Assistant of the Tashkent Pharmaceutical Institute, Uzbekistan, Tashkent
JUSTIFICATION OF THE COMPOSITION OF A POLYMER FILM OBTAINED ON THE BASIS OF MEDICINAL PLANT RAW MATERIALS AND CHLORHEXIDINE
ABSTRACT
This article presents the results of studies on the selection of the optimal film-forming polymer for the production of dental films of complex composition containing chlorhexidine biguconate and hemostat extract are presented. Liquid extract hemostat is obtained from local plant materials (Urtica dioica L., Polygonum hydropiper L., Polygonum aviculare L.) and is used in medical practice as a drug that has a hemostatic and anti-inflammatory effect. In particular, based on experiments, the necessary polymer auxiliary substance for the formation of phytofilms was selected and its moderate concentration of the plasticizer glycerol in the polymer mass was justified. The experiments were carried out using one of the methods of mathematical planning (Latin square 3x3).
АННОТАЦИЯ
Приведены результаты исследований по выбору оптимального плёнкообразующего полимера для получения стоматологических плёнок сложного состава, содержащих хлоргексидина бигюконата и экстракт гемостата. Жидкий экстракт гемостат получают на основе местного растительного сырья (горца перечного, горца птичьего и крапива) и применяют в медицинской практике как препарат, обладающий кровоостанавливающим и противовоспалительным действием. В частности, на основе экспериментов выбрано необходимое полимерное вспомогательное вещество для формирования фитоплёнок и обоснована его умеренная концентрация пластификатора глицерина в полимерной массе. Эксперименты проводились с использованием одного из методов математического планирования (латинский квадрат 3х3).
Keywords: medicinal plants, hemostat liquid extract, chlorhexidine bigluconate, sodium carboxymethylcellulose, plasticizer glycerin.
Ключевые слова: лекарственные растения, кровоостанавливающий жидкий экстракт, хлоргексидина биглюконат, карбоксиметилцеллюлоза натрия, пластификатор глицерин.
Introduction. The use of medicinal herbs as medicine is one of the most ancient directions, the history of which begins with the formation of man. The peoples of ancient Greece, China, Arabia, Central Asia and Western Europe used medicinal plants instead of medicine. Development of medicinal products using medicinal plants, study of their pharmacological properties, and application of effective, harmless drug forms to medical practice is one of the important tasks, and a number of studies are being conducted in this direction [1-4].
Nowadays, the demand for modern medicines based on medicinal plant raw materials is increasing. Application of convenient forms of drugs, especially in the field of dentistry, is one of the urgent issues of today. One of the promising directions for the development of modern therapy for the treatment and prevention of early caries is the search for drugs that ensure the uniform release of bioactive substances and provide the necessary therapeutic concentration of drugs with gradual absorption. Depending on the method of use of the drug form - as a drug form, the field of application has been expanded, they are intended for use in dermatology, eye and oral cavity. Currently, the creation of active substances in the form of medicinal veils is one of the urgent issues of modern pharmaceutical technology. The effectiveness of the use of medicinal substances in the form of polymer curtains is confirmed by the results of a number of studies [5-6].
Synthetic antibacterial drugs are mainly used for the treatment of oral cavity diseases. However, in recent years, the interest of dentists in their use has decreased sharply, for example, this is a significant decrease in immunity, digestive function disorders both local and general, the development of dysbacteriosis, allergic reactions and other diseases. In this regard, herbal preparations are preferred in the treatment of dental diseases. Phytopreparations contain complex biologically active substances and have a number of advantages: good tolerance, safety, high efficiency, and are explained by the fact that they show a wide range of therapeutic effects. In recent years, a lot of attention has been paid to the technology of phytopreparations, a modern drug form based on phytopreparations [7,10,11, 12].
Based on this, it can be concluded that the development of the technology of polymer curtains, i.e. phytocurtains, based on extractive preparations from plants is one of the urgent issues.
It has been confirmed that the liquid extract of "Hemostat" obtained on the basis of local raw materials has a hemostatic, anti-inflammatory, capillary strengthening effect [4]. Chlorhexidine bigluconate can be mentioned among medicinal substances with various antiseptic and antimicrobial effects that are widely used in dental practice. Taking into account the multifaceted pharmacological properties of "Hemostat" liquid extract, the urgency of developing the technology of complex dental phytoplankton together with chlorhexidine bigluconate was justified.
The purpose of the research is to develop a moderate composition of herbal preparations containing "Hemostat" liquid extract and chlorhexidine bigluconate based on local medicinal plant raw materials.
Materials and methods: in the experiments "Hemostat" liquid extract (FS 42-Uz-1249-2016) and meeting the requirements of the European Pharmacopoeia (European Pharmacopoeia 8thEdition): methylcellulose (MTs) [01/2014:0345], polyvinylpyrrolidone (PVP) [07 /2011:0685).] sodium-carboxymethylcellulose (Na-KMTs)-European Pharmacopoeia 3rd Edition – 1997:0472.- P.547-548, film-forming polymers such as gelatin [SPh X., 331], and glycerin as a plasticizer - FSP 42 Uz-29399767-2020 was used.
In the assessment of the quality of phytopards obtained during the study, the RF State Pharmacopoeia [8]. (14th edition of 2018 PPA 1.4.1.0035.18), State Pharmacopoeia of the Republic of Uzbekistan [9]. and the methods presented in the literature were used: appearance, pH index (using the potentiometric method), melting time [13-16].
The first step in the development of the technology of phytoscreens is to justify the concentration of active components in the polymer mass. Therefore, in order to justify the amount of "Hemostat" liquid extract and chlorhexidine bigluconate contained in phytoscreens, model polymer masses were prepared.
In the researches, the amount of "Hemostat" liquid extract is in the range of 5-7.5%, the concentration of chlorhexidine bigluconate is in the range of 0.02-0.04%, and the parameters of the formed phytoplankton were studied.
Based on the results of determining the physical and mechanical parameters of phytopards made from studied model polymer masses and the recommendations of pharmacologists, the amount of "Hemostat" liquid extract and 0.02% of chlorhexidine in the polymer mass was set as moderate for obtaining phytopards. One of the important issues in the creation of phytoscreen technology is the choice of an auxiliary polymer that forms a moderate screen.
For this purpose, various film-forming polymers: methylcellulose (MTs), sodium-carboxymethylcellulose (sodium-KMTs), polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVS), gelatin were studied. The studied compositions are presented in Table 1
Table 1.
The studied compositions of hemostat liquid extract and chlorhexidine bigluconate-preserving model polymer masses based on different polymers
Components, g |
The amount of components per 100 g of curtain mass, g |
||||
content 1 |
content 2 |
content 3 |
content 4 |
content 5 |
|
"Hemostat" liquid extract |
5,0 |
5,0 |
5,0 |
5,0 |
5,0 |
Chlorhexidine bigluconate |
0,02 |
0,02 |
0,02 |
0,02 |
0,02 |
sodium-KMTs |
2,0 |
|
|
|
|
MTs |
|
2,0 |
|
|
|
Gelatin |
|
|
10,0 |
|
|
PVS |
|
|
|
10,0 |
|
PVP |
|
|
|
|
10,0 |
Glycerin |
2,0 |
2,0 |
2,0 |
2,0 |
2,0 |
Purified water |
up to 100 |
up to 100 |
up to 100 |
up to 100 |
up to 100 |
Polymeric membranes were obtained by the melting method known in the literature. For this, when obtaining model polymer masses, a solution of the appropriate polymer is first taken, then chlorhexidine bigluconate dissolved in water, "Hemostat" liquid extract and plasticizer glycerin are added to it. The resulting polymer mass is homogenized for 25-30 minutes using a MM3M magnetic mixer. Ready polymer masses are poured into special molds and dried at 30℃.
Physico-mechanical parameters of the formed phytoplanks were studied. In this case, the appearance of polymer curtains, melting time, migration from molds, average weight, pH indicator were determined using MH and methods presented in the literature. The obtained results are presented in Table 2.
According to the results of the experiment, it was found that the indicators of the dental curtains obtained from the studied polymers are different. The best results in terms of appearance were observed in phytoscreens obtained from sodium-KMTs and PVS-based polymers. Only PVP and PVS curtains showed negative results regarding mold release properties.
Table 2.
The results of determining the physical and mechanical parameters of phytoscreens prepared on the basis of liquid extract of "Hemostat" in different polymers
Learned indicators |
Contents |
||||
1 |
2 |
3 |
4 |
5 |
|
External appearance |
Curtains are elastic, smooth, pale yellow |
Curtains are elastic, smooth, pale yellow, deformable met |
Curtains are fragile, smooth, brown in color |
Curtains are elastic, smooth, pale yellow |
Veins are very fragile, fragile, pale yellow |
The feature of moving out of the mold |
The curtains came off the mold easily |
The curtains came off the mold easily |
The curtains came off the mold easily |
Curtains were difficult to move from the mold |
It is difficult to remove the curtains from the mold |
Average weight, g |
0,283 |
0,390 |
1,25 |
1,45 |
1,05 |
Melting time, minutes |
22 |
40 |
14 |
5 |
10 |
рН indicator |
6,5 |
5,75 |
4,7 |
6,09 |
4,82 |
But positive results in terms of elasticity and uniformity were observed in phytoscreens obtained using sodium-KMTs polymer. Based on the obtained experimental results, sodium-KMTs were selected as a moderate polymer for the formation of phytoscreens.
At the next stage of research, it was based on the moderate concentration of sodium-KMTs and plasticizer glycerin in the polymer mass forming phytoscreens.
To achieve the goal, the experiments were performed according to the mathematical planning method, that is, the 3x3 derivative square plan [16]. The following factors were studied: factor A - Na-KMTs polymer concentration;
Factor V is the concentration of glycerol in the polymer mass.
The levels of the studied factors are presented in Table 3.
During the experiments, polymer masses containing different concentrations of sodium-KMTs and glycerol were prepared by the method described above. The following quality indicators of the formed phytoscreens were studied as moderation parameters: the ability to move from the mold - Y1; melting time -Y2; рN indicator Y3;
The ability of phytopards to move from the mold was evaluated in a 3-point system: 1 point - phytopards that moved from the mold with difficulty or did not move at all; 2 points - curtains moved from the mold; 3. Phytoparadises are very easily transferred from the mold.
Table 3.
The investigated concentrations of polymer and plasticizer in the polymer mass forming the dental phytopard containing "Hemostat" liquid extract and chlorhexidine bigluconate.
factor |
factor levels |
A – polymer concentration of Na-KMTs |
а1 – 1 %; а2 - 2,0%; а3 - 2,5% |
B- plasticizer glycerin concentration |
b1-1%; b2-2% b3-3% |
Table 4 shows the planning matrix of the parallel experiments and the results of determining phytoplankton indicators.
Table 4.
Planning matrix and moderation parameters of experiments on the basis of moderate concentration of polymer and plasticizer in phytoplankton
The number of experiments |
Factors studied |
Indicators and results studied |
|||
А |
В |
Y3- the ability to move from the mold |
Y2– dissolution time, minutes |
Y1–pH indicator |
|
1 |
а1 |
b1 |
0 |
20 |
5,54 |
2 |
а1 |
b2 |
0 |
25 |
5,85 |
3 |
а1 |
b3 |
0 |
30 |
5,71 |
4 |
а2 |
b1 |
2 |
35 |
6,05 |
5 |
а2 |
b2 |
3 |
39 |
6,03 |
6 |
а2 |
b3 |
3 |
44 |
6,03 |
7 |
а3 |
b1 |
2 |
53 |
6,07 |
8 |
а3 |
b2 |
2 |
65 |
6,1 |
9 |
а3 |
b3 |
3 |
75 |
6,07 |
In order to have clear conclusions about the results of the experiment, the moderation indicators (Y1,Y2,Y3) were combined into one general indicator. For this, the generalized propensity function was used, and with the help of this function, the quality indicators of phytoplankton were transferred to the propensity function indicators. A special propensity scale was created according to the obtained indicators.
Figure 1 shows the propensity scale and generalized propensity function of parameters such as mold migration ability (Y1), dissolution time (Y2) and pH index (Y3) of "Hemostat" liquid extract and chlorhexidine bigluconate preserving phytopars.
According to the experimental results, the Y1, Y2, Y3 parameters were transferred to the generalized propensity function - D according to the following equation:
The results of the experiment are presented in Table 5. According to the statistical analysis of the obtained results, a range of moderate compatibility of the studied factors was determined. The order of moderate compatibility with respect to polymer concentration (factor A) was a2 > a3 > a1. The order of compatibility in terms of glycerol concentration (B factor) was as follows: b2>b1>b3.
Figure 1. Propensity function of moderation parameters such as mold migration ability (Y1), melting time (Y2) and pH index (Y3) of "Hemostat" liquid extract and chlorhexidine bigluconate preserving phytofilms
Table 5.
Values of phytoscreens prepared on the basis of "Hemostat" liquid extract and chlorhexidine transferred to the propensity function
The number of experience |
Indicators of the propensity function |
general indicators of the propensity function |
||
d1 |
d2 |
d3 |
||
1 |
0 |
0,808 |
0,458 |
0 |
2 |
0 |
0,725 |
0,299 |
0 |
3 |
0 |
0,608 |
0,342 |
0 |
4 |
0,5 |
0,5 |
0,767 |
0,5769 |
5 |
1 |
0,367 |
0,758 |
0,6526 |
6 |
1 |
0,258 |
0,758 |
0,5799 |
7 |
0,5 |
0,142 |
0,775 |
0,3803 |
8 |
0,5 |
0,075 |
0,799 |
0,3104 |
9 |
1 |
0,016 |
0,775 |
0,2315 |
Based on the above results, it was determined that the moderate concentration of sodium-KMTs in the polymer mass is 2,0%, and the plasticizer (glycerin) is 2% for the development of the technology of dental phytopards containing the liquid extract of "Hemostat" and chlorhexidine.
Conclusions. According to the experimental results, a suitable polymer "moderate film forming" was selected for obtaining dental phytoscreens containing liquid extract of "Hemostat" and chlorhexidine. Moderate concentration of selected polymer-sodium-KMTs and plasticizer glycerol in the polymer mass was based. In this case, the experiments were performed on the basis of the mathematical planning method - the Latin 3x3 square matrix. The obtained results showed that the concentration of 2.0% sodium-KMTs and 2.0% glycerol was chosen as moderate in the polymer mass.
References:
- 1.Saydalieva, F., Fayzieva, Z., Azimova, B., Normakhamatov, N. Study of specific properties of Polygonum Aviculare L. dry extract as a hemostatic agent, 2022, Journal of Pharmaceutical Negative Results, 13(4), pp. 1176-1180.
- 2.Abdurakhmanova N.A., Ibragimov A.Y., Ganiev A.K., Mezhlumyan L.G., Yuldasheva N.K. Amino-acid and lipid compositions of gelrem preparation. Chemistry of Natural Compounds, 2010, 46, 4, pp. 669 - 670
- 3.Rakhimova E., E., Madrakhimov Sh. N., Gulyamova D. R. "The Form of Ointment Drug and its Role in the Pharmaceutical Market of Uzbekistan." Central Asian Journal of Medical and Natural Science 4.1 (2023): 276-282.
- Yunuskhodzhaeva N.A., Saydalieva F.A., Kazantseva D.S. Hemostatic properties of a collection from medicinal plants of knotweed, peppermint and nettle” // “Infection, immunity and pharmacology”2012.- №4.- P.76-79.
- Nazarova Z.A., Tureeva G.M., Faizullaeva N.S., Khusenova Sh.Sh. Determination of bioavailability and pharmacological activity of application dosage forms// Science Time. 2019. №3 (63). URL: https://cyberleninka.ru/article/n/opredelenie-biologicheskoy-dostupnosti farmakologicheskoy-aktivnos
- Tureeva G.M., Madaminova M. Optimization of the composition of dental medicinal films containing lincomycin and sea buckthorn oil //Science Time. 2018. №1 (49). URL: https://cyberleninka.ru/article/n/optimizatsiya-sostava-stomatologicheskih-lekarstvennyh plyonok-soderzhaschih-linkomitsin-i-oblepihovoe-maslo
- Tureeva G.M., Gaipova N.N. Development of the optimal composition of dermatological medicinal films with liquid extract from nettle leaves and calendula flowers //Science Time. 2016. №11 (35). URL: https://cyberleninka.ru/article/n/razrabotka-optimalnogo-sostava dermatologicheskih-lekarstvennyh-plyonok-s-zhidkim-ekstraktom-iz-listiev-krapivy
- State Pharmacopoeia of the Russian Federation. – 14th ed., M.: 2018., OFS.1.4.1.0035.18. - Films 3262p. Electronic resource: http://www.femb.ru/femb/pharmacopea.php
- State Pharmacopoeia of the Republic of Uzbekistan, 2021, 1st edition, volume 1, part 1.-1214-p
- Tureeva G.M., Yunuskhodzhaeva N.A., Zoirova M.A. Technologies of medicinal phytofilms based on knotweed tincture, rationale for optimal composition //Eurasian Journal of Medical and Natural Sciences»-2023.- Vol.3, Issue 4.- p.- 21–29. https://in-аcademy.uz/index.php/EJMNS/article/view/11894.
- Kasenov K.J. Phytoplenki - achievement and perspective application in modern medicine // Clinical medicine of Kazakhstan. 2012. T. 24, No. 1. P. 104-107.
- Alekseeva I.V., Solovyova K.L., Veselkova T.A. Development of composition, technology and quality assessment of phytofilms based on dry plant extracts // Modern problems of science and education. – 2012. – № 5 URL: https://science-education.ru/ru/article/view?id=7174
- Golovanenko A.L., Smirnova M.M., Alekseeva I.V., Blinova O.A. Basic approaches to the standardization of medicinal films//Modern problems of science and education.–2012.– № 2.- URL: https://science-education.ru/ru/article/view?id=5694
- Losenkova S.O., Morozov V.G., Losenkov V.P., Evseev A.V., Gladkaya Yu.V. Assortment of dosage forms used in dental practice // Bulletin of the Smolensk State Medical Academy 2019.-Т.18.-№ 4.-P. 229-237.
- Groshovy T.A., Markova E.V., Golovkin V.A. Mathematical planning of experiments in pharmaceutical technology. Plan designs. Kyiv: Higher. school, 1992. 187 p.