TWM605096U - Foodstuff structure containing curcumin acid-base sensitive hydrogel crystal ball - Google Patents

Abstract

A food structure containing curcumin acid-base sensitive hydrocolloid crystal ball, which includes an outer membrane and a hydrocolloid crystal ball (CUR-Alg). This creation uses microemulsification (ME) to coat curcumin on two non-ionic surfactants, mixed lecithin (Lecithin) and polysorbate 80 (Tween80), and mixes it with soybean oil (oil phase) and water. The phase-formed microemulsion system (<100 nm) is then assembled with sodium alginate (Alg) based on calcium ion cross-linking and gelation as a curcumin-containing microemulsion-filled hydrogel. The hydrocolloid crystal balls constructed by mechanical peristaltic pumps have different release behaviors in acid-base environments. The results show curcumin in acidic environments at pH 1.2 (simulating gastric juice environment) and pH 7.5 (simulating intestinal juice environment). After 6 hours, the release rate is less than 30%; but in a slightly alkaline environment, the hydrogel ball is swelled and the release rate reaches more than 90% within 6 hours, forming an acid-base sensitive smart hydrogel crystal beads (about 3～5 mm), so that this creation can be used to develop water-soluble curcumin-containing oral preparations and health organic foods.

Description

Food structure of acid-base sensitive hydrocolloid crystal ball containing curcumin

This creation is about a food composition containing curcumin acid-base sensitive hydrocolloid crystal ball The structure, especially refers to a kind of acid-base sensitive smart hydrocolloid crystal beads with different release behavior under acid-base environment, especially refers to those that can be used to develop water-soluble curcumin-containing oral preparations and health organic foods.

The potential health benefits of many health ingredients have not been fully demonstrated in in vivo tests because It has been chemically degraded during product storage or in the process of ingestion into the gastrointestinal tract. In addition, many health ingredients have limited efficacy due to their insoluble properties, and poor stability and bioavailability (McClements et al., 2009). Therefore, it is necessary to develop a food-grade transportation system to coat and protect these health ingredients until they reach the proper part of the human body, such as the mouth, stomach, small intestine or colon (McClements, 2015; Shin et al., 2015). In recent years, in the field of health food, the development of smart hydrogel beads (hydrogel beads) formulations has considerable applicability, because transportation systems with special functions can be made of food-grade hydrocolloids.

The microemulsion system contains a mixture of water and oil phases and the interfacial activity that is compatible with water and oil phases The agent forms a thermodynamically stable homogeneous phase, optically isotropic solution. Since the droplets formed by the system are within the nanometer (nm) size range, the microemulsion solution is stable and clear. In recent years, the food industry has paid more and more attention to the application technology development of microemulsion technology to coat some insoluble functional ingredients or food additives in food formulations.

Curcumin is a yellow hydrophobic polyphenol pigment. Traditionally, turmeric has been used Treat skin wounds, inflammation and tumors. Curcumin has many activities, such as antioxidant, skin treatment Wounds, inflammation and tumors. Curcumin has a variety of activities, such as antioxidant, anti-inflammatory, antibacterial, anti-cancer, antioxidant, and hypolipidemic. In addition, curcumin has been widely known for its therapeutic applications in cancer, diabetes, cardiovascular disease, neurodegenerative diseases and gastrointestinal irritation. Human clinical trials have shown that curcumin is safe at high doses (12 g/day). Although the health benefits of curcumin have been confirmed, the full potential of curcumin has not been realized due to its low bioavailability.

In view of the foregoing, although curcumin has potential health benefits, the current Research is mainly in the pre-clinical stage, and only a few curcumin preparations have been commercialized in the past few decades. The problem is that curcumin has several serious shortcomings, including low water solubility, poor bioavailability after oral administration, and poor chemical stability under alkaline environment and ultraviolet radiation. Therefore, it is restricted not only in the food industry but also in the medical field. The direct application of curcumin. In addition, due to the short half-life of curcumin, its metabolism in the gastrointestinal tract is very rapid, so frequent administration is required to maintain effective blood drug concentration. Therefore, increasing the stability of curcumin and controlling the dissolution rate of the drug to prolong its residence time in the gastrointestinal tract is very important for improving the oral bioavailability of curcumin.

Previous studies have shown that curcumin has low water solubility and rapid elimination of metabolism, resulting in Bioavailability is poor, and various formulation techniques have been designed to improve the oral bioavailability of curcumin. For example, curcumin-loaded liposomes with an average particle size of 100-150 nm were prepared, and its activity was improved compared with free curcumin. In another study, curcumin liposomes caused a decrease in tumor growth. The self-microemulsifying drug delivery system of curcumin has higher solubility and higher bioavailability. In order to improve the efficiency of curcumin and have a variety of pharmacokinetics, various polymer nanoparticles have been prepared, including curcumin-coated poly(lactic-co-glycolic acid) (PLGA) ) And polyethylene glycol (PEG) to study the tissue distribution and blood-brain barrier penetration kinetics of PLGA nanoparticles loaded with curcumin. The micronized form of curcumin has significantly improved bioavailability. Design a curcumin-PEG complex and then encapsulate it with chitosan-gelatin nanoparticle, Can improve bioavailability. Recently, curcumin has been encapsulated to use supercritical antisolvent technology to extract It has high stability and solubility in water.

Compared with other delivery vehicles, hydrogels have been extensively studied due to their unique advantages, including better stability, high encapsulation efficiency, and the use of food-grade hydrocolloids (such as gelatin, starch, carrageenan, pectin and Alginate) is easy to manufacture. Due to the satisfactory properties of sodium alginate, such as non-toxicity, biocompatibility, biodegradability and environmental sensitivity, in the past two decades, people's interest in using sodium alginate for drug development has increased. Its structure is a natural polysaccharide, which is composed of (1→4) connected α-L-guluronic acid and β-D-mannuronic acid, which can quickly form a cross-linked network structure, so that in the presence of calcium ions (Ca ²⁺ ) form a hydrogel. Sodium alginate will form a gel under mild conditions, thereby preventing the inactivation of active substances (such as sensitive drugs, proteins, cells and enzymes). Previous studies filled the oil droplets in a three-dimensional solid (such as a hydrogel) to improve the stability of the emulsion. Food scientists have conducted studies on this combination, showing that carbohydrate hydrogels have been widely used as delivery systems, and have proven the stability of the active compound-loaded system. The coupling technology of the two structures provides the dual advantages of microemulsification and hydrogel. Previously, emulsion gels have been studied as hydrogel structure modifiers and controlled release.

In view of the various problems of learning skills, it is necessary to develop To develop an oral preparation and health-care organic food containing water-soluble curcumin.

The main purpose of this creation is to overcome the above-mentioned problems encountered by learning skills and Provides an acid-base sensitive smart hydrocolloid crystal beads with different release behaviors in an acid-base environment, which can be used to develop water-soluble curcumin-containing oral preparations and health organic foods containing curcumin acid-base sensitive hydrocolloid crystals The food structure of the ball.

Another purpose of this creation is to provide a simulated gastric juice acidity at pH 1.2 Under the environment, the release rate of curcumin after 6 hours is less than 30%, and under the slightly alkaline environment of simulated intestinal juice at pH 7.5 A food structure containing curcumin acid-base sensitive hydrogel crystal balls with a swelling shape and a curcumin release rate of over 90% after 6 hours.

In order to achieve the above purpose, this creation is a kind of acid-base sensitive hydrocolloid crystal ball containing curcumin The food structure includes: an outer membrane body with an accommodating space inside; and a hydrogel crystal ball (CUR-Alg) filled in the accommodating space of the outer membrane body, and the water gel The crystal ball system includes a curcumin-containing microemulsion layer (CUR-ME) and an adhesive film layer. The adhesive film layer covers the curcumin-containing microemulsion layer. The curcumin-containing microemulsion layer is composed of an oil phase, water The three-phase microemulsion composed of turmeric extract and nonionic surfactant constitutes a single uniform phase with light transmission, and the film layer is made of sodium alginate (Alg) cross-linked and gelled with calcium ions. As the basis, the hydrogel composed of the curcumin-containing microemulsion layer is coated to form hydrocolloid crystal spheres with a particle size of 3 to 5 mm.

In the above embodiments of this creation, the curcumin-containing microemulsion layer is microemulsified (ME) method to coat turmeric extract in mixed lecithin (Lecithin) and polysorbate 80 (Tween80) two non-ionic surfactants 1-100% (w/v) combined in proportion, and combined with Soybean oil is the oil phase 1-100% (w/v) and the water phase 1-100% (w/v), and the appropriate amount of soybean oil is mixed in proportion to form 100%. After shaking and mixing, a three-phase microemulsion (<100 nm) is formed. )By.

In the above-mentioned embodiment of this creation, after the film layer covers the curcumin-containing microemulsion layer The hydrocolloid crystal ball with a particle size of 3～5 mm is formed by mechanical peristaltic pump.

In the above-mentioned embodiment of this creation, the hydrocolloid spheres simulated the acidity of gastric juice at pH 1.2 Under the environment, the release rate of curcumin after 6 hours is less than 30%, and under the slightly alkaline environment of simulated intestinal juice at pH 7.5, the hydrocolloid crystal ball is swollen and the release rate of curcumin after 6 hours is more than 90%.

In the above embodiments of this creation, the food structure can be made into capsules, powders, tablets Or contained in the tank.

In the above embodiments of this creation, the food structure can be directly ingested or dissolved in the oral cavity. Oral preparations and health organic foods to be drunk in liquid.

In the above-mentioned embodiments of the present creation, the outer membrane system is a sugar-coated membrane.

In the above-mentioned embodiment of this creation, the outer membrane system is an edible capsule, including a glue The capsule and the lower capsule, and the upper capsule and the lower capsule are combined to form the containing space inside.

In the above-mentioned embodiment of this creation, the outer membrane system is the powder containing the accommodating space The powder package has a cutout preset on one side of the powder package, and the powder package can be made of paper or aluminum foil.

Please refer to "Pictures 1 to 5", which are the curcumin-containing works of this creation. Schematic diagram of the structure of acid-base sensitive hydrogel crystal ball, the schematic diagram of the food structure of the first preferred implementation of this creation, the schematic diagram of food structure of the second preferred implementation of this creation, and the acid-base sensitive hydrogel crystal ball created in different environments Schematic diagram, and schematic diagram of the appearance and release of the curcumin sodium alginate hydrocolloid spheres in this creation under different pH values. As shown in the picture: this creation is a food structure containing curcumin acid-base sensitive hydrogel crystal ball 1, which is composed of an outer membrane body 10 and a hydrocolloid crystal ball (CUR-Alg) 20.

An accommodating space 11 is provided in the outer membrane body 10 mentioned above.

The hydrogel crystal ball 20 is filled in the accommodating space 11 of the outer membrane body 10, and The hydrogel crystal ball 20 includes a curcumin-containing microemulsion layer (CUR-ME) 21 and an adhesive film layer 22. The adhesive film layer 22 covers the curcumin-containing microemulsion layer 21, and the curcumin-containing microemulsion layer 21 The latex layer 21 is a micro-emulsification (ME) method to coat the turmeric extract in a mixture of lecithin (Lecithin) and polysorbate 80 (Tween 80), two non-ionic surfactants combined in an appropriate ratio, 1-100% (W/v), and with soybean oil as oil phase 1-100% (w/v) and water phase 1-100% (w/v), proportionately doped with appropriate amount to form 100% and form after shaking and mixing Three-phase microemulsion (<100 nm) and the solution presents a single uniform phase with light transmission. The film layer 22 is a hydrogel composed of sodium alginate (Alg) and calcium ion cross-linked gelation as the basis to coat the curcumin-containing microemulsion layer 21, and then the particle size is formed by mechanical peristaltic pumping 3～5 mm hydrogel crystal ball 20. If so, a new food structure containing curcumin acid-base sensitive hydrocolloid crystal ball 1 is constructed by the above disclosed device.

When used, the food structure 1 mentioned in this creation can be made into capsules, powders, tablets Oral preparations and health-care organic foods that can be taken directly from the oral cavity or dissolved in a liquid to drink. In the first embodiment, as shown in Figure 2, the outer membrane body 10 is an edible capsule 10a, including an upper capsule 101a and a lower capsule 102a, and the upper capsule After 101a is combined with the lower capsule 102a, the containing space 11 is formed inside.

The hydrogel crystal ball 20 can be filled in the containing space 11 of the capsule 10a In order to control a single dose, the capsule 10a can be a hard capsule or a soft capsule, and can be a geometric capsule, which can be adjusted appropriately according to the packaging; when taking, the user can directly put the food structure 1a in the mouth , And swallow with warm water (or hot water), the gel film layer of the water gel crystal ball 20 22. It can have different release behaviors in acid-base environments, which can increase the stability of curcumin and control the dissolution rate of the drug to extend its residence time in the gastrointestinal tract, thereby increasing the oral bioavailability of curcumin.

In addition to the structure mentioned in the first embodiment, this creation can also be the second implementation The structure of the example, as shown in Figure 3, is different in that the outer membrane body 10 is a powder package 10b that includes the accommodating space 11, and has a pre-set in the powder package 11 Powder package 10b The cut 12b on the upper side of one side, and the powder pack 10b can be made of paper or aluminum foil.

The hydrocolloid crystal ball 20 series is sieved into a powder that can easily control a single dose. Individually packaged, or taken with health food, medicine or other beverages, and packed in the powder package In the accommodating space 11 of 10b, the powder can be in powder or granular form, which can be adjusted appropriately according to the packaging; when taking it, the user only needs to tear open the reserved cut 12b of the powder package 10b of the food structure 1b. It can be taken directly orally, or poured into a cup containing the solution and drank directly. In addition to achieving the above mentioned effects, it can also meet the needs of different usage states.

The following embodiments are only examples for understanding the details and connotation of this creation, but not for limitation The scope of patent application for the original creation.

[Preparation method of microemulsion] Under normal pressure, first mix the turmeric extract, oil phase and nonionic surfactant uniformly, and then add the water phase to prepare microemulsion. The detailed experimental steps are as follows: 1. Take the required oil phase, non-ionic surfactant and turmeric extract into the first test tube. 2. Take the required secondary water and put it in the second test tube. 3. Take 500 ml of the secondary water at 50°C and put it into the ultrasonic water bath, and turn on the Vortex Mixer. 4. Put the first test tube into the ultrasonic water bath and shake, and use the shaking mixer to stir to make the oil phase, the nonionic surfactant and the turmeric extract mix uniformly into a single homogeneous phase. 5. After the solution in the first test tube is uniformly mixed, add the secondary water in the second test tube into the first test tube. 6. Finally, put the first test tube into the ultrasonic water bath and use the ultrasonic vibration test tube, during which the first test tube is stirred with the vibration mixer until the solution presents a single uniform phase with light transmission.

[Preparation of Sodium Alginate Hydrogel Crystal Ball] Take 2.0 g of sodium alginate, add 50 mL of distilled water, heat the mixture over water, and stir for 2 hours. Add the right amount of ginger The yellow extract is added to the sodium alginate solution by direct mixing or microemulsion, and stirred at room temperature for 2 hours to make it completely dispersed and dissolved in the sodium alginate solution, and then the preparation of the hydrocolloid crystal ball can be started. Mix 28 g of anhydrous calcium chloride with 1000 mL of distilled water in a beaker and pour it into a deep plastic box. Take out the mechanical peristaltic pump, drive the roller to roll the peristaltic tube at a speed of rpm 5 to generate vacuum suction, and drop the sodium alginate-curcumin mixed solution directly from the tube into a 2.8% calcium chloride solution plastic box. In the process of dropping, use a glass rod and stir at a slow speed to shape the sodium alginate-curcumin mixed water colloidal crystal ball without sticking together. Soak the sodium alginate-curcumin hydrogel crystal ball for 60 minutes to take it out, and wash it several times with distilled water. Use SMS Texture Analyser to measure the hardness of hydrocolloid crystal balls prepared with different formulations as a reference index for formula optimization. In addition, the hydrocolloid crystal balls are freeze-dried and compared with the previous hydrocolloid crystal balls. Compare the physical and chemical properties, swelling degree and controlled release.

[Controlled release of curcumin] Soak 100 mg of sodium alginate-curcumin hydrocolloid spheres in 50 ml of simulated gastric fluid with or without pepsin (SGF) and pH 6.8 simulated colonic fluid at 37°C. with or without pectinase, SCF), simulated intestinal fluid with or without pancreatin (SIF) with pH 7.4, or multi-frequency ultrasonic waves, changing different frequencies or energy ultrasonic waves, and taking a quantitative solution at intervals to After the ethyl acetate is extracted twice, it is concentrated under reduced pressure and re-dissolved in a suitable alcohol solvent. The absorbance value is measured in a 426 nm ultraviolet (UV) spectrophotometer, and the UV absorbance value is converted into a concentration and then plotted. The release rate calculation formula is as follows: Release rate (%)=×100%

Figure 4 shows the acid-base sensitive smart hydrogel crystal ball in different environments. Middle A represents the hydrocolloid spheres containing curcumin microemulsion layer at pH 1.2 acidic environment, B represents the hydrocolloid spheres containing curcumin microemulsion layer at pH 7.4 slightly alkaline environment, and C represents the direct mixing of curcumin at pH 1.2 Acidic environment, D represents the direct incorporation of curcumin in a slightly alkaline environment at pH 7.4. This creation uses calcium ions as a cross-linking agent to prepare coated curcumin sodium alginate hydrocolloid crystal balls, and compares the appearance diameter, swelling degree and release rate under different pH values. The results show that the hydrocolloid spheres containing curcumin microemulsion layer have the best swelling degree in a pH 7.4 environment compared with the swelling degree in a pH 1.2 environment (3 mm) (5 mm).

Figure 5 shows the appearance of hydrocolloid spheres containing curcumin sodium alginate at different pH values. In the release situation, the curve of the diamond data point in the figure represents the hydrogel crystal ball containing the curcumin microemulsion layer at pH 1.2 acidic environment, and the curve of the square data point represents the hydrogel crystal ball containing the curcumin microemulsion layer at pH 7.4 slightly alkaline Environment, the curve with triangular data points represents the direct incorporation of curcumin in an acidic environment at pH 1.2, and the curve with x-shaped data points represents the direct incorporation of curcumin in a slightly alkaline environment at pH 7.4. The above-mentioned hydrocolloid spheres containing turmeric extract have different release behaviors in acid-base environments. Under the acidic environment of simulated gastric juice at pH 1.2, the release rate of curcumin after 6 hours is less than 30%; but the simulated intestinal juice at pH 7.5 is slightly alkaline Under the environment, the hydrogel crystal ball is swelling and the curcumin release rate reaches more than 90% after 6 hours, forming an acid-base sensitive intelligent hydrogel crystal ball.

It can be seen from the above that this creation uses microemulsification technology to coat curcumin in mixed lecithin Fat and Tween80 two non-ionic surfactants, and a micro-emulsion system (< 100 nm) formed with soybean oil (oil phase) and water phase, and then combined with sodium alginate based on calcium ion cross-linking and gelation. Assembled hydrogel filled with curcumin microemulsion. The hydrocolloid crystal balls constructed by mechanical peristaltic pumps have different release behaviors in acid-base environments. The results show curcumin in acidic environments at pH 1.2 (simulating gastric juice environment) and pH 7.5 (simulating intestinal juice environment). After 6 hours, the release rate is less than 30%; but in a slightly alkaline environment, the hydrogel ball is swelled and the release rate reaches more than 90% within 6 hours, forming an acid-base sensitive smart hydrogel crystal beads (about 3～5 mm), so that this creation can be used to develop water-soluble curcumin-containing oral preparations and health organic foods.

In summary, this creation is a food containing curcumin acid-base sensitive hydrogel crystal ball The structure can effectively improve the various shortcomings of conventional use. It has different release behaviors in acid-base environments. Under the acidic environment of simulated gastric juice at pH 1.2, the release rate of curcumin after 6 hours is less than 30%, and the simulated intestinal juice at pH 7.5 is slightly alkaline Under the environment, the hydrogel crystal ball is swelling and the curcumin release rate is greater than 90% after 6 hours, forming an acid-base sensitive smart hydrogel crystal ball (about 3 ~ 5 mm), which can be used to develop water Oral preparations of soluble curcumin and health-care organic foods make the creation of this creation more advanced, more practical, and more in line with the needs of users. It has indeed met the requirements of a new patent application, and a patent application has been filed in accordance with the law.

However, the above are only the preferred embodiments of this creation, and should not be limited to this The scope of implementation of this creation is determined; therefore, everything made in accordance with the scope of the patent application for this creation and the content of the new specification The simple equivalent changes and modifications should still fall within the scope of this creation patent.

1. 1a, 1b: Food structure 10: Outer membrane body 10a: Capsule 101a: Upper capsule 102a: Lower capsule 10b: Powder package 11: Housing space 12b: Incision 20: Hydrogel crystal ball 21: Curcumin-containing microemulsion layer 22: Film layer

Figure 1 is a schematic diagram of the structure of the curcumin-containing acid-base sensitive hydrocolloid crystal ball of this creation. Figure 2 is a schematic diagram of the food structure of the first preferred implementation of this creation. Figure 3 is a schematic diagram of the food structure of the second preferred implementation of this creation. Figure 4 is a schematic diagram of the acid-base sensitive hydrogel crystal ball created in different environments. Figure 5 is a schematic diagram of the appearance and release of hydrocolloid spheres containing curcumin sodium alginate under different pH values.

1.1a: Food structure

10: Outer membrane body

10a: capsule

101a: Upper capsule

102a: Lower capsule

10b: Powder packet

11: Housing space

12b: incision

20: Hydrogel crystal ball

21: Containing curcumin microemulsion layer

22: Film layer

Claims (9)

A food structure containing curcumin acid-base sensitive hydrocolloid crystal balls, including: An outer membrane body with an accommodation space inside; and A water colloidal crystal ball (CUR-Alg) is filled in the accommodating space of the outer film body, and the water colloidal crystal ball includes a curcumin-containing microemulsion layer (CUR-ME) and an adhesive film layer , The film layer coats the curcumin-containing microemulsion layer, the curcumin-containing microemulsion layer is composed of an oil phase, an aqueous phase, and a three-phase microemulsion solution composed of turmeric extract and nonionic surfactant It is a light-transmitting single uniform phase, and the film layer is composed of a hydrogel composed of sodium alginate (Alg) and calcium ion cross-linked gelation as a basis to coat the curcumin-containing microemulsion layer with a particle size of 3～ 5 mm hydrogel crystal ball. According to the food structure containing curcumin acid-base sensitive hydrocolloid crystal ball according to the first item of the scope of patent application, the curcumin-containing microemulsion layer is a microemulsion (ME) method to coat the turmeric extract in the mixture Lecithin (Lecithin) and polysorbate 80 (Tween80) two non-ionic surfactants 1-100% (w/v) combined in proportion, and 1-100% (w/v) in oil phase with soybean oil v) and water phase 1～100% (w/v), doped with appropriate amount in proportion to form 100%, and form three-phase microemulsion (<100 nm) after shaking and mixing. According to the food structure of the curcumin acid-base sensitive hydrogel crystal ball described in item 1 of the scope of patent application, the curcumin-containing microemulsion layer is coated with the curcumin-containing microemulsion layer and then the granule is formed by mechanical peristaltic pumping. Hydrogel crystal ball with diameter of 3～5 mm. The food structure containing curcumin acid-base sensitive hydrocolloid spheres according to item 1 of the scope of patent application, wherein the hydrocolloid spheres have a 6-hour release rate of curcumin under the acidic environment of simulated gastric juice at pH 1.2 30%, and in a simulated intestinal fluid slightly alkaline environment with pH 7.5, the hydrocolloid crystal ball is swelling and the curcumin release rate is more than 90% after 6 hours. The acid-base sensitive hydrocolloid crystal ball containing curcumin as described in item 1 of the scope of patent application The food structure, wherein the food structure can be made into any one of capsule, powder, lozenge or contained in a can. The food structure containing curcumin acid-base sensitive hydrocolloid crystal ball according to the first item of the scope of patent application, wherein the food structure is an oral preparation that can be taken directly by the oral cavity or dissolved in a liquid and drunk. food. According to the food structure of the curcumin acid-base sensitive hydrocolloid crystal ball described in item 1 of the scope of patent application, the outer film system is a sugar-coated film. According to the food structure containing curcumin acid-base sensitive hydrocolloid crystal ball described in item 1 of the scope of patent application, the outer membrane system is an edible capsule, including an upper capsule and a lower capsule, and the upper capsule and the lower capsule The accommodating space is formed inside the capsule after being combined. According to the food structure containing curcumin acid-base sensitive hydrocolloid crystal ball according to item 1 of the scope of patent application, the outer membrane system is a powder package containing the accommodating space, which has a preset in the powder The upper side of the bag is cut, and the powder bag can be made of paper or aluminum foil.

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