CN112245411B

CN112245411B - Universal oral bandage and preparation method thereof

Info

Publication number: CN112245411B
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: 2023-06-16
Anticipated expiration: 2040-10-16
Also published as: CN112245411A

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 hydrophobic surface is positioned at the outer side of the bandage, and the adhesive surface is positioned at the inner side; the isolating layer is provided with a drug carrier. The oral bandage can be directly applied to an ulcer affected part, can relieve pain, promote wound healing, shorten the course of disease, has no side effect and strong adhesive force, can be firmly and permanently applied to the oral ulcer affected part, is not easy to fall off when a patient takes food or drinks water, and reduces the stimulation to the oral ulcer affected part when the patient takes food 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 an external environment of teeth, and has the main functions of secreting saliva and serving as a place for food intake from the outside, such as retention, chewing and swallowing. Meanwhile, microorganisms which are symbiotic with a host exist in the oral cavity, and a tiny ecological system is formed by the microorganisms and the oral environment. Under normal physiological conditions, the micro-ecosystem in the oral cavity is stable and can resist the influence of the outside on the environment. However, when there is an oral mucosa lesion in the oral cavity, the wound surface is affected by external microorganisms, which slows down the healing of the lesion, and even aggravates the inflammation and deterioration of the wound surface, which affects the daily life.

The oral mucosa disease refers to a disease in which the normal color, appearance, integrity, function and the like of a mucosa at a certain part of an oral cavity are changed. Lesions are of a wide variety and can be combined into a complex and diverse lesion including aphtha, lichen planus, white spots, pemphigus, etc. Their common characteristics are that they may cause incomplete oral mucosa and lack of functionality; in addition, the continuous invasion of external factors such as continuous movement of the oral cavity, food and the like, invasion of microorganisms in the oral cavity, and erosion of physical and chemical factors such as acid-base solution and the like lead to the characteristics of high healing difficulty and long time of the lesion of the oral mucosa, and bring great trouble to the daily work and life of patients.

And there is also a dilemma in the treatment of oral mucosal diseases. Research shows that the composition is suitable for local treatment medicine of skin diseases and is also suitable for oral mucosa lesions. However, due to the complex oral environment, physical and chemical factors such as continuous movement of the oral cavity, saliva, digestive juice and the like, biological factors such as resident microorganisms and the like, and external factors such as food and the like exist, the medicine cannot be fixed at the mucous membrane lesion, is easy to dilute and fall off, and further enters the digestive system to be absorbed by the human body, so that serious side effects are generated. The above dilemma makes the conventional topical treatment for skin diseases ineffective for application to the oral mucosa.

The existing treatment means of oral mucosa diseases are mainly systemic administration 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 demonstrating efficacy against oral mucosal disorders, currently only in dosage forms suitable for oral or topical application to the skin; 3) Has great side effect when being used for the whole body.

Aiming at the dilemma, research and development work is carried out by research teams at home and abroad, however, the existing products on the market at present can not meet the requirements of clinical treatment. The types of oral topical preparations on the market are mainly divided into the following types: oral cavity film, oral cavity patch, oral cavity film glue. (1) The existing oral patch consists of hypromellose, and the preparation can be temporarily adhered to the affected part of the oral cavity, but has water solubility, is easily dissolved by saliva and is easily affected by oral movement, the adhered part is not firm, and the action time is not durable. (2) The existing oral patch can be firmly adhered to an affected part of an oral lesion, but after the patch absorbs water and swells, the protrusion of foreign matters in the oral cavity is obvious and is easily influenced by oral movement, drinking water and eating; in addition, the commercial oral patch has small area and cannot play an effective role in protecting a large-area lesion. (3) The existing oral cavity film glue can effectively protect the oral cavity wound surface, has a large acting area and can adapt to the complicated oral cavity wound surface, but needs an ethanol solution for assistance when in use, and the ethanol solution of the oral cavity film glue is required to be adhered to the wound surface in the use process, so that the wound surface of a patient is easy to be stimulated, and the adaptability of the patient is reduced. (4) The preparations on the market are developed aiming at the single lesion of oral ulcer, and the medicines contained in the preparations are effective only for the oral ulcer, have no treatment effect on diseases such as oral mucosa infection, mucosa injury, lichen planus and the like, and do not really solve the problem of difficult oral local administration; and has the problems of poor fixation, narrow medicine selection surface, incapability of adjusting the acting area according to wound surfaces, and the like.

Therefore, development of a general oral topical pharmaceutical preparation is needed, which can bear different drugs, can be firmly adhered to affected parts or wound surfaces of oral mucosa diseases, is not easily affected by oral environment and movement, has strong adhesion, can adjust the action range according to different oral wound surfaces, and improves the use comfort of patients.

Disclosure of Invention

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

In order to achieve the above purpose, according to a first aspect of the present invention, there is provided a technical scheme that an oral bandage comprises a fixing layer 1 and an isolating layer 2 which are sequentially laminated, wherein the fixing layer comprises a hydrophobic surface 1-1 and an adhesive surface 1-2, the hydrophobic surface is located at the outer side of the bandage, and the adhesive surface is located at the inner side; the isolating layer 2 is provided with a drug carrier 2-1. The oral bandage is of a two-layer design, is simple in structure and is 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 binding belt to the affected part; the drug carrier is used for attaching the drug to the wound and treating ulcer.

Preferably, the adhesive surface is made of a polyol material. The polyhydroxy compound is selected as a development material for the adhesive surface in the present invention because the hydrogen bonding forces of the hydroxyl groups to water molecules in the oral environment provide adhesion.

Preferably, the polyhydroxy compound comprises acacia or hydroxypropyl methylcellulose.

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

s1, preparing a fixed layer: preparation of modified polyol material into adhesive surface of fixing layer

S1, preparing a fixed layer: selecting burn dressing as main material of isolation layer, and attaching drug carrier to the burn dressing.

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

a: heating and dissolving polyhydroxy compound, adding NaClO accounting for 3% -4% of the polyhydroxy compound, reacting for 2-3 hours, and keeping the pH of the reaction system to be 9;

b: adding sodium thiosulfate to terminate the reaction, filtering, and drying the obtained filtrate in a drying oven to obtain oxidized polyhydroxy compound;

c: dissolving anhydrous magnesium sulfate with proper amount of glyoxal water solution to obtain 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, and carrying out a constant-temperature water bath for reaction for 30min to obtain the crosslinking modified polyhydroxy compound.

Preferably, the reaction time in the step a is 2-3 h.

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

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

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

The beneficial effects of the invention are as follows: 1) Compared with systemic administration, the drug concentration in the whole body range is low, the side effect on the body is relatively light, and the long-term administration is facilitated; 2) Compared with systemic administration, the local concentration of the medicine is high, which is beneficial to relieving symptoms; 3) Compared with local gargle, the contact time between the wound surface in the mouth or mucous membrane lesion and the like and 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 fixing of the medicine is more stable; 5) Suitable barrier layers provide mechanical protection against localized lesions of the oral mucosa.

Drawings

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

Detailed Description

In order to more clearly demonstrate the technical scheme, objects and advantages of the present invention, the technical scheme of the present invention is described in detail below with reference to the specific embodiments and the 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 sequentially attached to each other, where the fixing layer includes a hydrophobic surface 1-1 and an adhesive surface 1-2, the hydrophobic surface is located at the outer side of the bandage and provides mechanical and chemical protection for an affected part, and the adhesive surface is located at the inner side and is used for attaching the bandage to the affected part; the isolating 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, preparing a fixed layer:

(1) Preparation of adhesive surface material:

crosslinking modified acacia:

a: 9g of Arabic gum is dissolved in 20ml of water, heated and dissolved, and cooled; continuously stirring (magneton, constant-temperature water bath 40 ℃), slowly adding NaClO accounting for 3% -4% of the total amount of the Arabic gum, reacting for 2-3 hours, and keeping the pH of a reaction system to be 9 by 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 hours until the solution is powdery to obtain the oxidized gelatin;

c: dissolving anhydrous magnesium sulfate (catalyst, dosage of 0.25%) with 40% glyoxal water solution (cross-linking agent, dosage of 6%) to obtain magnesium sulfate-glyoxal solution;

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

(2) And (3) selecting a water-repellent surface material: and selecting a Polyethylene (PE) film for coating.

S2, selecting an isolation layer: polyethylene (PE) film is selected as the main material of the isolating layer, and the drug carrier is attached to the burn dressing.

Example 2

s1, preparing a fixed layer:

(1) Preparation of adhesive surface material:

blending modification: acacia (modified) +hydroxypropyl methylcellulose

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

B: acacia (modified): hydroxypropyl methylcellulose = 8:2, heating and dissolving, 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 has not been modified.

Comparative example 2

The only difference between comparative example 2 and example 1 is that the hydroxypropyl methylcellulose in comparative example 1 was not modified.

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

The oral bandages of examples 1 and 2 and comparative examples 1 and 2 were tested for adhesion and water resistance in simulated oral environments, and specific data were compared for the duration of adhesion, as follows:

artificial saliva (Na) ₂ HPO ₄ 2.38g，KH ₂ PO ₄ 0.19g, naCl 0.8g dissolved in 1000mL water), the fresh and clean pig large intestine mucous membrane is used for simulating oral mucous membrane, the pig large intestine mucous membrane with the diameter of 50mm is taken and fixed on a glass slide, the surface of the pig large intestine mucous membrane is kept flat, a circular oral ulcer membrane with the diameter of 13mm is taken to be adhered on the pig large intestine mucous membrane, a 200g weight is used for pressing for 3min, the weight is removed and placed for 60min, then the whole pig large intestine mucous membrane attached with the oral ulcer membrane is placed into a beaker, 50mL of artificial simulated saliva is added into the beaker, the beaker is placed into a constant temperature water bath kettle with the temperature of 37+/-1 ℃, the morphological change of the adhered oral ulcer membrane is observed, and the time when the oral ulcer membrane falls off from the pig large intestine mucous membrane is recorded, 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 Effect

Cytotoxicity detection: cytotoxicity assays were performed on the products of inventive examples 1, 2 and comparative examples 1, 2 according to section 5 of the medical device biological evaluation of GB/T16886.5-2017: in vitro cytotoxicity test (in vitro cytotoxicity of examples 1 and 2 and comparative examples 1 and 2. Ltoreq.2).

Solution test: cytotoxicity assays were performed on the products of inventive examples 1, 2 and comparative examples 1, 2 according to section 4 of the medical device biological evaluation of GB/T16886.4-2003: test selection for interaction with blood examples 1 and 2 and comparative examples 1 and 2 were directly contacted with blood with hemolysis index of 0%.

The application range is as follows: the adhesive can be continuously adhered to the dental ulcer wound surface to block the erosion of dental saliva and dental flora to the dental ulcer wound surface, thereby playing the roles of repairing and promoting the healing of the dental ulcer wound surface.

The using method comprises the following steps: before using the products of the invention of the examples 1 and 2 and the comparative examples 1 and 2, the user needs to rinse the mouth and dry the water around the ulcer, the medicine carrying layer is stuck to the affected part, and the sticking film is pressed lightly to cover the ulcer surface.

120 canker volunteers were randomly selected, and were randomly divided into 4 groups of 30 persons each, each group was treated with the same product, and the results of the test were classified into three classes, with significantly improved symptoms, with remission and insignificant improvement, and the results are shown in table 3.

TABLE 3 treatment of canker sore effect

	Obvious symptom improvement/person	Symptom relief/person	Symptom improvement is not obvious/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 examples illustrate only a few embodiments of the invention, which are described in detail and are not to be construed as limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.

Claims

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

the adhesive surface is prepared from a polyhydroxy compound material; the polyhydroxy compound is modified acacia;

the preparation method of the oral bandage comprises the following steps:

s1, preparing a fixed layer: preparing the modified polyhydroxy compound material into an adhesive surface of the fixed layer;

s2, preparing an isolation layer: selecting a polyethylene film as a main material of the isolation layer, and attaching a drug carrier to the burn dressing;

the modified Arabic gum is prepared by the following method:

a: 9g of Arabic gum is dissolved in 20ml of water, heated and dissolved, naClO accounting for 3% -4% of the total Arabic gum is added, the reaction time is 2-3 hours, and the pH value of a reaction system is kept to be 9;

b: adding sodium thiosulfate to terminate the reaction, filtering, and drying the obtained filtrate in a drying oven to obtain oxidized acacia;

c: dissolving anhydrous magnesium sulfate by using 40% glyoxal aqueous solution, wherein the dosage of glyoxal crosslinking agent is 6% by mass percent, and the dosage of magnesium sulfate catalyst is 0.25% by mass percent, thus obtaining magnesium sulfate-glyoxal solution;

d: and c, adding the oxidized Arabic gum 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 modified Arabic gum.

2. A method of preparing an oral bandage according to claim 1, comprising the steps of:

s2, preparing an isolation layer: polyethylene film is selected as the main material of the isolating layer, and the drug carrier is attached to the burn dressing.