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RESEARCH ON THE COMPOSITION DEVELOPMENT AND PHYTO-OINTMENT TECHNOLOGY
FOR COMPLEX MASTOPATHY THERAPY
Zuikina S.
PhD of Pharmacy
Associate Professor of Department of Pharmaceutical Technology of Drugs, NUPh
Vyshnevska L. Doctor of Pharmacy, Professor Head of Department of Pharmaceutical Technology of Drugs, NUPh
Abstract
To date, a significant part of the overall pharmaceutical market belongs to natural herbal products. Currently, about 40 % of pharmaceutical products in the world contain medicinal plant raw materials.
In order to expand the range of phytomedicines for the treatment of mastopathy, pharmacotechnological studies were conducted to develop the composition and technology of ointments based on vegetable oils for use in complex therapy of mastopathy, having hormone-regulating, wound healing, antimicrobial, reparative action.
Keywords: mastopathy, phyto-ointment, vegetable oils, technology.
Introduction. According to WHO experts, in the coming years the share of phytomedicines in total pharmaceutical consumption will reach 60 %. This is due to the fact that more than 12 % of the Earth's population has allergic reactions associated with the use of synthetic drugs.
The problem of mastopathy treatment, given the high risk of malignant neoplasms, is important and requires modern approaches to the pharmacological development of drugs used in the complex treatment of the disease [1 - 3].
Materials and methods. The aim of the work was to develop the composition and technology of combined phytomedicine for the use in complex mastopa-thy therapy. Active pharmaceutical ingredients that provide hormone-regulating, reparative, regenerative, wound healing and anti-inflammatory actions are parsley fatty oil, sea buckthorn oil, amaranth oil, tea tree oil [4, 5] (Table 1). [].
Table 1
Physical and chemical properties of components of ointment "Phytolan" for complex mastopathy therapy
Active pharmaceutical ingredient Description, physical and chemical properties Legislation
Sea buckthorn oil Oily, motionless orange-red liquid with a characteristic pleasant taste, without bitterness, and with a specific odor. It does not dry in air. A slight precipitate, which dissolves when heated to 40 ° C, is allowed. Easily soluble in chloroform, methylene chloride, petroleum ether, n-hexane, glacial acetic acid. It is slightly soluble in 95 % ethanol, practically insoluble in water SPhU 2 ed. T. 1 «Vegetable fatty oils» P. 1053 - 1055. European pharmacopoeia 6.0, Vol.1 «Vegetable fatty oils». P. 712 - 714.
Parsley seed fatty oil Viscous oily liquid of yellow-green color with a specific spicy flavor. It is slightly soluble in 95 % ethanol, practically insoluble in water SPhU 2 ed. T. 1 «Vegetable fatty oils». P. 1053 - 1055. European pharmacopoeia 6.0, Vol.1 «Vegetable fatty oils». P. 712 - 714
Amaranth oil Oily yellowish liquid with a nutty-herbaceous odor. It is slightly soluble in 95 % ethanol, practically insoluble in water SPhU 2 ed. T. 1 «Vegetable fatty oils». P. 1053 - 1055. European pharmacopoeia 6.0, Vol.1 «Vegetable fatty oils». P. 712 - 714
Tea tree oil Colorless or light yellow liquid with a specific odor with a tinge of camphor. Soluble in ethanol, vegetable oils, propylene glycol; poorly soluble in glycerol; insoluble in water International standard ISO 4730 European pharmacopoeia 6.0, Vol.1 «Essential oils». P. 680 - 682
Thanks to the proposed composition of natural plant components (vegetable oils), natural base and the optimal combination of technological properties of the dosage form, an effective drug with anti-inflammatory, antimicrobial, reparative action, which maximally promotes the penetration of medicinal substances into the skin of the breast, is obtained [6, 7].
The unique healing properties of amaranth oil are largely determined by the presence in its composition of two powerful antioxidants - squalene and vitamin E contained in amaranth oil in a rare, especially active to-cotrienol form).
Amaranth oil contains more than 70 % of mono-and polyunsaturated fatty acids (linoleic (Omega-6), oleic (Omega-9), linolenic (Omega-3), arachidonic, palmitoleic acids, etc.), more than 9 % of phospholipids (dominated by phosphatidylcholine), squalene (more than 8 %), about 2 % of vitamin E, phytosterols (more than 2 %), carotenoids (precursors of vitamin A), vitamin D, bile acids, various macro- and trace elements: potassium, iron, phosphorus, calcium, magnesium, copper etc [8].
Squalene is a valuable component of amaranth oil. Squalene began to be used in medicine for the first time in Japan. In 1955, squalene was found to have antibacterial properties and was used in the treatment of tuberculosis patients. Further studies showed that squalene is absolutely safe for humans. Moreover, a deep study of the secretion of human skin glands has shown that this substance is its component. Thus, squalene was used in the treatment of problem skin.
Human skin is open to the influence of environmental factors. A lipid film that results from mixing the secretion of the sebaceous glands with lipids performs a protective function of the skin. Squalene plays an important role in this process. It has plastic properties that ensure the integrity of the stratum corneum. It is responsible for skin elasticity, softens and moisturizes it, preventing peeling. Squalene inhibits conditionally pathogenic microorganisms, but does not violate normal microflora, has immunomodulatory and anti-inflammatory properties, protects the skin from various disorders.
Squalene is a part of the sebaceous glands and subcutaneous fat, is an important participant in the synthesis of steroid hormones, cholesterol and vitamin D in humans. Squalene contained in amaranth oil, actively contributes to the saturation of organs and tissues with oxygen, has a powerful antitumor and anticancer action, as well as greatly increases the resistance of the human body to various viral, fungal, bacterial infections and exposure to harmful radioactive. It prevents the development and spread of malignant tumors, activates the metabolic processes, promotes the rapid and effective repair of damaged areas of the skin and mucous membranes. The use of squalene stimulates skin rejuvenation, saturating it with oxygen and restoring blood supply. The process of protein synthesis increases, making the skin fresh, tight and supple. Squalene helps patients with various forms of skin diseases, activates the work of skin cells, which helps rapid wound healing. Due to the pronounced wound healing properties of squalene, amaranth oil has been widely used in folk medicine for many centuries across the world for centuries.
Vitamin E, like squalene, prevents the premature aging of the human body, promotes immunity, and in addition, has anti-inflammatory properties, lowers blood cholesterol and prevents blood clots, strengthens the walls of blood vessels, prevents arterial formation. Vitamin E, contained in amaranth oil, also helps to improve the functional state of the muscular system and plays an important role in the reproductive system of the person (participates in the processes of spermatogenesis and embryonic development, promotes the maintenance of normal hormonal balance).
The high value of amaranth oil is also determined by the polyunsaturated fatty acids that make up it. Among them, the leading position is taken by irreplaceable polyunsaturated linoleic acid (the proportion of this Omega-6 acid in the fatty acid composition of amaranth oil is more than 50 %). Linoleic acid, like other unsaturated acids in the composition of amaranth oil, promotes fat metabolism, has anti-inflammatory and immune stimulating action, improves skin condition, cardiovascular, digestive, nervous, genital and endo-
crine systems, and plays an important role in the organism of the human from slags, toxins, salts of heavy metals and other harmful substances [9].
Amaranth oil contains carotenoids, which transform in humans into fat-soluble vitamin A, which, like squalene, is involved in the synthesis of steroid hormones and largely determines the wound healing and immune stimulating action of amaranth oil. Vitamin A participates in the processes of natural synthesis of fibrillary proteins of keratin and collagen (which are structural components of skin, hair and nails), normalizes the secretion of sebaceous glands, regulates glucose content in the blood, and also plays an important role in the work of the reproductive system.
Vitamin D, which is part of amaranth oil, helps to strengthen the immune system, improves the absorption of calcium and phosphorus by the human body necessary for the formation and repair of bone tissue, and also reduces the risk of some oncological, cardiovascular, endocrine diseases.
The anti-inflammatory, bactericidal, antitumor and immunostimulatory properties of amaranth oil are also largely due to the high content of phytosterol amaranth oil in the blood, which contribute to the reduction of blood content of "bad" cholesterol, prevent the development of type II diabetes and play an important role in the human body's synthesis of vitamin D, hormones and bile acids.
Parsley contains essential oil in all parts: roots (0.1 %), seeds (2-7 %) and leaves (0.3-0.7 %). The most common is parsley seed oil, probably because of the higher concentration of aromatic substances in the seeds and, accordingly, the greater yield of oil during distillation [10].
Green parsley oil has been identified to date with about 45 components, the main of which are: - mono-terpenes (up to 80 %): alpha-pinene 17 %, beta-pinene 11.8 %, alpha-fellandrene 4.6 %, beta-fellandrene 7.8 %, limonene 2.5 %, 1,3,8-para-mentathriene; - phenolic esters: myristicin 17.7 %, apiol 2 %.
Unlike parsley seed oil, parsley leaves contain little apiol and lots of terpenes, including the unique 1,3,8-para-mentathriene, which causes the parsley's unique aroma. Due to the lower content of phenolic esters, leaf oil is safer to use and terpenes cause a more pronounced antiseptic and diuretic effects.
Parsley oil has a powerful effect on the female reproductive system: it stimulates blood flow to the pelvic region and uterine contractions, restores irregular cycle (amenorrhea), eliminates pain (dysmenorrhea), normalizes the menstrual cycle, and increases lactation. It relieves muscle tension, relieves the condition of mechanical tissue damage, bruising, reduces muscle pain, narrows blood vessels, improves local circulation, which is very important when damaged skin of the breast and nodal cells mastitis.
The composition of parsley essential oil contains natural phytoestrogens, so the product is actively used in the period of hormonal restructuring of the body: during pregnancy, puberty, and menopause. It is useful to use parsley oil for the treatment of the female genital area; it helps with scanty blood flow during menstruation. Apiol increases blood circulation, stimulates reduction of inflammation and disappearance of cysts.
Sea buckthorn oil is the richest source of the most useful for the human body substances (carotenoids, vitamins (E, C, B1, B2, B3, B6, B9, K), macro- and microelements (magnesium, iron, calcium, manganese, silicon, nickel, molybdenum, etc.), amino acids, mono-and polyunsaturated fatty acids, phytosterols, phospholipids). Sea buckthorn also contains a number of other biochemical components, which largely determine the variety of therapeutic and prophylactic use of this useful herbal product (among such substances there are fla-vonoids (rutin, isoramethine quercetin, campferol, etc.), triterpenic acids (ursolic), organic acids (tartaric, salicylic, oxalic, malic, succinic), volatiles, tannins, pectins, coumarins, etc.) [11].
The most useful in mastopathy is vitamin E, which has antioxidant and anti-cancer effects; enhances the effect of progesterone hormones on breast tissue, thereby reducing the growth of fibrous tissue in fibrocystic mastopathy; improves lipid metabolism, decreases the likelihood of weight gain when treated with hormonal drugs; removes the manifestations of premenstrual syndrome; reduces inflammatory changes in breast tissue; promotes rapid tissue regeneration by enhancing collagen formation.
Vitamin A (retinol) is a natural regulator of estrogens; it leads to the normalization of their content in excess. This leads to a decrease in the growth of epithelial tissue and stroma of the mammary gland and to a decrease in such manifestations of mastopathy as glandular swelling and tenderness. Retinol is a good anticancer; its long-term administration is able to prevent the transition of mastopathy to malignant forms.
Vitamin C stabilizes the vascular wall, prevents fluid from leaving the vessels in the breast tissues, i.e. reduces swelling and breast enlargement during mastopathy. It also performs antioxidant function, eliminating radicals and improving metabolism in the alveolar sinuses.
Vitamin P (rutin) has a vitamin C-like effect by supplementing and enhancing it, so it is often recommended to take a combination of these two elements.
Vitamin D prevents malignant degeneration of mastopathy. Vitamins of group B (B1, B2) reduce manifestations of neuroses and stress, relieve pain in mastopathy. B6 reduces the amount of pituitary synthesized prolactin, improve cardiovascular and nervous system activity.
Tea tree oil composition is determined by the international standard ISO 4730. Among the more than 98 compounds contained in the oil, terpin-4-ol is responsible for the most of the antimicrobial activity. In the composition of the oil there are such frequently met components as terpinen-4-ol, the concentration of which varies from 30 % to 48 %, and the 1,8-cineol, the concentration of which is from 0 to 15 %, and some other components.
Tea tree essential oil has an anti-inflammatory and anti-tumor (in vitro) effect [12].
Lanolin anhydrous is well absorbed into the skin and has a soothing effect. Basically it is a mixture of esters of high-molecular alcohols (cholesterol, iso-cholesterol, etc.) with higher fatty acids (myristic, palmitic, cerotic, etc.) and free high-molecular alcohols.
In terms of properties, lanolin is close to human sebum (chemical similarity to eleidin - a substance
found in the glossy layer of the epidermis). In chemical terms it is quite inert, neutral and stable during storage. The most valuable property of lanolin is its ability to emulsify up to 180-200 % (by weight) of water, up to 140 % of glycerol and about 40 % of ethanol (of 70 % concentration) with the formation of water/oil type emulsions. Additions of a small amount of lanolin to fats and hydrocarbons dramatically increase their ability to mix with water and aqueous solutions, which has led to its widespread use in lipophilic-hydrophilic bases.
Lanolin has a very high emulsifying ability, improves the absorption of ointment, promotes deeper penetration of active substances into breast tissue, promotes healing of nipple cracks and softens breast skin [1].
It is one of the most effective fats that promotes good moisturizing, softening and nourishing of the
skin. Lanolin-containing remedies help to protect the skin from adverse environmental influences.
The pronounced moisturizing properties of lanolin are due to the ability to absorb and retain a large amount of moisture. Penetrating deeply into the skin, lanolin not only saturates the skin with moisture, but also prevents its loss for a long time.
The use of lanolin allows making the skin soft and supple, and significantly increases the regeneration of its cells.
Results. Preliminary studies proved the antimicrobial activity of the developed ointment and substantiated the possibility of its use in the treatment of mechanical damages of breast tissues, prevention of mastopathy and therapy of "hospital infections" caused by staphylococcal infection, which often accompanies maternity wards.
The technological scheme of ointment production is shown in Fig. 1.
Fig. 1 Technological scheme of obtaining ointment "Phytolan'
In order to control the quality of the technological process of obtaining ointment "Phytolan", the controlled parameters and eligibility criteria were determined (Table 2).
Table 2
Controlled parameters and eligibility criteria in the manufacturing of ointment "Phytolan"
Stage Controlled parameter Eligibility criteria Measurement method
Weighing of components of a phyto-ointment Quantity of raw materials The quantity of components meets the requirements of the TPR Gravimetric
Obtaining an oil mixture The uniformity of the solution, time, temperature, mixing speed Homogeneous mixture of yellow-greenish color 20 min. 100 rpm, 15 - 25°C Chronometric, visual control, temperature indicator
Obtaining of the ointment "Phytolan" The degree of homogenization, temperature, rotation speed of the stirrers, the time of homogenization No un-emulsified oils, 15 - 25°C 45 rpm 30 min. Visual control, temperature indicator, chrono-metric control
Preparation of containers and packing materials Quantity of containers (tubes) and covers, temperature and time of drying, appearance of prepared containers (tubes) Compliance with TPR Visual control, temperature indicator, chrono-metric control
Ointment packing Deviation in the weight of the ointment, the number of filled containers, tightness of packing Deviation in mass ± 5 %, tightness of packing Weight, visual control
Marking of containers (tubes) Correctness and clarity of marking (batch number, expiry date, etc.) Compliance with the MQQ Visual control
Packaging Completeness of packaging, clarity of marking Compliance with the MQQ Visual control
Discussion. The chemical composition of phy-tooils is studied and their expediency of using in the complex scheme of mastopathy therapy is substantiated. The technological scheme of manufacturing ointment "Phytolan" is developed. In order to ensure the quality of the technological process of obtaining "Phytolan" ointment, the step-controlled parameters, eligibility criteria and methods of their measurement were determined.
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