achieve the purpose, the first aspect of the invention provides the following technical scheme that the oral bandage comprises a fixing layer 1 and an isolating layer 2 which are sequentially attached, wherein the fixing layer comprises a hydrophobic surface 1-1 and an adhesive surface 1-2, the hydrophobic surface is positioned on the outer side of the bandage, and the adhesive surface is positioned on the inner side; the isolating layer 2 is provided with a drug carrier 2-1. The oral bandage is designed in two layers, and is simple in structure and convenient to use; the hydrophobic surface of the fixing layer provides mechanical and chemical protection for the affected part, and the adhesive surface of the fixing layer is used for attaching the bandage to the affected part; the drug carrier is used for attaching the drug to the wound and treating the ulcer.

Preferably, the adhesive surface is prepared by adopting a polyhydroxy compound material. The present invention selects a polyol as a material for development of an adhesive surface because of the hydrogen bonding forces of the hydroxyl groups to bond with water molecules in the oral environment to provide adhesion.

Preferably, the polyol comprises gum arabic or hydroxypropyl methylcellulose.

The invention also provides a preparation method of the oral bandage, which comprises the following steps:

s1 preparation of the immobilization layer: preparing the modified polyol material into the adhesive surface of the fixing layer

S1 preparation of the immobilization layer: selecting the burn dressing as an isolation layer main body material, and attaching the drug carrier to the burn dressing.

Preferably, the modified polyol material in step S1 is prepared by the following method:

a: heating and dissolving a polyhydroxy compound, adding NaClO with the total amount of 3-4% of the polyhydroxy compound, reacting for 2-3 h, and keeping the pH value of a reaction system at 9;

b: adding sodium thiosulfate to terminate the reaction, filtering, and placing the obtained filtrate in a drying oven to be dried into powder to obtain an oxidized polyhydroxy compound;

c: dissolving anhydrous magnesium sulfate with a proper amount of glyoxal aqueous solution to obtain a magnesium sulfate-glyoxal solution;

d: and (c) adding the oxidized polyhydroxy compound in the step b into the magnesium sulfate-glyoxal solution in the step c, carrying out constant temperature water bath, and reacting for 30min to obtain the cross-linked modified polyhydroxy compound.

Preferably, the polyol comprises gum arabic or hydroxypropyl methylcellulose.

Preferably, the reaction time in the step a is 2 to 3 hours.

Preferably, the drying temperature in the step b is 50 ℃, and the drying time is 3-4 h.

Preferably, the concentration of glyoxal in step c is 40%.

Preferably, the temperature of the thermostatic water bath in the step d is 60 ℃.

The invention has the beneficial effects that: 1) compared with systemic medication, the medicine has low concentration in the whole body range, has relatively light side effect on the body, and is beneficial to long-term medication; 2) compared with the general medicine, the medicine has high local concentration, is beneficial to relieving symptoms; 3) compared with local gargling, the contact time of the wound surface or mucosa lesion and the like in the mouth with the medicine is greatly prolonged, and the wound surface can be recovered more quickly to achieve the treatment purpose; 4) compared with simple smearing or gargling modes, the fixation of the medicine is more stable; 5) suitable barrier layers provide mechanical protection to the local lesions of the oral mucosa.

Drawings

Fig. 1 is a schematic view of the construction of the oral bandage of the present invention.

Detailed Description

In order to more concisely and clearly demonstrate technical solutions, objects and advantages of the present invention, the following detailed description of the technical solutions of the present invention is provided with reference to specific embodiments and accompanying drawings.

Example 1

Referring to fig. 1, a universal oral bandage in this embodiment includes a fixing layer 1 and an isolating layer 2, which are sequentially attached to each other, the fixing layer includes a hydrophobic surface 1-1 and an adhesive surface 1-2, the hydrophobic surface is located on the outer side of the bandage to provide mechanical and chemical protection for an affected part, and the adhesive surface is located on the inner side to attach the bandage to the affected part; the isolation layer 2 is provided with a drug carrier 2-1 for attaching the drug to the wound.

The preparation method of the universal oral bandage of the embodiment comprises the following steps:

s1 preparation of the immobilization layer:

(1) preparation of the adhesive surface material:

cross-linked modified gum arabic:

a: dissolving 9g of Arabic gum in 20ml of water, heating to dissolve, and cooling; continuously stirring (magneton, constant temperature water bath 40 ℃), slowly adding NaClO with the total amount of 3-4% of the Arabic gum, reacting for 2-3 h, and keeping the pH of the reaction system at 9 by using NaOH;

b: adding sodium thiosulfate to terminate the reaction, taking a small amount of solution after the reaction, filtering, and drying in a drying oven at 50 ℃ for 3-4 h to obtain powdered oxide gum;

c: dissolving anhydrous magnesium sulfate (catalyst, dosage is 0.25%) with a proper amount of glyoxal aqueous solution with the concentration of 40% (cross-linking agent, dosage is 6%), and obtaining magnesium sulfate-glyoxal solution;

d: and (c) adding the oxidized gum obtained in the step (b) into the magnesium sulfate-glyoxal solution obtained in the step (c), and stirring and reacting in a thermostatic water bath at 60 ℃ for 30min to obtain the cross-linked and modified Arabic gum.

(2) Selecting a hydrophobic surface material: selecting a Polyethylene (PE) film for coating.

S2 selecting an isolation layer: selecting Polyethylene (PE) film as the main material of the isolation layer, and attaching the drug carrier to the burn dressing.

Example 2

s1 preparation of the immobilization layer:

(1) preparation of the adhesive surface material:

blending modification: arabic gum (modified) + hydroxypropyl methylcellulose

a: the procedure for the preparation of modified gum arabic in example 1 was repeated.

B: gum arabic (modified): hydroxypropyl methylcellulose ═ 8: 2, heating to dissolve, and continuously stirring (magneton, constant temperature water bath 40 ℃ C.)

Comparative example 1

The only difference between comparative example 1 and example 1 is that the gum arabic in comparative example 1 is not modified.

Comparative example 2

Comparative example 2 differs from example 1 only in that the hydroxypropyl methylcellulose in comparative example 1 has not been modified.

Test example 1 simulated adhesion and Water resistance test in an oral Environment

The oral bandages of examples 1 and 2 and comparative examples 1 and 2 were tested for adhesion and water resistance of the materials in a simulated oral environment, and the specific data were compared with the length of adhesion time, and the specific test method was as follows:

simulated saliva (Na) by hand₂HPO₄ 2.38g，KH₂PO₄0.19g, NaCl 0.8g dissolved in 1000mL water), taking a fresh and clean porcine large intestine mucous membrane with the diameter of 50mm to simulate an oral mucosa, fixing the porcine large intestine mucous membrane on a glass slide, keeping the surface of the porcine large intestine mucous membrane flat, taking a circular oral ulcer membrane with the diameter of 13mm to adhere to the porcine large intestine mucous membrane, pressing for 3min by using a 200g weight, placing for 60min after removing the weight, then placing the whole porcine large intestine mucous membrane adhered with the oral ulcer membrane into a beaker, and adding 50 g of the oral ulcer membrane into the beakerAnd (3) using mL of artificial simulated saliva, placing the beaker in a constant-temperature water bath at the temperature of (37 +/-1), observing the form change of the adhered oral ulcer membrane, and recording the time for the oral ulcer membrane to fall off from the mucous membrane of the pig large intestine, namely the in-vitro adhesion time. The test results are shown in table 1.

Table 1: in vitro adhesion time test

Test example 2 comparison of therapeutic effects

And (3) detecting cytotoxicity: the cytotoxicity of the products of the invention in the examples 1 and 2 and the products of the comparative examples 1 and 2 is detected according to the following part 5 of GB/T16886.5-2017 medical instrument biological evaluation: in vitro cytotoxicity test, in examples 1 and 2 and comparative examples 1 and 2, in vitro cytotoxicity is less than or equal to grade 2.

Solution test: the cytotoxicity of the products of examples 1 and 2 of the invention and comparative examples 1 and 2 was tested according to the biological evaluation of GB/T16886.4-2003 instruments part 4: selection of experiments with blood interaction, examples 1, 2 and comparative examples 1, 2 have a hemolysis index of 0% in direct contact with blood.

The application range is as follows: the adhesive can be continuously adhered to the ulcer surface of the oral cavity, so that the erosion of saliva and oral flora to the ulcer surface is prevented, and the effects of repairing and promoting the ulcer surface to heal are achieved.

The using method comprises the following steps: before using the products of examples 1 and 2 and comparative examples 1 and 2 of the invention, the mouth is rinsed and the water around the ulcer is wiped off, the drug-loaded layer is pasted on the affected part, and the ulcer surface is covered by the film by light pressure.

120 oral ulcer volunteers were randomly selected and divided into 4 groups of 30 persons each, the same product was used in each group, the curative effect of the test results was divided into three grades, the symptoms were significantly improved, the symptoms were relieved and the symptoms were not significantly improved, and the results are shown in table 3.

TABLE 3 therapeutic effect on oral ulcer

	Significantly improved symptoms/human	Symptom relieved/human	No apparent improvement in symptoms/human
				Example 1	21	7	2
Example 2	25	4	1
				Comparative example 1	9	13	8
Comparative example 2	11	10	9

The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.

Claims

1. An oral bandage is characterized by comprising a fixing layer and an isolating layer which are sequentially attached, wherein the fixing layer comprises a hydrophobic surface and an adhesive surface; the isolating layer is provided with a drug carrier.

2. The oral bandage of claim 1 wherein said adhesive surface is formed from a polyol material.

3. An oral bandage as recited in claim 2, wherein said polyol comprises gum arabic or hydroxypropyl methylcellulose.

4. A preparation method of an oral bandage is characterized by comprising the following steps:

5. The method of claim 4, wherein the modified polyol material of step S1 is prepared by the following method:

6. The method of claim 5, wherein the polyol comprises gum arabic or hydroxypropyl methylcellulose.

7. The method of claim 5, wherein the reaction time in step a is 2 to 3 hours.

8. The method according to claim 5, wherein the drying temperature in step b is 50 ℃ and the drying time is 3 to 4 hours.

9. The method of claim 5, wherein the concentration of glyoxal in step c is 40%.

10. The method according to claim 5, wherein the temperature of the thermostatic waterbath in the step d is 60 ℃.