Eucerin-based herbal nanoemulsion formulation for topical treatment of cutaneous macular amyloidosis

Abstract

The present invention relates to a topical herbal cream formulation with eucerin as a base, designed for the treatment of cutaneous macular amyloidosis, and comprising herbal extracts of turmeric, chamomile, and gotu kola. These compounds are formulated using nanoemulsion technology in the size range of 50 to 200 nm to provide more effective skin absorption. Eucerin as a carrier fat and moisturizer in this formulation provides greater stability and reduces itching and inflammation. This formula is free of cortisone and hydroquinone and is capable of industrial production for therapeutic and cosmetic-hygienic use.

Description

Description of the invention Title of the invention (as stated in the declaration) Formulation of a plant-based nanoemulsion with eucerin for topical treatment of cutaneous macular amyloidosis Technical background of the relevant invention This invention is in the field of pharmaceutical and cosmetic-health industries, focusing on herbal products and skin care. Its main objective is to provide a therapeutic product for chronic skin diseases, especially cutaneous macular amyloidosis, which is a common disease with annoying symptoms such as severe itching, inflammation, skin discoloration and deposition of amyloid fibrils in the dermis layer. This product, using nanoemulsion technology and herbal ingredients, offers a safe, effective and mass-producible solution for improving this disease. This cream can be used in skin clinics, pharmacies and the skin care market and is also suitable for sensitive skin due to its natural ingredients. Technical problem and stating the objectives of the invention Cutaneous macular amyloidosis is a chronic skin disease caused by the deposition of amyloid fibrils in the dermis layer of the skin and presents with the following symptoms: Severe itching: reduces patients' quality of life, disrupts sleep, and can lead to scratching and secondary infection. Local inflammation: includes redness, swelling, and warmth of the skin in areas such as the back, arms, chest, or legs, which can cause discomfort and pain. Hyperpigmentation: a brown or gray discoloration of the skin, which is aesthetically problematic and reduces patients' self-confidence. Amyloid deposition: accumulation of amyloid fibrils that is difficult to treat and requires novel therapeutic approaches. Limitations of available treatments: Topical corticosteroids (such as betamethasone 0.1% or clobetasol 0.05%) temporarily reduce inflammation and itching, but long-term use (more than 4 weeks) can cause side effects such as skin thinning, striae, telangiectasia, or skin atrophy. Hydroquinone (2-4%) is used to reduce skin discoloration, but it carries risks such as skin irritation, photosensitivity, or exogenous ecchymosis (permanent discoloration) and is legally restricted in some countries. Simple moisturizers (such as Eucerin, Vaseline, or urea-containing creams) only maintain skin moisture and have limited effect on itching, inflammation, or amyloid deposition. Invasive procedures (such as laser therapy, dermabrasion, or cryotherapy) are expensive, painful, and have limited availability, with variable results. In addition, the lack of highly absorbed herbal formulations with specific efficacy for macular amyloidosis has created a huge gap in the treatment of this disease. The aim of this invention is to develop a nanotechnology-based cream to improve macular amyloidosis and reduce the side effects of existing treatments. A description of the state of the prior art and the history of developments related to the claimed invention. Current treatments for macular amyloidosis include: Topical corticosteroids: such as betamethasone or clobetasol, which are unsuitable for long-term use due to side effects such as skin thinning. Hydroquinone: Used to reduce hyperpigmentation, but carries the risk of skin irritation or permanent discoloration. Moisturizers: such as Eucerin or Vaseline, which have limited effectiveness and are not suitable for specific treatment. Invasive methods: such as laser and light therapy, which are expensive. Recent studies have shown that herbal extracts such as turmeric (containing curcumin with anti-inflammatory and antioxidant properties), chamomile (containing bisabolol and chamazulene with soothing effects), and gotu kola (containing asiaticoside and madecassoside with restorative properties) are beneficial for skin diseases. However, specific nano-formulations for macular amyloidosis have not been reported. This invention provides a safer, more effective and higher absorption solution by combining these extracts in a stable nano-emulsion system and stabilizing them in a eucerin base. Also, after searching the Iranian Patent Office and the Google Patents website at www.google.patents.com with the keyword "macular amyloidosis" in the Iranian Patent Office and "macular amyloidosis" in Google Patents, no title was found in the Patent Office. Providing a solution to an existing technical problem along with an accurate, sufficient, and integrated description of the invention This invention provides a Eucerin-based herbal nanoemulsion cream containing extracts of turmeric, chamomile, and gotu kola. These compounds were selected for the following properties: -Turmeric (curcumin): Reduces inflammation through inhibition of pro-inflammatory cytokines such as α-TNF and IL-6, antioxidant properties, and reduces the deposition of amyloid fibrils. -Chamomile (bisabolol and chamazulene): Relieves itching, reduces redness and inflammation of the skin by modulating immune responses. -Gotu Kola (asiaticoside and madecassoside): Stimulates collagen production, skin tissue regeneration, and repair of skin lesions. Nanoemulsion technology increases the penetration into the dermis layer by up to 3 times by producing particles of 10-50 nm (average 30 nm). Eucerin base (currently prescribed to keep patients' skin moisturized): Retains skin moisture and improves absorption by creating an occlusive layer. Ensures formulation stability (12-month shelf life). It is suitable for sensitive skin and prevents dryness caused by the disease. Composition and weight percentage Turmeric extract 20g, 2% by weight, containing at least 3% curcumin, selected for its curcumin content (a polyphenol with anti-inflammatory and antioxidant properties). Curcumin in higher concentrations (more than 3%) may cause yellowing of the skin or irritation in sensitive skin. Chamomile extract 15 g, 1.5% by weight, was chosen for its soothing, anti-inflammatory and antipruritic properties (especially due to bisabolol and chamazulene). Concentrations higher than 2% may cause unnecessary viscosity increase or production cost. Gotu Kola Extract 10g, 1% w / w, (containing 0.5-1% asiaticoside and madecassoside) Gotu Kola was selected for its regenerative and collagen-forming properties. Higher concentrations may not provide significant additional efficacy and increase production costs. The optimal amount helps improve skin structure and reduce amyloid deposition, and with nanoemulsion, increases penetration into the dermis layer. 100g coconut oil, 10% by weight, is chosen as a fatty and moisturizing carrier that helps the penetration of plant extracts and maintains skin moisture. This amount is sufficient to create a stable emulsion and moisturizing. Polysorbate 80 20 g, 2% by weight, is selected as a non-ionic emulsifier with HLB=15 to form a stable nanoemulsion. This amount is sufficient to form nanoparticles with a size of 10-50 nm and high stability. This emulsifier helps in the formation of nanoparticles and prevents the separation of oil and water phases. Eucrine 700g, 70% by weight, Eucerin is selected as a fatty and moisturizing base that complies with the USP Pharmacopoeia standard. This amount is ideal for creating the right texture, moisturizing and stability of the formulation. Eucerin creates an occlusive layer that retains moisture and facilitates the penetration of active ingredients into the skin. 135g distilled water, 13.5% by weight, distilled water was used as the aqueous phase to form the oil-in-water emulsion. Based on the oil-to-water phase ratio (1:3) in the skin nanoemulsions, the emulsion stability and viscosity are suitable for the cream. A percentage less than 10% may cause excessive viscosity increase, and a percentage higher than 15% can reduce the emulsion stability. Distilled water helps to dissolve water-soluble additives (such as hyaluronic acid) and form the nanoemulsion. Add-ons: Vitamin E: 2 grams (0.2% by weight, antioxidant to prevent oxidation). Hyaluronic acid: 1 gram (0.1% by weight, deep hydrating). Aloe vera extract: 2 grams (0.2% by weight, soothing and anti-inflammatory). Invented production method: The production process of this cream is designed to produce a stable, safe and effective product by observing pharmaceutical standards and using industrial equipment. This method includes the steps of preparing raw materials, extracting plant extracts, forming nanoemulsions, combining with Eucerin base, quality control and packaging. Each step is described in detail below: -Selection and preparation of raw materials Herbal ingredients: Turmeric root, chamomile flower and gotu kola leaf (spoon juice) are prepared in pharmaceutical quality according to pharmacopoeia standards. The herbs are subjected to microbial tests to check for contamination with bacteria such as E. coli or Pseudomonas and chemical tests (to confirm the percentage of active compounds such as curcumin, bisabolol and asiaticoside). Chemical ingredients: Coconut oil (pharmaceutical grade with 99% purity), Polysorbate 80 grade (USP), Eucerin grade (USP), distilled water (high purity, free of ions), Vitamin E (tocopherol, 98% purity), hyaluronic acid and aloe vera extract (pharmaceutical grade) are selected. Preparation process: Dried plants are washed, crushed and ground to fine particles (0.5-1 mm in size) (this is done with an industrial grinding machine such as a Hammer Mill at room temperature of 25°C to prevent degradation of the active compounds). The chemicals are stored in sterile containers and weighed before use. -Extraction of plant extracts Extraction method: Extracts of turmeric, chamomile and gotu kola are made by liquid-liquid extraction method with 70% ethanol solvent (pharmaceutical grade). 100 g of dry plant is mixed with 500 ml of 70% ethanol in a glass reactor equipped with a magnetic stirrer. The extraction process is carried out at 40±2°C for 24 hours with a stirring speed of 200 rpm. The extracted solution is filtered with a paper filter (Whatman No. 1) and concentrated with a rotary evaporator at 45°C and reduced pressure (100 mbar) to remove the solvent. These extracts are stored in dark containers at 4°C to prevent light degradation. The purity of the extracts was confirmed by high-performance liquid chromatography (HPLC) (C18 column, mobile phase methanol:water 70:30, UV-Vis detector at wavelengths of 425 nm for curcumin, 210 nm for bisabolol, and 220 nm for asiaticoside). -Preparation of oil phase Turmeric extract, chamomile extract, gotu kola extract, coconut oil and polysorbate 80 are mixed in a stainless steel reactor (pharmaceutical grade). The mixture is homogenized at 40±2°C for 30 minutes with a mechanical stirrer (speed 300 rpm) to form a uniform oil phase. The temperature below 45°C is chosen to prevent the degradation of active compounds (such as curcumin). A clear and stable oil phase with a viscosity suitable for nanoemulsion formation is obtained. -Preparation of aqueous phase Distilled water, hyaluronic acid and aloe vera extract are mixed in a separate container. The distilled water is heated to 40°C and the hyaluronic acid is slowly added until completely dissolved (stirring for 10 minutes at 200 rpm). Then the aloe vera extract is added and the mixture is homogenized for 5 minutes. A uniform aqueous phase with a pH of about 6 is prepared for mixing with the oil phase. -Formation of nanoemulsion The oil phase is added slowly (at a rate of 5 ml / min) to the aqueous phase and the mixture is processed with a high-pressure homogenizer or ultrasonic device (20 kHz, 10 min, power 500 W). The formation of nanoparticles with a size of 10-50 nm to increase skin permeability is the goal of this step. The particle size is measured with a Dynamic Light Scattering (DLS) device. The polydispersity index (PDI) should be less than 0.3 to confirm particle uniformity. The zeta potential is measured to check the stability of the emulsion. A stable nanoemulsion with fine particles and uniform distribution is obtained, ready for incorporation into the Eucerin base. -Compound with Eucerin base Nanoemulsion (165 grams), Eucerin (700 grams), and Vitamin E (2 grams) as antioxidants. Eucerin is melted at 50°C and placed in an industrial mixer (speed 500 rpm). The nanoemulsion is slowly added to Eucerin and homogenized for 20 minutes. Vitamin E is added at the last stage and the mixture is stirred for another 5 minutes. The temperature is gradually reduced to 25°C to prevent phase separation. -Final quality control The pH is measured with a pH meter and should be in the range of 5.5-6.5 to match the pH of the skin. It is measured with a viscometer (Brookfield, spindle 5, 10 rpm) to ensure that the texture of the cream is suitable for topical use. The cream is stored at 25°C and 60% humidity for 12 months and tests are performed for phase separation, color change or odor. The cream is tested for contamination with bacteria (E. coli, Pseudomonas aeruginosa and fungi (e.g. Candida albicans)) using standard USP methods. Skin permeability is tested using a Franz Diffusion Cell and artificial skin. The results show that nanoparticles penetrate the dermis up to 3 times more than non-nano formulations. -Packaging and storage The cream is packaged in 30 g sterile aluminum or plastic tubes with a sealed cap. Each tube is supplied with a label containing product information (ingredients, method of use, production date and expiration date). The cream is stored at a temperature of 15-25 ° C and away from direct sunlight. The shelf life of the product is 12 months. Table 1: Compositions and weight percentages Ingredient Amount (grams) Weight percent Role Turmeric extract 20 2% Anti-inflammatory, antioxidant, amyloid reduction Chamomile extract 15 1.5% Itch relief, anti-inflammatory Gotu kola extract 10 1% Tissue repair, collagen formation Coconut oil 100 10% Moisturizing, polysorbate carrier 80 20 2% Emulsifier Eucerin 700 70% Fatty base, moisturizing Distilled water 135 13.5% Aqueous phase Vitamin E 2 0.2% Antioxidant Hyaluronic acid 1 0.1% Hydrating Aloe vera extract 2 0.2% Soothing Explanation of shapes, maps and diagrams Figure (1) shows the materials required for the claimed invention. A clear and precise statement of the advantages of the claimed invention over prior inventions. 1. Safe herbal ingredients: Uses extracts of turmeric, chamomile, and gotu kola without side effects, unlike corticosteroids (skin thinning) or hydroquinone (irritation and sensitivity). 2. High absorption with nanotechnology: 10-50 nm particles increase permeability by up to 3 times, unlike traditional formulations with poor absorption. 3. Multifaceted efficacy: Reduction of itching, inflammation, skin discoloration, and amyloid deposition that existing treatments do not fully provide. 4. Suitable for sensitive skin: Free of irritants, suitable for long-term use without the risk of allergies. 5. Economical and industrial: Low production cost and mass production capability for domestic and export markets. 6. High stability: 12-month shelf life without degradation or phase separation, unlike some unstable herbal formulations. Description of at least one implementation method for implementing the invention 1. Skin preparation: Wash the affected area (such as the back, arms, or chest) with lukewarm water and mild soap and dry. 2. Using the cream: Apply 0.5 grams of cream (the size of a pea) for every 10 square centimeters of skin, twice a day (morning and night), gently massaging until absorbed. 3. Severe cases: For deep lesions, apply 1 gram of cream at night and cover with a thin bandage to leave on the skin overnight. 4. Precautions: Avoid contact with water or detergents immediately after use. Do not use the cream near the eyes or on open wounds. 5. Duration of use: For optimal results, use the cream continuously for at least 4 weeks. In cold seasons or for dry skin, continue regular use. 6. Sensitivity test: Before extensive use, test a small amount of cream on a small area of ​​skin (such as the inside of the wrist) and wait 24 hours to ensure no sensitivity. Explicit mention of the industrial application of the invention This invention is designed for mass production of therapeutic creams in the pharmaceutical and cosmetic-healthcare industries. Its main applications include: Treatment of macular amyloidosis: Reducing symptoms of itching, inflammation, skin discoloration, and amyloid deposition. Sensitive skin care: Suitable for dry, damaged skin or skin with diseases such as eczema and psoriasis. Beauty products: Improves the softness, smoothness, and appearance of skin for use in personal care products. Commercial markets: Supply to skin clinics, pharmacies and cosmetic markets with export potential due to global demand for herbal products. Complementary uses: Use in complementary treatments for other skin conditions such as superficial wounds or chronic inflammations. The product is supplied with a standard manufacturing process and packaged in sterile tubes with a label containing product information (composition, method of use, expiration date). Low production cost and high safety make this cream an attractive option for consumers and manufacturers. Brief description of the invention The present invention relates to a topical herbal cream formulation with eucerin as a base, designed for the treatment of cutaneous macular amyloidosis, and containing herbal extracts of turmeric, chamomile, and gotu kola. These compounds are formulated through nanoemulsion technology in dimensions of 10 to 50 nanometers to provide more effective skin absorption. Eucerin as a carrier of fat and moisturizer in this formula provides greater stability and reduces itching and inflammation. This formula is free of corticosteroid and hydroquinone and is capable of industrial production for therapeutic and cosmetic-hygienic applications.

Claims

Claims What is claimed:

1. Topical nanoemulsion cream formulation containing turmeric, chamomile, and gotu kola extracts with a therapeutic effect on macular amyloidosis.

2. The topical cream of claim 1, wherein the nanoemulsion particle size was confirmed to be between 10 and 50 nm by transmission electron microscopy (TEM) to effectively penetrate the dermis layer of the skin and reduce amyloid accumulation.

3. Method for producing a topical cream as claimed in claim 1, comprising the following steps: Preparation of the oil phase: mixing extracts of turmeric, chamomile, gotu kola, coconut oil (10%) and polysorbate 80 (2%) at a temperature of 40 ± 2 ° C for 30 minutes; 2. Preparation of the aqueous phase: dissolving hyaluronic acid and aloe vera extract in distilled water (13.5%) at a temperature of 40 ° C; 3. Formation of nanoemulsion: gradual addition of the oil phase to the aqueous phase and processing with: high-pressure homogenizer (200 bar, 3 cycles) or ultrasonic (20 kHz, power 500 W, 10 minutes); 4. Mixing with the base: adding the nanoemulsion to melted eucerin (temperature 50 ° C) and homogenizing for 20 minutes; 5. Controlled cooling to 25 ° C and adding vitamin E; 6. Quality control: pH 5.5–6.5, viscosity, particle size.

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