Anti-acne oil-in-water nanoemulsion using tea tree oil, willow bark extract, and niacinamide

Abstract

In the present invention, a vegetable nanoemulsion of tea tree oil in water and enriched with willow bark extract and niacinamide has been formulated. This nanoemulsion has antibacterial properties against acne-causing bacteria (Cotibacterium acnes) and has a watery and light texture. Also, it does not leave an oily layer on the skin upon topical application. The resulting nanoemulsion is formulated without the use of common industrial and commercial emulsifiers used in the manufacture of commercial lotions, such as various derivatives of stearic acid, polysorbates, and cetyl alcohol. Therefore, it has a higher compatibility with the principles of green chemistry and green and organic hygiene products. The simplicity of the emulsifier system and its high compatibility with tea tree oil have made it unnecessary to spend high energy in the manufacture of the resulting nanoemulsion through the use of high shear force equipment or advanced systems. As a result, it can be produced more easily, at lower cost, and with simpler equipment.

Description

Description of the invention Title of the invention (as stated in the declaration) Anti-acne oil-in-water nanoemulsion using tea tree oil, willow bark extract, and niacinamide Technical background of the relevant invention The technical field of the invention is related to health products for treating acne and inflammatory pimples. The lotion made in this invention, with a special formulation consisting of tea tree oil, willow bark extract and niacinamide, can cleanse the skin and reduce the effects of acne by eliminating acne-causing bacteria (Cutibacterium acnes). Also, using tea tree oil as an active anti-acne ingredient allows the use of medicinal plants in the manufacture of health products. Technical problem and stating the objectives of the invention Acne is a skin problem that affects a wide range of people at some point in their lives. Research has shown that acne, in addition to affecting people's beauty, also affects them psychologically, including reduced self-confidence, depression, and reduced social interaction. Therefore, its prevention and treatment play an effective role in people's quality of life. Depending on its severity, acne can be treated in two ways, including the use of oral medications or topical lotions. Among them, the use of lotions has a higher level of acceptance among people in society. Acne control hygiene lotions are often based on an active chemical ingredient. Examples of these ingredients include benzoyl peroxide, retinol, and isotretinoin. One of the problems with using these ingredients, in addition to their effectiveness, is the presence of numerous side effects, which are especially common in sensitive skin prone to acne. These effects include dry skin, sensitivity to sunlight, inflammation, redness, and darkening or the formation of spots.In this case, the treated individuals must take many precautions over a relatively long period of time (duration of treatment) to maintain the efficacy and effectiveness of topical lotions, which is often unpleasant and inconvenient for consumers. In addition, retinoids, including retinol, adapalene, and isotretinoin, which are effective compounds in controlling and treating acne, have severe and harmful side effects on the fetus. Retinol, as a prodrug of retinoic acid, alters the expression of genes involved in keratinocyte proliferation, differentiation and apoptosis by binding to nuclear retinoic receptors. This potent mechanism can be completely inappropriate in skin with a weakened defense barrier, such as those with rosacea, atopic dermatitis or active psoriasis. Retinol significantly increases oxidative stress at the cellular level by increasing the skin's sensitivity to ultraviolet radiation. This not only increases the risk of sunburn, but can also lead to the formation of free radicals and damage to keratinocyte DNA. Teratology studies have placed vitamin A derivatives, including retinol, in category X during pregnancy and lactation. This means that the risk of its use clearly outweighs the benefit, as these compounds have a strong teratogenic potential. For this reason, it is recommended that pregnant women or women who may become pregnant should strictly avoid its topical use. As a systemic retinoid, isotretinoin has a profound effect on the differentiation and proliferation of sebaceous cells and keratinocytes by modulating several cellular signaling pathways, including retinoic acid receptors (RARs and RXRs). These powerful effects produce extensive systemic side effects that make its use inappropriate for many patients. The most important of these is its very strong teratogenicity, which makes its use absolutely prohibited during pregnancy. Even a short-term dose during pregnancy can cause severe abnormalities in the central nervous system, cardiovascular system, and craniofacial system of the fetus. Teratology studies have placed adapalene in category C of drugs during pregnancy. Although its systemic absorption is low, its use during this period is generally inappropriate due to its molecular similarity to teratogenic retinoid compounds (such as isotretinoin). Another example of the side effects of anti-acne compounds is benzoyl peroxide. Benzoyl peroxide, which is marketed as 5% lotions, is one of the old acne control solutions, and a significant range of its consumers require the use of a secondary moisturizer to eliminate the effects of dryness, itching, and peeling caused by this substance. These negative effects are undesirable criteria for choosing them during the treatment period. Benzoyl peroxide is a strong oxidizing agent that exerts its main mechanism of action through the production of oxygen free radicals and the oxidation of the bacteria "Cotibacterium acnes". This powerful oxidizing property can be very inappropriate for sensitive skin or skin with impaired protective barrier. This substance not only kills bacteria, but can also damage the lipids and proteins of the extracellular matrix in the stratum corneum. This damage leads to significant moisture loss, disruption of the skin barrier integrity, and increased inflammation, which clinically manifests as severe dryness, redness, and a feeling of tightness.Additionally, the strong oxidizing properties of benzoyl peroxide make it a powerful bleaching agent for fabrics and hair. Therefore, direct contact with clothing or fabrics should be avoided when using it. Antibiotics such as clindamycin and tetracycline are other effective agents in the treatment of inflammatory acne, which can be used topically depending on the severity of the acne. The most concerning aspect of the use of topical antibiotics is their potential to induce antibiotic resistance and cause secondary infections. Prolonged or irregular use of these agents disrupts the natural bacterial flora of the skin, providing a breeding ground for resistant overgrowth. The main purpose of creating this invention is to create an oil-in-water nanoemulsion with anti-acne properties, anti-acne bacteria (Cotibacterium acnes). The creation of this nanoemulsion is based on herbal ingredients including tea tree oil and willow tree extract, which is enriched with niacinamide. Tea tree oil, with the scientific name Melaleuca alternifolia, is a native plant of Australia, whose inhibitory and killing effects against the bacteria "Cotibacterium acnes" have been proven by research and scientific references. Other objectives of this invention include the following: 1- Using tea tree oil in a water-based formulation as a nanoemulsion with the aim of reducing the oily feeling while maintaining its inhibitory and killing power against Cutibacterium acnes. 2- Formulating a plant-based nanoemulsion using a plant-based emulsifying agent (decyl glucoside) 3- Formulating a plant-based oil-in-water nanoemulsion with anti-acne properties that is consistent with the principles of green chemistry and green and organic toiletries. 4- Using the benefits of willow bark extract and a stable derivative of vitamin B3 (niacinamide) to improve the performance of tea tree oil on the skin A description of the state of the prior art and the history of developments related to the claimed invention. In the patent number CN113230172B in 2021, registered by Zhuanzhou Daxun Biotechnology Co., Ltd., a lotion in the field of health and pharmaceutical materials consisting of a plant oil containing terpenes is designed for topical use. In this invention, it is claimed that the designed lotion, due to its richness in terpenes, has the properties of preventing acne scar formation, promoting skin wound healing, preventing acne, whitening, reducing skin wrinkles, and combating aging. In this invention, one of the plant oils rich in terpenes used is tea tree oil, which is used in the formulation of the lotion. In patent number US20160228482A1 filed in 2016 by Zena Pharm, a specially formulated combination is used as a carrier for tea tree oil, with the aim of improving the quality and appearance of the skin, especially in conditions where the skin suffers from conditions such as basal cell carcinoma and actinic keratosis. In this invention, tea tree oil is used as a therapeutic agent and a combination of water, propylene glycol, phenoxyethanol, heavy paraffin oil, light white paraffin, cetostearyl alcohol, and macrogol cetostearyl ether is used as a carrier. In patent number CN105536031A filed in 2016 by Jia Shumin, a dressing with anti-inflammatory and antibacterial properties is prepared using liposomes containing tea tree oil. According to the inventor, making liposomes from tea tree oil solves the problem of oil stability in the aqueous phase, allowing it to be slowly released onto the skin, extending the time of action, and providing antibacterial and anti-inflammatory properties. In the patent number CN114601797A in 2022, registered by Yangzhou University, a nanoemulsion of tea tree oil with antibacterial properties against Staphylococcus aureus bacteria is made. The lotion made in this invention contains the following ingredients with the following weight percentages: 5-10% tea tree oil, 5-8% polysorbate, 0.05-0.2% preservative and deionized water. The nanoemulsion made in this invention is of the oil-in-water type and the size of its emulsions is in the range of 20-200 nm. In the patent number CN116650557A, registered in 2023 by Zhuhai Jinbiao Biotechnology and Guangdong Simita Biotechnology, a mixture of 0.1-10 mass parts of tea tree oil, 0.1-10 mass parts of emulsifying agent, and 0.1-5 mass parts of stable emulsion hydrogel with antibacterial and anti-inflammatory properties was prepared through a high-pressure homogenization process. The emulsion prepared in this invention can be effectively used in the manufacture of sanitary and medical dressings. In the patent number WO2025058574A1, registered in 2025 by the Alpina Institute under the title "Topical composition for the treatment of acne", a mixture of Moringa and Willow extracts with a relative composition of 2:1 and 4:1 is made. In this invention, the following ingredients are used in the formulation of the topical lotion. Inutec SL-1 compound, which is a combination of inulin, dodecyl carbamate and glycerin. Glycerin monostearate as an emulsifier, cetyl alcohol and stearyl alcohol as thickeners, short chain triglycerides and Teqactive compound as a moisturizer, ethylhexylglycerin and phenoxyethanol as preservatives. Olive oil has also been used as a fragrance agent. HYPERLINK "http: / / www.uspto.gov / patents / process / search / index.jsp"HYPERLINK "http: / / www.uspto.gov / patents / process / search / index.jsp" Providing a solution to an existing technical problem along with an accurate, sufficient, and integrated description of the invention The present invention is an oil-in-water nanoemulsion consisting of tea tree oil, willow bark extract, niacinamide, glycerin, decyl glucoside, ethylhexyl glycerin, phenoxyethanol, xanthan gum, citric acid, and purified water. In this nanoemulsion, the concentration of each component is proportional to the values ​​presented in Table 1. Function of oil-in-water nanoemulsion components Tea tree oil Tea tree oil, which is distilled from the leaves of the Australian native tree Melaleuca alternifolia, is a powerful natural ingredient with broad-spectrum antimicrobial properties. The oil is best known for its ability to fight bacteria, fungi, and viruses. Its action on the skin is largely due to the presence of the active compound terpinen-4-ol, which breaks down the cell walls of microorganisms and prevents them from growing and multiplying. This mechanism is the basis for most of the therapeutic properties of tea tree oil for the skin. Tea tree oil’s most important and well-known skin benefit is its ability to treat and manage acne. It effectively reduces the redness, size, and number of pimples by killing acne-causing bacteria and reducing inflammation. Clinical studies have shown that tea tree oil can be almost as effective as benzoyl peroxide in treating mild to moderate acne, but with fewer side effects, such as dryness and irritation. This makes it a popular, natural option for acne sufferers. In addition to acne, tea tree oil is also used for other skin problems due to its antifungal and antiseptic properties. It can be effective in treating conditions such as seborrheic dermatitis (dandruff), athlete's foot, and fungal nails. It also helps relieve itching and redness caused by insect bites or dermatitis due to its anti-inflammatory properties. Willow bark extract Used in traditional medicine for centuries, willow bark extract is one of the natural treasures in the world of skincare. The key active ingredient in this extract is salicin, which is converted into salicylic acid in the body. While its strength may be milder than synthetic salicylic acid, this makes it an ideal option for sensitive skin or those who can’t tolerate stronger formulas. This compound belongs to the beta-hydroxy acid family and is known for its unique ability to dissolve oil and penetrate deep into the skin’s pores. Its main function is to gently exfoliate and break down the adhesions between dead skin cells, resulting in a brighter, smoother appearance. This extract is a very effective option for acne-prone and oily skin due to its inherent anti-inflammatory and antibacterial properties, and by penetrating into pores, it helps dissolve and clear comedones (blackheads and whiteheads) and prevents new ones from forming. Unlike many synthetic exfoliating acids, willow bark extract is often gentler and less likely to irritate the skin. This makes it a great herbal alternative for those with sensitive skin. In addition to treating acne, willow bark extract is also a powerful antioxidant due to its significant amounts of polyphenolic compounds, such as flavonoids. These compounds help neutralize free radicals caused by UV rays and pollution, preventing premature skin aging. The extract also helps maintain skin firmness and elasticity by reducing the production of enzymes that break down collagen and elastin, and in the long term, can improve the appearance of fine lines and wrinkles. Niacinamide Niacinamide, also known as vitamin B3, is one of the most effective and versatile active ingredients in skincare formulations, especially for those with acne-prone and oily skin. Unlike some acids and retinoids, this water-soluble compound is generally well-tolerated by the skin and is suitable even for sensitive skin. Its main function in this regard is to reduce sebum production and inhibit inflammation, two key factors in the development and exacerbation of acne. By regulating the activity of the sebaceous glands, niacinamide helps to mattify the appearance of the skin and reduce excessive shine. In addition to controlling oil, niacinamide simultaneously strengthens the skin’s protective barrier. By improving the synthesis of ceramides and other essential lipids, this compound makes the skin more resistant to moisture loss and external irritants. This is crucial for oily skin, which often suffers from dehydration and sensitivity in addition to excess oiliness. Also, by inhibiting the transfer of melanin to the surface layers of the skin, this vitamin helps to fade dark spots caused by acne inflammation, resulting in smoother and brighter skin. Niacinamide has significant anti-inflammatory properties that directly affect cell signaling pathways. This compound can inhibit the production of pro-inflammatory cytokines, which leads to a reduction in the redness and size of inflammatory acne lesions such as papules and pustules. On the other hand, niacinamide acts as a precursor for the vital coenzymes NAD (nicotinamide adenine dinucleotide) and NADP. These coenzymes play a key role in cellular metabolic processes for energy production and DNA repair. By supporting these processes, niacinamide helps repair and maintain the overall health of skin cells, increasing their ability to regenerate and protect themselves from daily damage. Decyl glucoside Decyl glucoside is a non-ionic emulsifying agent derived from natural and renewable resources such as sugarcane and coconut. Its main function is to create a stable and uniform emulsion by reducing the interfacial tension between the water and oil phases in lotion formulations. Its unique molecular structure, consisting of a hydrophobic fatty acid portion and a hydrophilic glucose portion, allows it to effectively adhere to the surface of oil droplets and prevent them from separating. This property is the basis for the formation of the light and desirable texture of lotions. One of the biggest advantages of decyl glucoside is its extreme mildness and skin compatibility. Not only does this emulsifier not irritate the skin, but it is also suitable for very sensitive skin and even newborn skin. Unlike many traditional emulsifiers that may weaken the skin barrier, decyl glucoside helps maintain the integrity of the skin's protective barrier. In addition, it has mild moisturizing properties that help to increase hydration and leave the skin feeling soft after applying the lotion. Another outstanding advantage of decyl glucoside is its ability to create light, silky emulsions that spread easily on the skin and are absorbed without feeling greasy or heavy. From a formulation perspective, it is compatible with a wide range of different raw materials, including active ingredients and electrolytes, and provides good thermal and physical stability to the product. Also, due to its plant origin and high biodegradability, it is an excellent choice for green, natural and environmentally friendly formulations. Glycerin Glycerin, also known as glycerol, is a powerful, safe, and widely used humectant in the world of skincare. Unlike many complex ingredients, its function is simple yet highly effective. Glycerin is a powerful humectant, meaning its molecules keep skin moisturized by absorbing moisture from the air and also drawing water from deeper layers of the skin to its surface. This not only directly increases moisture, but also fills the spaces between skin cells, strengthening the skin barrier and preventing further moisture loss. One of the most prominent properties of glycerin is its ability to repair and protect the skin’s natural barrier. By increasing the synthesis of lipids in the skin and acting as an intercellular cement, glycerin helps restore the integrity of this vital barrier. This property makes glycerin not only a moisturizer, but also a key restorative ingredient in products for very dry, damaged and sensitive skin. In addition to its deep moisturizing properties, glycerin also has emollient and protective properties. It creates a thin, non-blocking layer on the skin, making it instantly soft and supple. It also helps to improve the appearance of fine lines and wrinkles and increase skin elasticity by keeping the skin moisturized. Due to its unparalleled compatibility, gentleness, and non-allergenicity, glycerin is a constant staple in a wide range of products, from gentle cleansers to rich creams and hydrating serums, and is suitable for almost all skin types, even the most sensitive. Xanthan gum Xanthan gum is a natural and highly efficient biopolymer obtained through the fermentation of sugar by the bacterium "Xanthomonoscompetris". This natural process makes it a completely plant-based material suitable for natural and green formulations. The main function of xanthan gum in products is to create viscosity and a gel-like texture. Even at very low concentrations, it can convert dilute solutions into a stable gel. Its unique molecular structure allows it to form a three-dimensional network in the presence of water, which traps liquid and creates a uniform texture. One of the biggest advantages of xanthan gum is its excellent thermal and chemical stability. Unlike many natural thickeners that may be sensitive to heat or pH changes, xanthan gum remains completely stable over a wide range of temperatures and pH (3 to 10). This feature makes the product easy to process and increases its shelf life. Another outstanding advantage of xanthan gum is its pleasant sensory feel on the skin. Gels formed with this substance have a silky and light texture that spreads easily and is absorbed without causing stickiness or a heavy feeling. Finally, due to its natural origin, non-allergenicity and gentleness, its use is completely common and safe in all care products, from products for sensitive skin to organic formulations. Process for producing vegetable oil-in-water nanoemulsion The process of producing a vegetable oil-in-water nanoemulsion is presented in Figure 1. As can be seen, first a certain amount of decyl glucoside is dissolved in pure water and its pH is adjusted by gradually adding citric acid in the range of 4.5-6.5. Then the solution is stirred at a speed of 400 rpm. Tea tree oil is slowly added to it to create a nanoemulsion of tea tree oil. In the next step, willow bark extract is added to it to obtain a stable solution of nanoemulsions of tea tree oil and willow bark extract. In the next step, niacinamide is added to enrich the nanoemulsion with active pharmaceutical ingredients. The resulting mixture is stirred vigorously until the niacinamide is completely dissolved. Then glycerin, ethylhexylglycerin and phenoxyethanol are added to the resulting solution. In this step, a natural gelling agent xanthan gum is used to increase the viscosity of the solution and facilitate its distribution on the skin. Since the xanthan gum gelation process takes time, stirring is continued at 400 rpm until the xanthan gum gel is completely and uniformly dispersed in the solution.Finally, to ensure safety, the pH of the gelled oil-in-water nanoemulsion is determined. The pH of the mixture should be in the range of 4.5-6.5 to have acceptable skin compatibility. Dynamic light scattering analysis To confirm the formation of tea tree oil nanoemulsion in water, dynamic light scattering (DLS) experiment was used. The results of this experiment are presented in Figure 2. According to the results, the resulting nanoemulsion has only one peak with particle distribution in the range of 8-33 nm with a Z-Average of 18.6 nm. The PI coefficient value is 0.182, which indicates that the formulated nanoemulsion has acceptable uniformity. Transmission electron microscopic analysis To reconfirm the successful formation of a nanoemulsion of tea tree oil in water, powerful transmission electron microscopic analysis was used. Figure 3 shows the images of the formulated nanoemulsion at two different magnifications. As can be seen, the particle distribution is in the nanometer size range (less than 100 nm) and is in agreement with the results of dynamic light scattering (DLS) analysis. Analysis of the growth inhibition zone of Cutibacterium acnes To investigate the anti-acne properties of the formulated nanoemulsion, a test to determine the diameter of the zone of inhibition of Cutibacterium acnes (ATCC 11827) was conducted using the Well diffusion method. In this test, 1% clindamycin antibiotic was used as a reference. The results of the zone of inhibition analysis are presented in Table 2. The obtained data show that the formulated nanoemulsion has acceptable efficacy compared to the antibiotic clindamycin, which is commercially used in the treatment and improvement of acne. Explanation of shapes, maps and diagrams Figure 1) Laboratory process for producing vegetable oil-in-water nanoemulsion Figure 2) Results from dynamic light scattering (DLS) analysis Figure 3) Transmission electron microscope images at two different magnifications. Figure 4) Image of the result of the analysis of the growth inhibition zone of Cutibacterium acnes acnes (ATCC 11827), (1): Formulated herbal nanoemulsion, (2): 1% clindamycin solution, (3) sterile pure water (control sample) Table 1) Chemical formula of vegetable oil-in-water nanoemulsion with anti-acne properties Table 2) Results of the analysis of the growth inhibition zone of Cutibacterium acones bacteria A clear and precise statement of the advantages of the claimed invention over prior inventions. The use of oil-in-water nanoemulsions to provide the unique properties of oily plant materials to the skin and its industrialization is accompanied by two major limitations. The first limitation is the appropriate selection of the emulsifying agent that can achieve a nanoemulsion of uniform size and small size without using large amounts of it. For systems based on vegetable oils, this process is more difficult due to the lack of information about the HLB data of vegetable oils. Also, if it is necessary to maintain the vegetable-based formulation, the range of emulsifier selection will often be limited. The second limitation is the need to use expensive equipment to obtain nanoemulsions. Processes that often require high shear force systems or ultrasound waves that also have high energy consumption. In the present invention, a nanoemulsion with an average emulsion size of 18.6 nm has been prepared from tea tree oil in water and a plant-based formulation in which the antibacterial properties of tea tree oil against Cutibacterium acnes bacteria have been preserved. This has been achieved by increasing the effectiveness of active ingredients due to the reduction of particle size in the nanometer scale. The participation of tea tree oil in nanometer dimensions in the form of a nanoemulsion in the aqueous phase has resulted in the synthetic nanoemulsion lacking the usual heavy feeling of the oil phase on the skin and being more compatible with the skin. Also, its special formulation consisting of three main ingredients tea tree oil, willow bark extract and niacinamide, in addition to combating acne, can moisturize and heal skin damaged by acne. In this invention, the plant-based emulsifying agent decyl glucoside has been used in the selection of the agent for creating the nanoemulsion of tea tree oil in water, which is a green alternative to the commercially available emulsifying agents used in the formulations of previous inventions. The compatibility of the emulsifying agent (decyl glucoside) with tea tree oil through the selection of the optimal concentration and its inherent nature has resulted in the need for less energy and cost in creating the nanoemulsion and this nanoemulsion can be produced with only one plant-based emulsifying agent using conventional shear force mixers, which greatly reduces the need for advanced industrial systems. Reducing the concentration and number of emulsifying agents to one, along with its green nature, reduces the possibility of irritation of the final formulation on the skin, which plays a key role in improving its acceptability by consumers. Compared to previous inventions, the presented formulation uses a minimum of industrially derived chemicals, which, in addition to maintaining its effectiveness, is in more complete compliance with the culture of green chemistry and green and organic hygiene products, which improves the health and well-being of society by replacing hygiene products containing hazardous chemicals. Description of at least one implementation method for implementing the invention Before topical application of the formulated nanoemulsion, it is recommended to wash the affected area with lukewarm water or a suitable detergent to increase its effectiveness. Apply a certain amount of it on the skin and spread it gently until completely absorbed. Since the antioxidants in tea tree oil are sensitive to light, it is recommended to store the gel in a suitable container and away from direct sunlight. Explicit mention of the industrial application of the invention Since the main purpose of synthesizing the formulated nanoemulsion is to combat acne-causing bacteria, this invention can be used in the health industry related to acne improvement and treatment lotions.

Claims

Claims What is claimed: Claim 1) It is claimed that the formulation presented in this invention is based on oil-in-water nanoemulsion technology and consists of the following ingredients: tea tree oil, willow bark extract, niacinamide, glycerin, decyl glucoside, ethylhexyl glycerin, phenoxyethanol, citric acid, xanthan gum, and purified water. Claim 2) According to claim number 1, herbal nanoemulsion of tea tree oil enriched with willow bark extract and niacinamide has antibacterial properties against acne-causing bacteria (Cotibacterium acnes) and acne treatment. Claim 3) According to claim 1, due to the use of decyl glucoside as a plant-based emulsifying agent and the simplicity of the emulsion system, the production process does not require the expenditure of thermal energy.

Images