System and device for nanoliposome production
The dual-reservoir system with a cavitation homogenizer and advanced control systems addresses the challenges of precise parameter control and phase integration in nanoliposome production, enabling efficient and stable nanoliposome manufacturing across scales.
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- HAMISHEHKAR HAMED
- Filing Date
- 2025-06-28
- Publication Date
- 2026-07-02
Smart Images
Figure IB2025056596_02072026_PF_FP_ABST
Abstract
Description
[0001] TITLE OF THE INVENTION
[0002] SYSTEM AND DEVICE FOR NANOLIPOSOME PRODUCTION USING TWO SEPARATE RESERVOIRS FOR LIPID AND AQUEOUS COMPONENTS, EQUIPPED WITH A CAVITATIONAL HOMOGENIZER SYSTEM
[0003] TECHNICAL FIELD OF THE INVENTION
[0004] The present invention relates to the design and construction of a dual-reservoir system equipped with a cavitational homogenizer, and also relates to a continuous circulation bypass and advanced control systems under specific pressure (vacuum) and defined temperatures in both reservoirs and the homogenizer pump, which is used for nanoliposome production in pharmaceutical and cosmetic-hygienic industries, and also pertains to advanced mixing and homogenization methods that, through precise adjustment of temperature, pressure, and mixing speed, provide a stable product with nanometric particle sizes according to various formulations.
[0005] PRIOR ARTS
[0006] In recent decades, nanoliposome production technology has received significant attention due to the high capability of these structures in encapsulating pharmaceutical and hygienic compounds. Conventional methods such as Thin Film Hydration and Ethanol Injection have enabled the production of nanoscale liposomes; however, most of these methods require complex laboratory equipment, long processing times, and difficult control of parameters such as temperature and pH. Moreover, creating a vacuum to remove solvents and prevent oxidation sometimes requires costly devices and protocols.To overcome these challenges, newer technologies such as emulsification using high-pressure homogenizers and microfluidic systems have been proposed, aiming to accelerate the production process while enabling more precise control over particle size and distribution. Nevertheless, the implementation of these methods on an industrial scale has faced technical and cost-related limitations. Many production lines lack integration between the lipid and aqueous phases and effective control of process conditions (temperature, pressure, vacuum, etc.). The present invention seeks to facilitate the nanoliposome production process at both laboratory and semi-industrial scales by simultaneously utilizing two independent reservoirs, a cavitational homogenizer system, and the capability of heating and vacuum, thereby offering a high-quality and stable product.
[0007] The article titled "Liposomes in Cosmeceutics," published in 2012, explores the role of liposomes in cosmeceutical products and their potential as drug carriers to enhance the efficacy of these products. Liposomes, which are vesicles with a bilayer phospholipid membrane, are capable of penetrating the epidermal barrier of the skin due to their structural similarity to biological membranes. They can transport active pharmaceutical and cosmetic compounds to deeper layers of the skin. This ability increases moisturization, improves the performance of active ingredients, and reduces the systemic absorption of these compounds, ultimately enhancing the efficacy of topical treatments. The article reviews the applications of liposomes in the treatment of skin diseases and the improvement of cosmetic formulations. The benefits of using liposomes include increased permeability of active compounds, enhanced efficacy at the target site, reduced systemic side effects, high biocompatibility, and the ability for controlled drug release. The article also addresses challenges such as the low stability of liposomes, high production costs, and difficulties in scaling up for industrial applications. Finally,the authors emphasize that with the growing demand for innovative cosmeceutical products, research and development in liposomal formulations could play a crucial role in the future of the pharmaceutical and cosmetic industries.
[0008] A Canadian invention with publication No. CA2186745A1 which was filed on 27 / 03 / 1995, titled "Liposome with Increased Retention Volume," presents a method for producing multilamellar liposomes that can retain a substantial volume of aqueous solution, especially water-soluble and uncharged drugs, in their internal aqueous phase. In this method, neutral phospholipids and charged phospholipids (both having a nearly saturated fatty acid chain with a minimum chain length of Cl 4) are dissolved in a volatile solvent in an appropriate weight ratio (between 3:1 to 200:1). The solvent is then evaporated under vacuum or using other methods to obtain a thin lipid film. Next, an aqueous solution containing the desired drug (and if necessary, sucrose or other substances for adjusting osmolality) is added to the lipid film, which is then vigorously mixed or ultrasonicated at a temperature above the phase transition temperature of the phospholipids to form multilamellar liposomes. To control the particle size (50 to 3000 nanometers), filters with specific pore sizes can be used. The weight ratio of neutral to charged phospholipids and the control of parameters such as fatty acid chain length, saturation degree, total phospholipid concentration, and mixing conditions lead to an increased capacity for retaining the internal aqueous phase, up to 5 milliliters of water per gram of phospholipid or more. These liposomes, once produced, can be autoclaved and exhibit good stability in blood and during storage.
[0009] A Chinese invention with Patent No. CN101209243B which was granted on 08 / 10 / 2010, titled "Liposome Medicament and Preparation Thereof," pertains to the production of liposomal drugs, which includes processes for creating drugs capable of encapsulating multivalent ionic drugs such as mitoxantrone, vincristine,vinorelbine, or vinblastine. These drugs are commonly used for cancer treatment. The production steps for these liposomal drugs include preparing a bilayer phospholipid in which phospholipids with a phase transition temperature higher than body temperature are used. To ensure the effective incorporation of the drug into the liposome, multivalent ions such as citrate, sulfate, or phosphate are employed to help the drug precipitate within the liposome. These liposomes are typically produced in sizes ranging from 30 to 80 nanometers, and processes such as freezing and thawing are used to improve liposome formation and particle size measurement. These liposomal drugs are specifically applied in tumor treatment and reducing the toxicity of the drugs.
[0010] A Chinese invention with patent No. CN112107693 B which was granted on 26 / 05 / 2023, titled "Liposome Particles, Method for Preparing Said Liposome Particles and Use Thereof," pertains to the production of nanoliposomes that can be used for the delivery of genetic materials. These liposomes consist of a phospholipid bilayer containing two different types of lipids. Oligonucleotides containing CpG motifs, which activate TLR9 receptors, are attached to the surface of these liposomes. These liposomes are particularly sized between 25 to 50 nanometers. The production steps for these liposomes include adding phospholipids to a solvent to form a mixture of liposomes, followed by the use of sonication (ultrasonic waves) to break and stabilize them. Subsequently, modified oligonucleotides are added to these liposomes to facilitate the effective delivery of genetic or therapeutic materials into cells. These liposomes exhibit greater stability compared to regular samples due to the thick DNA layer and can efficiently enter cells for gene regulation purposes.
[0011] An European invention with patent No. EP0331504B1 which was granted on 10 / 06 / 1999, titled "Liposome Composition," pertains to a liposomal compositioncontaining a drug solution with an osmotic pressure higher than the body fluids of warm-blooded animals. This liposomal composition is made from a liposome membrane with a phase transition temperature between 40 to 45 degrees Celsius. These drugs are particularly suitable for cancer tumor treatment in hyperthermia therapies. To produce these liposomes, an aqueous solution containing the drug and an osmotic pressure controlling agent with an osmotic pressure 1.2 to 2.5 times that of body fluids is prepared. This solution is then combined with phospholipids whose phase transition temperature lies between 40 and 45 degrees Celsius, forming a W / O (water / oil) emulsion. This emulsion is then subjected to solvent evaporation under vacuum conditions to form large unilamellar vesicles (LU Vs). In the next stage, these liposomes are dialyzed to remove any untrapped drugs, and ultimately, the drug is effectively released during hyperthermic treatments.
[0012] A Japanese invention with patent No. JP4649841B2 which was granted on 16 / 03 / 2011, titled "Method for Producing Liposome-Containing Preparation, and Liposome-Containing Preparation," pertains to the process for producing a liposomal drug, which includes various stages for the formation and preparation of liposomes. Initially, a solution containing a water-soluble drug and a solution containing phospholipids, at least one of which has a phase transition temperature higher than body temperature, is prepared. These solutions are then mixed using carbon dioxide in a supercritical or subcritical state, along with ultrasonic irradiation, to form the liposomes. In this process, the temperature of ultrasonic irradiation is set to be higher than the phase transition temperature of the phospholipids. Finally, a water-soluble drug, such as an anticancer drug or a contrast agent, is encapsulated within the liposomes. This method, using supercritical carbon dioxide as the primary solvent without the need for organic solvents, helps produce highly efficient liposomes for encapsulatingpharmaceutical drugs and contrast agents. These liposomes can effectively serve as carriers for water-soluble drugs in medical treatments and diagnostics.
[0013] A Japanese invention with patent No. JP6187961B2 which was granted on 30 / 08 / 2017, titled "Liposome Pharmaceutical Preparation and Production Method Thereof," concerns the production of liposomal drugs using multivalent ionic drugs, which are particularly suitable for treating diseases such as cancer. In this invention, multivalent drugs with two or more separation groups having a separation constant (pKa) between 4.5 and 9.5 are used as the active ingredient in the liposomes. The production process involves the following steps: first, phospholipids (such as hydrogenated phosphatidylcholine or DPPC) and cholesterol are dissolved in organic solvents, and after freeze-drying, a dry powder is obtained. This powder is then hydrated with a solution containing counter-ions to the drug, such as ammonium sulfate, at a temperature of 60 to 65 degrees Celsius to form multilayer vesicles. The size of these vesicles is then reduced using microfluidizer devices or high-pressure devices. After liposome formation, either active or passive methods are used to load the drug into the liposomes. Here, the drug (such as mitoxantrone) is added to the liposomes in appropriate ratios, and the drug loading is performed at 60 to 65 degrees Celsius. Finally, the drug-loaded liposomes are tested for drug loading efficiency.
[0014] A Japanese invention with patent No. JP2006298844A which was granted on 21 / 04 / 2005, titled "Liposome-Containing Preparation Given by Including Pharmaceutical Compound in Liposome," pertains to a method for producing a liposomal drug that includes pharmaceutical compounds with high encapsulation efficiency within liposomes. In this method, the components of the liposomal membrane (which include phospholipids and other sterol and PEG lipids), along with the desired drug and excipient additives, are combined in a pressurized vessel.This mixture is then mixed with supercritical carbon dioxide at specific pressure and temperature (between 40 to 65 degrees Celsius), and the pressure is gradually reduced to obtain an aqueous suspension of liposomes containing the drug. The suspension is then maintained at a temperature higher than the phase transition temperature of the phospholipids (about 10 degrees Celsius higher) for a specified period (between 0.1 to 3 hours) to ensure proper lipid degradation and mixing. Finally, a low-pressure filtration operation is carried out to produce liposomes with a specified and uniform particle size. This method can produce liposomes with high encapsulation rates and suitable stability for various drugs, including anticancer drugs or contrast agents in medical imaging, without using harmful organic solvents.
[0015] A Japanese invention with publication No. JP2006508126A which was filed on 06 / 11 / 2003, titled "Protein-Stabilized Liposome Formulation of Pharmaceutical Formulation," pertains to a method for producing protein- stabilized liposomal formulations that are especially used for drug delivery. In this invention, an organic solution containing one or more phospholipids is first prepared. The desired drug is then added to this solution, and the mixture is injected into an aqueous solution containing emulsifying proteins to form an emulsion. The organic solvent is then removed from the emulsion to obtain a stable protein- stabilized liposomal formulation. In this method, in addition to phospholipids, cholesterol and polyethylene glycol (PEG)-modified phospholipids are used to enhance the stability and efficiency of the liposomes. These formulations, in nanometer sizes, are used as carriers for organic or hydrophobic drugs for treating various diseases, including cancer and vascular diseases.
[0016] A Korean invention with patent No. KR101495951B1 which was granted on 25 / 02 / 2015, titled "Liposome Composition," refers to a new liposomal compositionthat includes eribulin or its pharmaceutically acceptable salts. This invention provides methods for preparing a high-efficiency liposomal composition of eribulin with suitable stability. In this method, a liposomal solution is first prepared, which contains ammonium salts in the internal phase of the liposome. This solution is then mixed with eribulin or its pharmaceutically acceptable salts, allowing the active substance to be incorporated into the internal phase of the liposome. The pH of the internal phase of the liposome is then adjusted to effectively encapsulate eribulin within the liposome. This process is performed to optimize the encapsulation rate and the stability of the active ingredient within the liposomes. The final composition is available in either solid or liquid form and can be used for the treatment of cancer or other disease conditions.
[0017] A Korean invention with patent No. KR101810160B1 which was granted on 25 / 01 / 2018, titled "Generating Method for Ethosome with Bioactive Compounds, Ethosome and Cosmetic Composition Including Ethosome," pertains to the production of ethosomes containing bioactive compounds. In this production method, an aqueous solution of a bioactive substance is first prepared. Then, a lipid solvent solution containing lipids in alcohol is prepared. These two solutions (aqueous solution and lipid solvent solution) are combined to produce a hydrated crystalline liquid phase. Subsequently, purified water is added to the crystalline liquid phase, and the mixture is gently stirred to produce the ethosomal solution. This process is designed to produce nanoparticles and increase skin absorption rate. Additionally, in some stages, high-pressure homogenization is used to reduce particle size and improve stability. This ethosome production technique is capable of being used in the formulation of high-efficiency cosmetic and pharmaceutical products with reduced skin damage.A Russian invention with patent No. RU2642640C2 which was granted on 25 / 01 / 2018, titled "Disposable System for Sterile Obtaining of Lipids and Nucleic Acids Particles," refers to a system for producing sterile lipid nanoparticles and nucleic acid molecules (such as RNA) designed to provide uniform and reproducible particles under sterile, single-use conditions. In this system, an organic solution containing lipids is first prepared in an organic solvent that is mixable with water (such as ethanol). This solution is then introduced into a mixing unit along with an aqueous solution containing nucleic acid molecules (such as siRNA). At this stage, the organic solution is added to the nucleic acid solution in the mixing chamber to create a concentration gradient. After this, the mixture is transferred to a dilution unit and then to a membrane filter to remove the organic solvent and concentrate the liposomal nanoparticles. These nanoparticles are then prepared for therapeutic uses, and if necessary, a freeze-thaw operation is performed to enhance the stability of the final product. This system is made of sterile and disposable parts, facilitating the rapid and safe production of lipid nanoparticles containing nucleic acid drugs.
[0018] A Russian invention with patent No. RU2728976C2 which was granted on 03 / 08 / 2020, titled "Liposomal Composition and Preparation Thereof," pertains to the process of producing liposomes for drug delivery by forming lipid nanocapsules. In this invention, a therapeutic drug (such as alendronate) is combined with lipids such as distearoylphosphatidylcholine (DSPC), distearoylphosphatidylglycerol (DSPG), and cholesterol in a molar ratio of 3:1:2. This mixture undergoes a process involving several stages to produce nanocapsules called liposomes. Initially, the drug solution and lipid solution are combined to create multilamellar vesicles (MLVs). These vesicles are then passed through a filter with a specific pore size (such as 100 nanometers) under low pressure toreduce particle size and achieve the desired size. After this stage, an ultrafiltration process is used to remove any free drug and lipid and separate the liposome particles. This process also improves particle size uniformity and formulation stability. After ultrafiltration, the solution is adjusted to standard conditions and sterilized through filtration to prevent contamination. Finally, the liposome production process, including particle size control, drug-to-lipid ratio, and other physical and chemical characteristics, is carried out to ensure drug efficacy. This method is particularly useful on a commercial scale as it reduces production costs and shortens production time.
[0019] A US invention with patent No. US5169635 A which was granted on 08 / 12 / 1992, titled "Photoresponsive Liposome," pertains to the production of light-responsive liposomes for various applications, such as diagnosis and treatment in medicine. These liposomes contain a light-sensitive compound capable of controlling the release rate of substances inside the liposomes using light irradiation. To produce these liposomes, a light-sensitive compound that contains both hydrophilic and hydrophobic groups is first selected. This compound is then used as a primary component in the formation of the liposomal membrane. The subsequent liposome production process includes dissolving phospholipid compounds, cholesterol, and polymer-modified compounds such as (DSPE-PEG) in suitable solvents like chloroform. After removing the solvent from the solution, a thin film is obtained, and the process continues with methods such as vortexing or sonication in the presence of a buffer solution containing active ingredients. These methods result in the production of liposomes with suitable particle sizes (typically 30 to 80 nanometers). Then, the content inside the liposomes can include pharmaceutical or other active substances such as anticancer agents, antivirals, or antibiotics, whichare gradually released from the liposomes upon light exposure. These liposomes have widespread applications in targeted therapy and controlled drug release.
[0020] A US invention with patent No. US9737528B2 which was granted on 22 / 08 / 2017, titled "Liposomes Useful for Drug Delivery to the Brain," pertains to the formulation and methods of manufacturing liposomes that are useful for drug delivery to the brain. In this invention, the liposome production process involves the use of substituted ammonium compounds or poly-ionic compounds for loading and retaining substances inside the liposomes. These liposomes can contain therapeutic or imaging compounds. The production process typically involves combining a substituted ammonium compound with poly-ions and then using these compounds to load substances into the liposomes. Additionally, the liposome structure typically includes phospholipids, cholesterol, and polymer-modified lipids like PEG. These liposomes can effectively target drugs to the brain, and since the substances inside the liposomes are loaded via specific processes such as "transmembrane gradient," these compounds can be effectively used in the treatment of various diseases and conditions.
[0021] A US invention with patent No. US9839616B2 which was granted on 12 / 12 / 2017, titled "Lipid Nanoparticles Comprising Cationic Lipid for Drug Delivery System," pertains to lipid nanoparticles that include liposomes for carrying and delivering genetic drugs. These nanoparticles are made by combining cationic lipids, known as compound (I), with nucleic acids. Compound (I) includes a complex molecule specially designed to interact with nucleic acids and form stable complexes. To produce these lipid nanoparticles, compound (I) and nucleic acids are dissolved in solvents such as ethanol or chloroform and then lipid nanoparticles are formed using methods such as reverse emulsification. These nanoparticles may consist of a single or bilayer lipid membrane encapsulating the nucleic acids. Additionally, insome methods, neutral lipids and polymers are also used to enhance the stability of the nanoparticles. One of the advantages of these nanoparticles is their ability to be used in the treatment of inflammatory and cancerous diseases by delivering genetic drugs like siRNA to cells.
[0022] A US invention with patent No. US9968583B2 which was granted on 15 / 05 / 2018, titled "Method of Manufacture of Liposome Composition," presents a new method for producing a liposomal composition, which includes several main steps. In the first stage, a liposome dispersing liquid is prepared, in which liposomes along with cyclodextrin are present in the internal phase of the liposome. In the next stage, a solution containing the active compound (or its pharmaceutically acceptable salt) is prepared. This solution is then combined with the liposome dispersing liquid. In this stage, the active compound enters the internal phase of the liposome, and this process increases the concentration of cyclodextrin in the internal phase relative to the external phase of the liposome. The combined solution is then heated to a temperature equal to or higher than the phase transition temperature of the liposomal membrane. This process leads to the production of a liposomal composition in which the active compound forms a complex with cyclodextrin in the internal phase of the liposome. This method, by using cyclodextrin, enhances the encapsulation ratio of the active compound in the liposome and improves the stability of the active compound in the bloodstream. This invention is particularly useful for improving pharmaceutical formulations and enhancing the delivery of pharmaceutical compounds to target tissues.
[0023] A US invention with Patent No. US9993427B2 which was granted on 12 / 06 / 2018, titled "Liposome Formulation and Manufacture," pertains to the formulation and production process of liposomes specifically designed for carrying therapeutic materials. In this invention, the production process includes specific stages tocreate liposomes with uniform size and physical properties, improving the efficiency and stability of the composition. Initially, a solution containing the therapeutic agent is combined with a lipid solution containing specific lipids such as distearoylphosphatidylcholine (DSPC), distearoylphosphatidylglycerol (DSPG), and cholesterol in a 3:1:2 molar ratio. This mixture is then passed through a filter with 100-nanometer pore size to produce uniform liposomes. After this step, ultrafiltration is carried out to remove excess and unencapsulated materials (such as free drug and other solvents). Finally, to achieve the final drug concentration, a dilution process with phosphate-buffered saline solution is carried out. This production method, using low pressure and a single-step extraction, reduces operational costs and production time while increasing the production yield. The produced liposomes, due to characteristics such as enhanced membrane rigidity, an appropriate drug-to-lipid ratio, and size uniformity, are optimized for therapeutic use.
[0024] A US invention with patent No. US 10028913B2 which was granted on 24 / 07 / 2018, titled "Liposomal Pharmaceutical Preparation and Method for Manufacturing the Same," refers to the production of a specific liposomal drug formulation that encapsulates multivalent ionic drugs. This liposomal formulation has a size range of approximately 30 to 80 nanometers, in which the phospholipid layer consists of phospholipids with a phase transition temperature higher than body temperature, ensuring that the liposome’s phase transition temperature is higher than body temperature. In this production method, phospholipids such as hydrogenated soy phosphatidylcholine (HSPC) and cholesterol are first dissolved in an organic solvent and then lyophilized to obtain a dry powder. This powder is then rehydrated with a solution containing various ions, transforming it into multilayer liposomes. The size of these liposomes is then reduced using amicrofluidizer or pressure device to achieve the desired size. The next stage involves loading the desired drug, typically a multivalent ionic drug such as mitoxantrone, into the liposomes. This process uses either active or passive drug loading methods. Finally, various methods, such as gel filtration chromatography, are used to determine the drug loading efficiency. These liposomes, after preparation, are used for the treatment of diseases, especially various types of cancers.
[0025] A US invention with patent No. US10363217B2 which was granted on 30 / 07 / 2019, titled "Nano-liposome carrier composition containing hybrid of Cas9 protein and guide RNA," pertains to nano-liposome carrier compositions containing a hybrid of Cas9 protein and its guide RNA. These compositions are effectively used as nano-liposome carriers for treating diseases such as type 2 diabetes. The production stages of these nano-liposomes include several steps: combining guide RNA and Cas9 protein: first, a specific guide RNA is produced that binds to a target DNA sequence such as the DPP4 gene. This guide RNA is combined with the Cas9 protein to form a CRISPR hybrid; preparation of a lipid film: in the next step, lecithin, cholesterol, and a metallic lipid (specifically used for binding proteins to nano-liposomes) are combined in a chloroform solution to form a lipid film; combining the CRISPR hybrid with the lipid film: the Cas9 / guide RNA hybrid is combined with the lipid film and then subjected to ultrasonic waves. This step helps form nano-liposomes that encapsulate the protein and guide RNA; freezing and thawing: after the ultrasonic step, the mixture undergoes multiple freeze-thaw cycles (between 3 to 6 times) under specific conditions to uniformly adjust the nano-liposome size; centrifugation: finally, the mixture is centrifuged to collect the nano-liposomes containing the CRISPR hybridas a precipitate. These nano-liposomes can effectively enter cells and are used for treating diseases such as type 2 diabetes through gene editing.
[0026] A US invention with patent No. US11633358B2 which was granted on 25 / 04 / 2023, titled "Surface treatment by water-soluble polymers and lipids / liposomes," provides a detailed method for preparing liposomal compositions for drug delivery. In this process, lipid compositions including phosphatidylcholine, phosphatidylglycerol, and cholesterol are first mixed in specific ratios. The active drug is then added to these compositions to become encapsulated inside the liposomes. After that, these lipid compositions are transferred to an aqueous solution containing specific ions to create a pH gradient. This process leads to the formation of a liposomal bilayer membrane in which the drugs are entrapped. To improve size uniformity of the liposomes, the compositions undergo processes such as ultrafiltration and dialysis to increase liposome stability and size homogeneity. The final size of the liposomes is typically in the range of 80 to 100 nanometers, which is suitable for pharmaceutical applications. The compositions are then subjected to sterile filtration and standardization to become ready for commercial production.
[0027] A US invention with publication No. US20060008909A1 which was filed on 16 / 05 / 2005, titled "Liposomal formulations comprising dihydrosphingomyelin and methods of use thereof," pertains to the method of production and preparation of liposomes comprising dihydrosphingomyelin (DHSM). First, DHSM is obtained through hydrogenation of sphingomyelin (SM), in which the trans double bond in the sphingosine base chain is removed during the process. Then, the liposomes are prepared using standard methods such as dissolving the raw materials in ethanol and adding an aqueous solution to form a lipid film. After that, specific devices such as microfluidizers are used to reduce liposome size and form homogeneousstructures. Finally, the liposomes are loaded with drugs using various techniques such as pH gradient loading or ion-based methods. DHSM is used as one of the main components of the liposomal membrane in this process, and studies have shown that liposomes composed mainly of DHSM possess distinct structural properties that enhance long-term drug delivery stability and efficiency.
[0028] A US invention with publication No. US20110163468A1 which was filed on 27 / 08 / 2010, titled "Device for Preparation of Liposomes and Method Thereof," introduces a device for producing liposomes based on the double-emulsion method. This device includes a reaction chamber, an injection unit, and filters for processing various solutions. Initially, an aqueous solution and an organic solution are injected into the reaction chamber, creating an interface between the filter and the collector. Then, the aqueous solution containing bioactive substances (such as drugs or fluorescent dyes) passes through the filter, resulting in the formation of a water-in-oil emulsion. This emulsion is then converted into a water-in-oil-in-water emulsion. Finally, the organic phase is removed to obtain the liposomes. In this process, to enhance efficiency, a rotary evaporator is used to eliminate the organic solvent. This method has numerous advantages over traditional methods, including mass-production capability, controllability, and high packaging efficiency without the need for sonicators or complex microfluidic systems.
[0029] A US invention with publication No. US20110223675A1 which was filed on 20 / 11 / 2009, titled "Drug Release Means from Liposomes and Method for Evaluating Releasability," explains a method for drug release and evaluation from liposomes. Initially, to prepare the liposomes, the drug is loaded into the aqueous phase inside the liposomes using a remote loading method. This process involves using a solution with a suitable pH to create an ion concentration difference between the internal and external phases of the liposomes. This ion gradient causesthe drug to be efficiently transferred into the liposomes. After the liposomes are formed, a shift reagent is added to them, which alters the chemical equilibrium inside the internal aqueous phase of the liposomes. This change in chemical equilibrium triggers the release of the drug from the internal phase to the external phase of the liposomes. This process can be halted using heat or by adding a quenching solution. The quenching solution typically contains alkaline or acidic substances that adjust the pH of the environment and stop the drug release. In this way, drug release is precisely measured and can be used for evaluating the efficacy and quality control of liposomes during production. This method is suitable for evaluating drug release from liposomes without the need for laboratory animals or other biological materials and allows for accurate and reproducible measurement. A US invention with publication No. US20240122822A1 which was filed on 21 / 08 / 2023, titled "Liposomes, Emulsions, and Methods for Cryotherapy," describes methods for the production and use of liposomes for medical treatments, particularly in the field of cryotherapy and skin-related applications. In this method, a substance is applied to the surface of human skin that includes freezing point-depressing agents and various components such as liposomes, oil-in-water emulsions, water-in-oil emulsions, and nanoemulsions. These compositions are designed to enhance the absorption of the active ingredient and improve its delivery to the skin. Then, using an applicator, the applied substance and the skin surface are cooled to sub-zero degrees Celsius. The objective of this therapeutic process is to initiate a freezing event that causes the targeted tissue to freeze without damaging healthy tissues. In these systems, liposomes function as carriers for active substances such as antifreeze agents, which are released into the skin upon liposome breakdown. In some cases, this process is advanced using ultrasonic energy, thermal cycling, or cleansing agents to disrupt the liposomal membraneand release the active substances. These methods are specifically used for treating skin conditions such as acne and other inflammatory disorders. The therapeutic systems of this invention are capable of precisely controlling the timing and intensity of freezing to provide effective treatment without harming non-target tissues.
[0030] A WIPO invention with publication No. WO2015166985A1 which was filed on 30 / 04 / 2015, titled "Liposome Composition and Method for Producing Same," pertains to a liposome composition and a method for its production. In this invention, a liposome composition is introduced that contains an internal aqueous phase and an external aqueous solution in which the liposomes are dispersed. In this composition, the drug is dissolved in the internal aqueous phase, and the osmotic pressure of the internal phase is two to eight times higher than that of the external phase. This feature allows the drug release rate from the liposomes to be regulated within a range of approximately 10 to 70 percent over 24 hours at 37°C in blood plasma. The method for producing this composition includes several steps. In the first step, an oil phase is prepared by dissolving various lipids such as hydrogenated phosphatidylcholine, cholesterol, and polyethylene glycol conjugated with phosphatidylethanolamine in an organic solvent. This oil phase is then mixed with the aqueous phase to form an emulsion in which liposomes are formed. At this stage, the drug is loaded into the liposomes, and afterward, the osmotic pressure of the internal phase is precisely adjusted using various methods such as dialysis to achieve controlled drug release. Finally, to achieve long-term stability and precise control over the drug release rate, the liposomes are subjected to additional treatments such as filtration, solvent evaporation, and similar processes to obtain the final composition. This liposomal composition, in terms ofdrug release, controllability, and stability, is suitable for use in therapeutic drugs, including anticancer medications.
[0031] An article titled "Manufacturing of Liposomes by Using a Scale Independent Microfluidic Device: An Investigation into Design of Experiments" by Ahmad Mirkani, Mohammad Reza Nabid, and Sarvenaz Pakian investigates the process of producing liposomes using a scale-independent microfluidic device. This device is designed to improve liposome production, as conventional scalable production methods face limitations in industrial-scale manufacturing. The study focuses on experimental design of the process and related simulations using COMSOL software to model various parameters of the microfluidic mixer. The article also examines the effects of parameters such as concentration distribution, fluid velocity, streamlines, and pressure inside the mixer to identify which factors influence the quality and efficiency of liposome production. This study was conducted to assess the compatibility of the models with various mesh types in COMSOL software to ensure simulation accuracy and to compare the simulation results with experimental data.
[0032] An article titled "Microfluidic Methods for Production of Liposomes", published in 2009, discusses that liposomes are composed of lipid bilayer membranes enclosing an aqueous volume. One of the main challenges in the development of liposomes for drug delivery is the control of their size and size distribution. In traditional methods, lipids spontaneously assemble into heterogeneous bilayer structures in bulk phases. To obtain small liposomes with narrower size distributions, additional processing steps such as extrusion or sonication are required. Microfluidics is an emerging technology for liposome synthesis, as it allows precise control over the lipid hydration process. Here, several microfluidic methods are described that have been repeatedly reported for the production of micro / nano liposomes with smallersizes and narrower size distributions, with a focus on using continuous low-flow microfluidics. The article discusses the advantages of forming liposomes using microfluidic techniques compared to traditional bulk mixing methods.
[0033] An article titled "Industrial-scale Methods for the Manufacture of Liposomes and Nanoliposomes: Pharmaceutical, Cosmetic, and Nutraceutical Aspects", published on 23 / 10 / 2022, states that liposomes are microscale lipid bilayer vesicles widely used to encapsulate drugs and deliver them into the body with targeted delivery and controlled release. The nanoscale version of liposomes is known as nanoliposomes. These drug delivery systems, which are biocompatible and biodegradable, offer multiple advantages, such as the ability to encapsulate various drug molecules under physiological conditions. Compared to other delivery systems such as micelles, polymeric and metallic nanocarriers, or niosomes, liposomes are the most recognized and accessible carriers used not only in pharmaceuticals but also in cosmetic and nutraceutical products. However, the scaling-up of their production and ensuring sufficient stability are significant challenges for liposomes. This review discusses various industrial- scale methods for preparing liposomes, including organic solvent methods, freeze-drying of double emulsions, heating methods, Mozafari method, membrane contact method, liposome formation through curvature control, biomimetic liposome self-assembly, sonication method, extrusion method, spray drying, and microfluidic systems. Some of the factors contributing to physicochemical or biological instability and ways to overcome these challenges are also reviewed. Additionally, quality control procedures and regulatory considerations from international agencies for the development of liposomal and nanoliposomal pharmaceutical products are addressed.An article titled "Optimal Design of Micromixer for Preparation of Nanoliposomes", published in February 2024, explains that micromixers are essential components for controlling reactions in microfluidic devices and significantly enhance their efficiency. This article introduces an unbalanced separation-and-recombination micromixer with a swirling chamber and optimizes its geometric structure. The study investigates how the aspect ratio of the main subchannel and the secondary subchannel, as well as the position of the swirling chamber, affect the mixing index and pressure drop at the inlet and outlet of the micromixer. The enhanced mixing results from the unbalanced effect created by the separation and recombination mechanism of the micromixer, which combines with the synergistic effect of the self-rotating liquid flow. Simulation results show that the optimized micromixer achieves a mixing index close to 100% when the Reynolds number exceeds 30, with a pressure drop of only 30 kPa at a Reynolds number of 50. A microfluidic-based micromixer was fabricated using soft lithography and molding techniques. Liposomes were synthesized in a single step using soybean phospholipids, cholesterol, ethanol, and deionized water as raw materials. The micromixer demonstrated exceptional mixing performance, enabling faster liposome synthesis compared to conventional methods. Moreover, the resulting liposomes exhibited smaller particle sizes and narrower size distributions. By adjusting the flow rates of the aqueous and organic phases entering the micromixer, liposomes with a particle size of 39 nm and a focused size distribution (PDI = 0.104) were successfully produced. These findings highlight the microfluidic approach as a convenient, rapid, and efficient method for liposome preparation. Furthermore, the unbalanced separation-and-recombination micromixer with a swirling chamber showed a simple structure, high mixing efficiency, and low pressure drop. This versatile mixer is suitable for various applications in microreactors.An Australian invention with patent No. AU2014200717B2 which was granted on 25 / 02 / 2016, titled "Liposome Composition", relates to the production of a new liposomal composition containing the drug eribulin or its pharmaceutically acceptable salt. This composition is produced in a single step, in which liposomes are formed using specific methods such as the lipid film formation method or other techniques. To produce these liposomes, the internal phase of the liposome includes at least one ammonium salt and at least one acid or base such as sodium hydroxide, ammonia, hydrochloric acid, or acetic acid. A solution containing eribulin or its pharmaceutical salt is then prepared and combined with the liposomal solution to form the final composition. During the preparation process, particularly in the step involving the adjustment of the pH of the external phase of the liposome, precise control is applied to ensure the drug is effectively entrapped in the internal phase of the liposome. This liposomal composition demonstrates high drug encapsulation efficiency and pharmaceutical stability, which allows effective delivery to target tissues in the body. Overall, this invention contributes to the development of a new liposomal formulation with higher efficiency and greater stability compared to conventional methods, and is intended for use in anticancer drugs.
[0034] DESCRIPTION OF THE INVENTION
[0035] The present invention provides a dual-reservoir system for the production of gellike nanoliposomes in the pharmaceutical and cosmetic-hygienic industries, which enables controlled mixing and advanced homogenization by integrating the lipid phase in a small reservoir and the aqueous phase in a larger reservoir. This system is equipped with a cavitation homogenizer, a bypass system for continuous fluidcirculation, a heating-cooling jacket for the large reservoir, a heating jacket for the small reservoir, a cooling jacket for the homogenizer pump and its outlet pipe, a vacuum pump to create sealed conditions, and a glass lid for direct observation of the process. The dual-mode discharge valve design in the small reservoir, along with flow control of materials to the large reservoir, allows for ease of combination and rapid analysis of the process, ultimately resulting in a gel-like product with nanometric particle size and high stability.
[0036] The small reservoir (Fig. 8, No. 4) is the starting point of the nanoliposome production process in this invention and is responsible for the initial preparation of the lipid phase. Typically, compounds such as phospholipids, cholesterol, or a mixture of lipids, loaded with peptides or plant extracts or vitamins or natural products or drugs, are combined in this reservoir to form a uniform base for liposome formation. The input method of raw materials into this reservoir can be manual or automatic depending on the user's equipment, but what is crucial is the homogenization of all formulation components prior to transfer to the larger reservoir.
[0037] To ensure the homogeneity of the lipid phase, a low-speed mixer (Fig. 8, No. 3) is used inside the small reservoir. This mixer provides sufficient speed for effective mixing of the components, while its low rotational speed prevents the formation of foam or excess air bubbles. This feature is particularly important in the preparation of nanoliposomes, as the presence of excess air can lead to oxidation of sensitive substances and disruption in the nanometric particle size. If needed, the stirring speed can be adjusted to increase or decrease the intensity of mixing depending on the viscosity of the components.Structurally, the bottom of the small reservoir is designed as a truncated cone (Fig.
[0038] 7, No. 5), at the end of which a dual-mode valve is installed. This design ensures complete discharge of materials, leaving no residue in the corners of the reservoir. Additionally, the walls and bottom of the reservoir are made of 316 stainless steel to resist corrosion, heat, and possible chemical reactions. This grade of stainless steel also allows for easy cleaning and sterilization, preventing the growth of microorganisms during sensitive pharmaceutical and cosmetic processes.
[0039] Once the lipid materials in the small reservoir are fully homogenized and prepared, the valve (Fig. 7, No. 4) installed at the bottom of the reservoir is opened, allowing the components to be transferred through a stainless steel pipe to the large reservoir. This valve can be set in two modes: direct discharge to the outside (used when cleaning or removing waste is necessary) or staged transfer of materials to the main reservoir (to initiate homogenization with the aqueous phase). This control feature enables precise addition of the lipid phase to the aqueous phase, ensuring that the nanoliposome production process begins under stable and predictable conditions.
[0040] The small reservoir may be equipped with sensors and auxiliary connections to allow continuous monitoring of parameters such as temperature or pH, and to enable the evacuation of air from the reservoir or its replacement with an inert gas when necessary. This capability is particularly important in sensitive formulations, as it prevents premature oxidation of lipid compounds. Furthermore, the internal design of the reservoir facilitates Clean-in-Place (CIP) and Sterilize-in-Place (SIP) operations, allowing all product-contact surfaces to be washed and disinfected without the need to disassemble components. All of these features significantly contribute to the production of a high-quality and reliable product that complies with pharmaceutical and cosmetic industry standards.After the lipid phase is prepared in the small reservoir, the materials are transferred through the dual-mode valve at the bottom of the reservoir into the large reservoir either in a stepwise or continuous manner. The choice of discharge method (stepwise or continuous) depends on the desired speed of nanoliposome formation. In stepwise mode, the operator briefly opens the valve to allow a portion of the lipid components to enter the large reservoir, then closes the valve and waits for partial mixing with water, repeating this cycle if necessary.
[0041] As soon as the lipid phase enters the large reservoir, the homogenizer system (Fig.
[0042] 7, No. 1) installed beneath the reservoir is activated. Using cavitation, shear stress, impact, and flow turbulence mechanisms, it breaks down the lipid particles to the nanometric scale. In this method, extremely fine bubbles are generated in the aqueous flow and rapidly collapse, producing high mechanical energy that accelerates the fragmentation of the lipid phase and its dispersion into the water. The performance of this specialized homogenizer depends on the formulation of the materials, the blade design, the blade spacing, the motor rotation speed, and the internal pressure within its chamber. These parameters can be adjusted depending on the sensitivity or type of materials to achieve the desired particle size and uniformity. Unlike traditional methods that may require extended processing time or multiple stages, the use of this customized homogenizer allows the homogenization process to occur with greater speed and efficiency.
[0043] Alongside the homogenizer, an axial (or multi -blade) mixer (Fig. 4, No. 1) is installed within the large reservoir (Fig. 1, No. 5) to facilitate fluid movement throughout the entire volume of the tank and prevent sedimentation or phase separation. The combined action of the mixer and the homogenizer enables rapid mixing of the materials and the formation of initial liposomal structural stability.At this stage, the mixing process can be monitored by tracking the tank temperature and observing the contents visually through the glass lid.
[0044] To improve homogenization efficiency, a bypass system (Fig. 2, No. 2) in this invention is designed in the form of a closed-loop circuit that passes alongside the homogenizer and re-enters the upper part of the large reservoir. When the fluid inside the tank circulates through the high-pressure homogenizer, the bypass allows the solution to pass through the homogenizing unit multiple times, significantly enhancing the degree of homogenization. With such a system, lipid particles are repeatedly exposed to cavitation forces, reducing their size down to the nanometric scale.
[0045] Flow control in the bypass system is managed by one or more regulating valves that determine the degree of openness or closure of the return path. When the product reaches a desirable level of homogenization, the flow through the bypass can be reduced or halted to prevent energy waste. Additionally, the presence of this internal circulation loop contributes to maintaining uniform temperature inside the tank, as the fluid passes by the heating element, cooling stream, or temperature sensor and continues circulating throughout the reservoir. This mechanism not only improves product quality but also enhances process efficiency.
[0046] In addition to the homogenizer and bypass system described earlier, the large reservoir’s mixer plays a vital role in completing the mixing and homogenization process. This mixer, designed axially with multiple blades, extends from the top of the reservoir down to near its bottom, generating a continuous vertical flow within the tank. This vertical flow promotes better distribution of lipid particles throughout the entire tank volume, preventing sedimentation or layering. Furthermore, the mixer is made of mirror-finished 316 stainless steel, which offersresistance to corrosion and chemical reactions, while also allowing for easy and thorough cleaning and sterilization. The mixer’s speed and direction of rotation can be adjusted according to the viscosity and operational requirements to ensure that the final product reaches the desired quality.
[0047] To achieve optimal conditions for nanoliposome production, the temperature within the large reservoir must be precisely controlled. For this purpose, the large tank is equipped with a heating-cooling jacket that enables controlled heating and cooling of the tank contents within a range of 4 to 70 degrees Celsius. This controlled temperature reduces the viscosity of the lipid phase, facilitates the mixing process, and establishes a stable environment for the formation of nanoliposomal structures. The heating system is evenly distributed along the tank walls to prevent the formation of hot spots or localized temperature differences. To this end, a water heating tank (Fig. 10, No. 1) is installed adjacent to the large tank, equipped with a heating element (Fig. 10, No. 2), as well as two water inlet and outlet pipes (Fig. 10, Nos. 3 and 4), which supply the hot water required for heating the large tank.
[0048] To ensure precise temperature control of the tank, a rod-type thermometer (temperature sensor) (Fig. 2, No. 1) is installed inside the large reservoir, which continuously measures the exact temperature of the liquid and sends the data to the central control system. This thermometer allows the operator to regulate and stabilize the temperature throughout the process, and if necessary, it automatically activates or deactivates the heating system. As a result, unwanted temperature fluctuations are eliminated, yielding a product with stable and uniform particle size.Additionally, to better control the internal environmental conditions of the tank and to reduce the harmful effects of oxygen and air bubbles, a vacuum system using a vacuum pump (Fig. 3, No. 1) has been designed for both the large and small reservoirs. This system can evacuate air and other interfering gases (including ethanol or unwanted vapors) from the tank before or during the process. By creating a partial vacuum, it prevents the oxidation of sensitive compounds. All seams and access ports of the tank are fully sealed to optimize the performance of the vacuum system and enhance the quality of the final product. Additionally, to eliminate the water vapor generated inside the large tank, a condenser (Fig. 9, No.
[0049] 2) has been designed to capture the vapor and store it in a tank (Fig. 9, No. 1) in liquid form.
[0050] One of the important features of the device is the specially designed main lid of the large reservoir, located at the top of the tank. This arrangement significantly reduces the overall height of the system. This lid is made of durable glass, allowing the operator to directly observe and monitor the production process. In addition, the surrounding area of the lid is precisely sealed so that during vacuum evacuation of the tank or during the injection of specific gases such as nitrogen, the internal pressure of the tank remains well maintained.
[0051] To enhance operator visibility and facilitate process monitoring, a wiper system (Fig. 1, No. 2) is installed on the glass section of the main lid (Fig. 1, No. 4). This system cleans the glass surface in case of condensation or accumulation of liquid droplets, ensuring clear and continuous visibility. Additionally, the presence of sodium lamps (Fig. 1, No. 3) in this section allows the operator to better assess the color, clarity, and appearance of the mixture, enabling them to detect any changes in the product's structure in a timely manner.The large tank is a triple-walled (jacketted) vessel and is connected to a hot and cold water system for temperature regulation in the range of 4 to 70 degrees Celsius. The vacuum pump is located at the top of the tank. The bottom of the large tank is designed in a conical shape (Fig. 7, No. 2). This tank is equipped with an easily replaceable mixer (Fig. 2, No. 2) and scrubber (Fig. 6, No. 3). Additionally, the large tank features a digital temperature sensor inside the tank, a rotor stator, and the end of the return pipe. The opening and closing of the large tank lid are automatic. The lid is also equipped with a drain valve and a vacuum break system. The large tank lid has a glass inspection port, a wiper, and a flashlight. The tank is also fitted with an inlet and outlet valve for washing and a nitrogen valve.
[0052] All components and subsystems of the device — including the mixers of both the small and large reservoirs, the homogenizer system, the cooling system of the large tank and the homogenizer pump and its outlet pipes, the heating element, the vacuum pump, and other electrical components — are controlled via a central electrical control panel (Fig. 3, No. 3). This control panel allows the operator to easily and precisely manage motor power, mixer speeds, homogenizer intensity, and heating element temperature. Additionally, this system is designed to be simple, safe, and monitorable, allowing for operational conditions to be controlled at any moment, as well as providing the ability to back up data.
[0053] To facilitate control over the amount of material inside the large reservoir, and based on the known diameter of the tank, each centimeter of its height corresponds to a specific volume. Therefore, the internal surface of the tank is graduated (Fig.
[0054] 4, No. 2), helping the operator to estimate the exact volume of materials in the tank at any given time. The optimal and standard working capacity of the tank, suitable for industrial and semi-industrial processes, is between 50 and 350 liters.For greater process flexibility, several auxiliary inlet and outlet ports are installed at the top of the large reservoir, each of which is controllable via dedicated valves. These valves are used for injecting inert gases (such as nitrogen) or various additives during the process. This feature allows necessary gases or additives to be introduced into the tank without interrupting the production process, thereby maintaining optimal conditions for nanoliposome formation. These inlets can also be used for sampling under specific conditions. Additionally, the return pipe for materials from the homogenizer to the large triple-walled (jacketted) tank is equipped with an inlet and outlet valve for cold water (4-8°C) to cool the circulating material.
[0055] The overall nanoliposome production process in this invention begins with the small reservoir. In the first step, the user pours the lipid phase components — such as phospholipids, cholesterol, or a mixture of lipids and other fat- soluble substances — into the small reservoir. At this stage, the low-speed mixer installed inside the tank is activated and gently mixes the lipid components uniformly to produce a homogeneous mixture ready for the next stage.
[0056] Once the lipid mixture is fully prepared, the operator opens the control valve located beneath the small reservoir. At this point, the lipid phase is gradually and controllably transferred through a stainless steel pipe into the larger reservoir. In the large reservoir, pre-prepared and preheated water is already present; therefore, upon the lipid components’ entry, the first stage of mixing immediately begins. Simultaneously with the entry of the lipid phase into the large reservoir, the homogenizer and bypass system are activated, and the components begin to circulate continuously within the system. At this stage, the homogenizer utilizes cavitation, shear stress, impact, and flow turbulence phenomena to break down thelipid phase particles into extremely fine (nanometric) sizes and uniformly disperse them within the aqueous phase. Moreover, the bypass system, by creating continuous fluid circulation, ensures that the mixture passes through the homogenizer multiple times, gradually forming a stable nanoliposomal structure. Ultimately, with the ongoing homogenization process and precise control of operational parameters such as temperature, pressure, and mixing speed, the final product is obtained in the form of a stable and uniform gel. Unlike dilute solutions, this gel-like product contains nanostructures with effective encapsulation, making it suitable for widespread applications in the pharmaceutical, cosmetic, and personal care industries. At the end of the process, the operator can discharge the final product from the tank and transfer it to the packaging stage or further processing.
[0057] The final product resulting from this process is a gel-like nanoliposomal composition that, due to its unique nature and relatively high viscosity, does not easily flow out of the tank like conventional liquids. In other words, although the product does not behave like a free-flowing liquid, it is still viscous enough to require positive and controlled pressure for rapid and complete discharge. As a result, gravity or passive drainage from the bottom outlet of the tank is insufficient, and a reliable and efficient discharge method is needed.
[0058] To this end, it is recommended to use a compressor or a positive pressure supply system to evacuate the product from the large reservoir. This system, by generating controlled air pressure above the gel surface, uniformly and completely drives the final product from the bottom outlet of the tank toward packaging lines or subsequent processing stages. The use of this method ensures that the product isdischarged quickly and cleanly, without compromising the structure of the nanoparticles and with minimal waste.
[0059] The specifications of the cavitation rotor and stator of the invention are as follows: The rotor-stator features 6 rows of blades and is protected against dust and moisture with an IP54 rating. The fluid head is designed for water by default, with a capacity of 5000 mmH20. The mechanical seal is made from Witon - Silicon, while the shaft is constructed from SS 316 L. Both the body and blades are also made from SS 316 L. The connection between the electric motor and the homogenizer is provided by an anodized aluminum flexible coupling. The pressure gauge has a range of 0-10 Bar, made of Wika SS 316 L, and the temperature gauge ranges from 0 to 120°C. The system is controlled by an 18.5 KW Pentax drive. The custom rotor-stator features 6-row blades with a jacket, specifically designed for the shear angles required for peptides and cosmetic and pharmaceutical nanomaterials. The jacket is machined with two O-rings on the housing. The diameter of the device body is 250 mm.
[0060] BRIEF DESCRIPTION OF THE FIGURES
[0061] Figure 1 shows a general view of the invention, which includes:
[0062] 1 : Manhole (Funnel)
[0063] 2: Wiper
[0064] 3 : Sodium lamp
[0065] 4: Automatic glass door
[0066] 5 : Large tank6: Small tank
[0067] 7 : Earthing system
[0068] 8: Water heating tank
[0069] 9: mixing motor
[0070] Figure 2 shows a side view of the large and small tanks, which includes:
[0071] 1 : Large tank thermometer
[0072] 2: Bypass pipe
[0073] Figure 3 shows a view of the large tank, which includes:
[0074] 1 : Vacuum pump
[0075] 2: Valve
[0076] 3 : Electrical panel
[0077] Figure 4 shows an internal view of the large tank, which includes:
[0078] 1 : mixer
[0079] 2: Graduated section
[0080] Figure 5 shows a top view of the large tank.
[0081] Figure 6 shows a view of the mixer of the large tank, which includes:
[0082] 1 : Motor
[0083] 2: mixer
[0084] 3: ScrubberFigure 7 shows a view of the lower section of the invention, which includes: 1 : Homogenizer
[0085] 2: Conical section of the large tank
[0086] 3 : Material transfer pipe
[0087] 4: Two-way valve
[0088] 5 : Conical section of the small tank
[0089] 6: Mixing motor of the small tank
[0090] Figure 8 shows a view of the small tank, which includes:
[0091] 1 : Electrical control panel
[0092] 2: Thermometer
[0093] 3: mixer
[0094] 4: Small tank
[0095] Figure 9 shows a view of the condenser and the steam collection tank, which includes:
[0096] 1 : Steam collection tank
[0097] 2: Condenser
[0098] Figure 10 shows a view of the heating tank related to the heating jacket, which includes:
[0099] 1 : Heating tank
[0100] 2: Heating element3 : Supply pipe
[0101] 4: Return pipe
[0102] Figure 11 shows an exploded view of the invention.
Claims
WHAT IS CLAIMED IS:
1. The invention of system and device for nanoliposome production using two separate reservoirs for lipid and aqueous components, equipped with a cavitational homogenizer system, comprising at least one small reservoir for mixing and homogenizing the lipid phase, at least one large reservoir for final homogenization and nanometric dispersion of particles in the aqueous phase, at least one cavitation homogenizer system for breaking down lipid phase particles to the nanoscale, at least one bypass system for continuous fluid circulation and enhanced homogenization, at least one advanced control system for precise regulation of temperature, pressure, and mixing speed, at least one vacuum pump for creating sealed conditions and preventing oxidation of sensitive substances, at least one heating and cooling jacket for temperature control of the reservoirs and pump, at least one dual-mode discharge system in the small reservoir for facilitating mixing and rapid process analysis, at least one glass lid for direct observation and monitoring of the process, at least one low-speed mixer inside the small reservoir, at least one axial (multi-blade) mixer inside the large reservoir, and at least one rod-type thermometer for measuring the temperature of the large reservoir.
2. The nanoliposome production system and device according to claim 1, wherein compounds such as phospholipids, cholesterol, or a mixture of lipids, loaded with peptides or plant extracts or vitamins or natural products or drugs, are combined in the small reservoir to form a uniform base for liposome formation.
3. The nanoliposome production system and device according to claim 1, wherein the homogenizer system is designed to break down particles to the nanometric scale using cavitation, shear stress, impact, and flow turbulence phenomena.
4. The nanoliposome production system and device according to claim 1, wherein the performance of the homogenizer depends on the material formulation, blade design, blade spacing, motor rotation speed, and internal pressure of its chamber.
5. The nanoliposome production system and device according to claim 1, wherein the bypass system is designed as a closed-loop circuit for continuous fluid circulation and repeated passage through the homogenizer, thereby enhancing homogenization and reducing particle size.
6. The nanoliposome production system and device according to claim 1, wherein the advanced control system precisely regulates temperature, pressure, and mixing speed to achieve optimal conditions for nanoliposome production.
7. The nanoliposome production system and device according to claim 1, wherein the small reservoir is conically shaped at its bottom to allow complete discharge of materials, ensuring no residue remains in the comers of the tank.
8. The nanoliposome production system and device according to claim 1, wherein all stainless steel components are made of SS 316 L and their interior surfaces are polished to a mirror finish to prevent corrosion and facilitate easy cleaning and sterilization of the device.
9. The nanoliposome production system and device according to claim 1, wherein the vacuum pump is used to create vacuum conditions within the reservoirs, prevent oxidation of sensitive materials, and improve the quality of the final product.
10. The nanoliposome production system and device according to claim 1, wherein the mixing speed in the small reservoir is adjustable based on the viscosity of the components to prevent the formation of excess air bubbles.
11. The nanoliposome production system and device according to claim 1, wherein the discharge of materials from the small reservoir to the largereservoir can be selected as either stepwise or continuous, depending on the process requirements.
12. The nanoliposome production system and device according to claim 1, wherein an axial mixer is used in the large reservoir to support uniform fluid circulation and prevent material sedimentation.
13. The nanoliposome production system and device according to claim 1, wherein the heating-cooling system in the large reservoir is used to regulate the temperature within the range of 4 to 70 degrees of Centigrade and create stable conditions for nanoliposome formation.
14. The nanoliposome production system and device according to claim 1, wherein a durable glass lid on the large reservoir, along with a wiper and flashlight, allows direct observation of the production process.
15. The nanoliposome production system and device according to claim 1, wherein sodium lamps are installed at the bottom of the reservoir to examine the appearance and clarity of the product.
16. The nanoliposome production system and device according to claim 1, wherein the central control system enables precise control of the homogenizer motor speed and adjustment of its performance intensity.
17. The nanoliposome production system and device according to claim 1, wherein the large reservoir is designed as a triple-walled structure to improve temperature control and ensure stable conditions during the production process.
18. The nanoliposome production system and device according to claim 1, wherein the return pipe from the homogenizer to the large reservoir is triplewalled (jacketed) and equipped with inlet and outlet valves for cold water, designed for effective cooling.
19. The nanoliposome production system and device according to claim 1, wherein the electrical panel and inverter provide programmable optionsincluding mixer speed, homogenizer motor speed, temperature control, and the ability to back up data.
20. The nanoliposome production system and device according to claim 1, wherein a vacuum pump and sealing system are used to prevent leakage and ensure optimal operation of the vacuum system.
21. The nanoliposome production system and device according to claim 1, wherein special blades are used in the rotor-stator of the homogenizer to enhance efficiency and speed in breaking down nanoliposomal particles.