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International Medical Scientific Journal      Issue-3 

10.5281/zenodo.5762446 

103 

  



Art of Medicine           Volume-1 

International Medical Scientific Journal      Issue-3 

10.5281/zenodo.5762446 

104 

 

 

 

Art of Medicine International Medical Scientific journal 

 

Founder and Publisher Pascual Izquierdo-Egea 

Published science may 2021 year. Issued Quarterly. 

Internet address: http://artofmedicineimsj.us 

E-mail: info@artofmedicineimsj.us 

11931 Barlow Pl Philadelphia, PA 19116, USA +1 (929) 266-0862 

 

 
  



Art of Medicine           Volume-1 

International Medical Scientific Journal      Issue-3 

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Comparative characteristics of healing of AFTHOUS stomatitis in 

experiment 

Akbarov A.N., Ziyadullaeva N.S., Irismetova B.D. 

Tashkent State Dental Institute Republic of Uzbekistan  

  

Abstract. The work is based on the results of experimental studies on the usage 

of a new form of Heprocel medication. The experiment has used outbred white rats, 

which were divided into 2 groups: control and experimental. In the experimental 

group of animals, HEPROCEL powder was applied to the surface of an artificially 

induced traumatic ulcer. The developed method for local protection of traumatic 

lesions of the oral mucosa with Heprocel made it possible to shorten the regeneration 

time of the erosive process and the period of complete regression of inflammatory 

changes. 

Keywords: Heprocel, treatment of aphthous stomatitis, regeneration of the oral 

mucosa. 

Introduction. Aphtha is a focal deep fibrinous inflammation of the oral mucosa, 

proceeding according to the Artyus phenomenon, resulting in more or less 

pronounced destruction of the epithelium, and sometimes the underlying connective 

tissue part of the mucous membrane [6, 7]. 

The application of new treatment regimens for local inflammatory appears to be 

interesting, innovative and promising. It practices manifestations in the oral cavity 

through the development of differentiated principles of therapy, taking into account 

the pathogenetic and morphological mechanisms of the erosive process of the oral 

mucosa, the characteristics of the course and development of recurrence of HRAS [1, 

2, 8, 9, 10]. However, the use of most drugs gives a short-term effect with the 

manifestation of discomfort in the form of a burning sensation and side effects, such 

as exacerbation of gastric ulcer and duodenal ulcer, leukopenia, anemia, and skin rash 

[3, 4, 5]. 

Objective of the study: experimental and morphological substantiation of the 

effectiveness of a new local method for the treatment of aphthous stomatitis. 

Material and methods. In the experiments were used 61 outbred white rats of 

different sex weighing 220-290 grams. The control group of rats included 32 

individuals, experimental 29. The animals were kept in clean, spacious cages. Rooms 

for animals are equipped with ventilation and air conditioning, constant lighting. The 

nutrition was balanced with the inclusion of a sufficient amount of proteins, 

carbohydrates, vitamins. After the ulcer formation, the animals were provided with a 

diet of non-coarse food to reduce pain. 



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106 

Daily monitoring of the condition of the animals consisted of examining the oral 

cavity, washing the area of the formed ulcer in the control group with water (2.0 ml), 

and in the experimental group, after washing with water, an implant in the form of 

HEPROCEL powder was applied with the formation of a gel on the surface of the 

ulcer. The animals were weighed. General condition, mobility, nutrition and 

physiological functions were assessed. 

All operations were carried out in accordance with the rules adopted by the 

European Convention for the Protection of Vertebrate Animals used for Experiments 

or Other Scientific Purposes (ETS N 123), Strasbourg, 03/18/1986. Removal from the 

experiment was carried out by inhalation of an increased dose of halothane vapor. 

Terms of withdrawal from the experiment: 1 hour, 12 hours, 1 day, 3, 5, 7, 14, 21, 30 

days. 

The proposed method for the formation of a chronic ulcer is as follows: a 

chronic ulcer of the oral mucosa is formed by applying filter paper circles moistened 

with 50% acetic acid to the oral mucosa, characterized in that standard 3x3 mm 

circles are applied from the side of the lower lip mucosa and fixed with a special 

holder - a clip of the appropriate size, allowing for fixation in a certain place with a 

force of 50-100 kPa, and also to prevent dilution of the concentration of the active 

agent by the separating saliva. The model of such a formation of an ulcer in the oral 

cavity in a rat makes it possible to cause a lesion with the development of a local 

aphthous lesion of the mucous membrane, which provides a more comprehensive 

study to assess the effectiveness of topical application of various agents.  

In the experimental group of animals, starting from 3 days after exposure to the 

surface of the aphthous ulcer, the powder "HEPROCEL" (finely dispersed) was 

applied with the formation of a gel due to the secretion of the salivary glands. The gel 

has good adhesion to necrotic tissues, therefore, application is sufficient for 1 minute. 

Treatment of the ulcer with a wound dressing with the formation of a gel was carried 

out daily at the same time. 

HEPROCEL is a bio-soluble, biodegradable polymer implant with hemostatic 

properties, manufactured by Turon Silk. Release form - powder. 

Physicochemical characteristics of the finished product "НEPROCEL": at t 

20°C solubility in water 10 g/l, soluble in water, insoluble in most organic solvents. 

Melting point 220°C. Stable at pH 5-7. It hydrolyzes quickly in an alkaline 

environment, more stable in an acidic environment. 

The next stage of the study was a morphological assessment of changes in the 

oral mucosa in experimental animals during the formation of an aphthous ulcer and 

the dynamic processes of its reparation. Tissue samples were fixed in 10% formalin 

solution in phosphate buffer. Paraffin sections were stained with hematoxylin and 



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107 

eosin. Light-optical micrographs were obtained with an Axioscop 40-ZEISS 

microscope, coupled with a digital camera. All micrographs were processed and data 

saved on a computer using Microsoft-Windows XP-Professional software. 

To assess the adhesion of the cover for use in the oral cavity, we took into 

account the following circumstances:  

- to determine the optimal type and consistency of the coating for better 

adhesion to the wound surface of the oral mucosa;  

- to study the adhesion and durability of the coating depending on the phases of 

wound healing;  

- to study the rate of dissolution of the coating under the conditions of washing 

with liquid or enzyme solutions. 

Results. The results of treatment in the experimental group of rats showed that 

on the 3rd day after exposure, an aphthous ulcer was detected, formed on the mucous 

membrane of the lower lip with indistinct contours, undermined edges. On the 5th 

day, treatment was started, the HEPROCEL powder was applied to the area of 

aphthous ulcer of the mucous membrane of the lower lip to form a gel on the surface 

of the ulcer (Fig. 1). On the 7th day of the experiment, the ulcer is covered with a 

fibrin film, has a fairly clear border, signs of inflammation with subsiding, 

granulation tissue is visible under the fibrin film (Fig. 2). 

 

  
Fig. 1. The experimental rats on the 

5th day of the experiment. FIELD 

mucosa of the lower lip aphthous 

ulcers coated powder 

"НEPROСEL" to form a gel on the 

Fig. 2. The experimental rats on the 

7th day of the experiment. Ulcer is 

covered with a fibrin film has 

enough clear boundary. Signs of 

inflammation from subsiding. 



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ulcer surface. Granulation tissue viewed under a 

fibrin film. 

 

At the same time, a finely dispersed powder "HEPROCEL" was again applied to 

the area of the formed aphthous ulcer with the formation of a gel on the surface of the 

ulcer (Fig. 3). On the 14th day, complete healing of the oral mucosa was determined 

after the formation of an acetate ulcer and treatment with a gel coating of cellulose 

derivatives (Fig. 4). 

 

  
Fig. 3. Experienced rat on the 7th 

day. On the region formed aphthous 

ulcer re-applied fine powder 

"НEPROСEL" to form a gel on the 

ulcer surface. 

Fig. 4. Experienced rat on the 14th 

day of treatment. Complete healing 

of the mucosa of the oral cavity after 

formation of ulcers acetate and 

treatment with the gel coating of 

cellulose derivatives. 
 

Thus, experimental studies on the formation of chronic aphthous ulcers in the 

oral cavity showed that, in the absence of specific treatment, regression of the 

inflammatory process begins only by 10-14 days of observation with complete 

epithelialization by 30 days, in turn, the local application of the powder form of the 

drug "HEPROCEL" with the subsequent formation of a gel on the surface of the ulcer 

already 2 days after the start of therapy (on the 7th day of the experiment) leads to the 

activation of the reparative process with the formation of granulation tissue under the 

fibrin film and complete healing of the mucous membrane by 14 days. 

Analysis of histological changes during the formation and healing of 

experimental aphthous ulcers in rats showed that 12 hours after the start of the 



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109 

experiment, it was determined that the stratified squamous epithelium was thinned, 

the mucous membrane was degraded, the lamina propria was edematous with 

elements of necrosis, the muscle layer was edematous with degradation, the glands 

were numerous (fig. 5). 

After 36 hours, degradation of the epidermis and stratified squamous epithelium 

was already noted, the lamina propria was with necrotic masses, the glands were 

degraded, the striated muscles were edematous and dissociated (Fig. 6). 

On the third day, the same pattern persisted (Fig. 7). Further, in the control 

group of animals, the healing process was characterized by the following picture on 

the 5th day. The stratified squamous epithelium was eroded in places, the epidermis 

was altered, the papillae were smoothed, the mucous membrane with elements of 

degradation and necrosis, the lamina propria is edematous with elements of necrosis, 

the muscle layer is edematous with degradation, and few glands are degraded. In 

dynamics, on the 7th day, an actually equivalent picture was determined (Fig. 8).  

  

Fig. 5. Micrograph of an 

aphthous ulcer of the oral 

mucosa in rats - 12 hours 

Fig. 6. Micrograph of aphthous 

ulcer of the oral mucosa in rats, 

36 hours 

 

  



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Fig. 7. Micrograph of aphthous 

ulcer of the oral mucosa in rats on 

the 3rd day of the experiment. 

Fig. 8. Micrograph of the rat lip 

mucosa in the control group of 

animals: the beginning of the 

healing process on the 7th day 

 

On the 14th day, signs of the onset of regression of the inflammatory process 

were determined, the epidermis was modified, the papillae were high, the stratified 

squamous epithelium was edematous, the mucous membrane with elements of 

degradation and necrosis, the lamina propria edematous with elements of necrosis, 

the muscle layer was edematous with degradation, the glands were numerous 

degraded (Fig. 9). 

On the 21st day, cleansing of necrotic masses was noted, but signs of edema of 

the epithelium, fibroelastic and muscle tissue, and the glands were partially degraded 

(Fig. 10). 

By the 30th day, complete restoration of the structure of the tissues of the 

mucous membrane, the absence of signs of degradation, the glands are numerous, the 

vessels with blood filling. 

  

Fig. 9. Micrograph of the rat lip 

mucosa in the control group: the 

healing process on the 14th day. 

Fig. 10. Micrograph of the mucous 

membrane of the lip of a rat in the 

control group of animals: the 

healing process on day 21 

 

In the main group of animals in the study of the morphology of the proposed 

interaction with the coating surface of the wound in the space between them is 

marked formation of thrombotic masses. In the experimental group animals 1 day 

after exposure of the powder surface aphthous ulcers "НEPROСEL" formed film 

adheres to the wound surface. The epithelial layer is composed of stratified squamous 

epithelium, which places thinned, the epidermis is modified, papillae smoothed 



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mucosa with elements degradation and necrosis, lamina propria of the mucosa with 

edematous necrosis elements muscular layer edematous with degradation few gland 

degraded (Fig. 11). 

Subsequently on day 7 of the experiment and 2 hours after application of the 

powder "НEPROСEL" morphological pattern of interaction with the surface of the 

ulcer GPRS characterized in that the formed film is subjected to fragmentation in the 

abutment zone defined clusters of blood cells. High epithelium, lamina propria 

mucosa forms a high papillae, striated muscle slightly swollen in the submucosa 

mucosal side lips are numerous glands, ducts their associated with the mucosal 

surface. There was a significant reduction in signs of inflammation, necrotic changes 

actually determined (Fig. 12). 

  

Fig. 11. Micrograph of the mucous 

lip of the rat in the experimental 

group of animals: 1 day after 

exposure to the surface of the 

aphthous ulcer of the powder 

"НEPROCEL" 

Fig. 12. Micrograph of the mucous 

lip of the rat in the experimental 

group of animals: on the 7th day 

after exposure to the surface of the 

aphthous ulcer of the powder 

"HEPROCEL" 

 

  



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Fig. 13. Micrograph of the mucous 

lip of the rat in the experimental 

group of animals: on the 14th day 

after exposure to the surface of the 

aphthous ulcer of the powder 

"HEPROCEL" 

Fig. 14. Micrograph of the mucous 

membrane of the rat lip in the 

experimental group of animals: on 

the 21st day after exposure to the 

surface of the aphthous ulcer of the 

powder "HEPROCEL" 

 

On the 14th day after exposure to the surface of the aphthous ulcer of the 

powder "HEPROCEL", only small areas were determined after the fragmentation of 

the applied coating. The epithelial layer consists of stratified squamous epithelium, 

the lamina propria forms papillae, the striated muscles are slightly edematous, 

numerous glands are located in the submucosa of the mucous part of the lip, their 

excretory ducts are lined with stratified squamous epithelium and are connected to 

the mucosal surface. There are no phenomena of degradation, necrosis and 

inflammation, complete repair of the ulcer. (fig. 13). 

On the 21st day after exposure to the surface of the aphthous ulcer of the 

"HEPROCEL" powder, only unchanged tissue was determined. Complete repair of 

the ulcer (Fig. 14). 

Аnalyzes and discussions. Thus, the model of the formation of an aphthous 

ulcer of the oral mucosa in rats according to our modified method allows the 

formation of a chronic ulcer of the mucous membrane in the area of the lower lip and 

gums. Already 20 minutes after exposure, you can trace visual changes in the mucous 

membrane in the form of darkening of tissue color and edema. After 3 hours, the 

affected area has a dark color and clearly differs from the surrounding healthy tissue. 

After 12 hours, an ulcerative necrotic crater forms on the surface of the mucosa with 

necrotic tissues and detritus along the periphery of the ulcer. After 1 day, the formed 

mucosal defect has undermined edges with necrotic plaque and tissue edema. Starting 

from 3 days after exposure, the ulcer looks like a chronic one, covered with fibrin, the 

edges are edematous, distinct. There are no signs of granulation. In the control group 

of animals, the healing process is delayed up to 3 weeks with a gradual rejection of 

necrotic masses, the formation of a fibrin film and epithelialization starting from the 

edges of the ulcer. Complete healing of the ulcer can be traced to 30 days after 

exposure. In the experimental group of animals, the research results showed that the 

gel on the surface of the ulcer visually lasts for 2-3 hours, then covers the ulcer in the 

form of a transparent, barely perceptible thin film tightly adhered to the surface of the 

ulcer, a faster relief of the inflammatory process with epithelization of the surface is 

noted ulcers within 2 weeks of exposure. 



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Conclusions. Comparative studies of various forms of the domestic drug 

"НEPROCEL" with the formation of a gel coating on the surface of a chronic 

aphthous ulcer of the oral mucosa in rats showed that, depending on the phase of the 

wound process, the fixation resistance and the strength of the gel structure change, 

with the best performance achieved when using fine powder in phase of necrotic 

changes. 

The study of the morphological features of the interaction of the proposed 

coating with the wound surface of the oral mucosa showed that the HEPROCEL 

powder has a good adhesive ability, adheres tightly to the wound surface, a decrease 

in the inflammatory process and the beginning of repair is noted already from the 

second day after application with complete restoration of signs of degradation of cell 

structures and regression their edema and necrosis by 14 days of the experiment and, 

accordingly, 7 days of treatment. 

The developed method of local protection of aphthous lesions of the oral mucosa 

in conjunction with a systemic approach to the treatment of stomatitis made it 

possible to shorten the regeneration time of the erosive process and the period of 

complete regression of inflammatory changes. 

 

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