Method and apparatus for providing a frozen composition

Abstract

This disclosure generally relates to a method and apparatus for providing a frozen composition, and more specifically, to a method and apparatus for spraying a composition in a frozen state onto a target area. A composition in a liquid state is sprayed together with a refrigerant, and the composition is frozen into a solid state by the refrigerant having a relatively low temperature and reaches the target area. The composition in a solid state has an improved skin penetration effect compared to a composition in a liquid state.

Description

Technical Field

[0001] Cross - reference to Related Applications This application claims priority to Korean Patent Application No. 10 - 2023 - 0053940, filed on April 25, 2023, the entire content of which is incorporated herein by reference for all purposes. The present disclosure generally relates to a method and an apparatus for providing a frozen composition, and more specifically, to a method and an apparatus for injecting a composition in a frozen state into a target area.

Background Art

[0002] When delivering a composition to the skin, the degree to which the composition penetrates the skin has a significant impact on the degree of the effect caused by the composition. Therefore, various studies have been conducted to improve the penetration ability of the composition into the skin.

[0003] Methods for delivering a composition to the skin include applying the composition to the skin, injecting the composition into the skin, or spraying the composition onto the skin.

[0004] Among these, applying a composition to the skin makes it difficult for the composition to pass through the lipid layer of the skin depending on its molecular weight and biochemical properties, and as a result, only a very small amount is known to be absorbed by the skin.

[0005] In addition, injecting a composition into the skin enables the composition to penetrate deep into the skin, but inevitably damages the skin. This causes not only pain during the procedure but also problems such as purpura or swelling due to damage to the skin. Furthermore, injecting a composition into the skin requires the skill of an operator, so the penetration depth and amount can vary depending on the operator. This is disadvantageous in that the effect of the composition may not be consistent.

[0006] Therefore, a composition delivery method is needed that minimizes damage to the skin while ensuring the ability of the composition to penetrate the skin and inducing a consistent penetration effect. [Overview of the Initiative]

[0007] One objective is to enable the composition to reach depths beneath the epidermis of the skin.

[0008] Another objective is to allow the composition to reach depths below the stratum corneum of the skin.

[0009] Another objective is to allow the composition to reach the dermis of the skin.

[0010] Another objective is to freeze a composition that is in a liquid state at room temperature and to provide the composition to the skin in a solid state.

[0011] Another purpose is to spray the composition onto the skin, where the freezing rate of the composition reaching the skin is equal to or greater than a predetermined value.

[0012] Another objective is to freeze the composition into particles of a predetermined size or smaller, and then apply the frozen composition to the skin.

[0013] Another objective is to deliver the frozen composition to the skin at a rate equal to or greater than a predetermined rate.

[0014] Another objective is to provide a composition that maintains the skin at a predetermined temperature or within a predetermined range.

[0015] The purposes of this disclosure are not limited to those mentioned above, and any other purposes not mentioned will be clearly understood by those skilled in the art from the following description and accompanying drawings.

[0016] According to one embodiment, a method is provided for freezing and spraying a composition, the method comprising: preparing a mixed spray system configured to spray a refrigerant and a composition, the mixed spray system comprising a nozzle configured to spray the refrigerant and a composition guide arranged adjacent to the nozzle; positioning the mixed spray system at a distance from a target area, where the opening of the nozzle of the mixed spray system is the outlet from which the refrigerant is sprayed, and the opening is positioned toward the target area; spraying the composition together with the refrigerant into the target area by using the mixed spray system, the nozzle forming a refrigerant spray stream, and the composition guide guiding the liquid composition to be introduced into the refrigerant spray stream, a portion of the liquid composition being frozen and reaching the target area as a solid composition; wherein, at one point in time when the refrigerant and composition are sprayed through the mixed spray system, the freezing rate, which represents the ratio of the solid composition to the liquid composition in the observation area, is greater than or equal to 5%, where the observation area is defined as an area of ​​arbitrary width in a side view of the mixed spray system, at an observation distance from the nozzle opening, where the observation distance corresponds to the distance between the nozzle opening and the target area.

[0017] According to one embodiment, a freeze-injection system is provided for freezing and injecting a composition, the freeze-injection system comprising: a refrigerant container in which a refrigerant is stored at a pressure between 10 bar and 1000 bar; a refrigerant receiving unit configured to receive the refrigerant from the refrigerant container; a nozzle having an opening of a predetermined size and configured to inject the refrigerant, the nozzle pressurizing the refrigerant passing through it, thereby causing the refrigerant passing through the nozzle to expand to atmospheric pressure, and as a result the temperature of the refrigerant to drop; a composition container containing the composition; a composition guide fluidically connected to the composition container and configured to discharge the composition, the end of which is aligned adjacent to the nozzle, thereby introducing the composition into the refrigerant stream injected from the nozzle; a valve positioned between the refrigerant receiving unit and the nozzle and configured to control the flow of refrigerant from the refrigerant receiving unit to the nozzle; and a controller configured to control the valve; wherein, when the refrigerant and composition are injected from the freeze-injection system, the freezing rate, which represents the ratio of the solid state of the composition to the liquid state of the composition, is greater than or equal to 5% at a time point in an observation area, where the observation area is located at an observation distance from the nozzle opening and has an arbitrary width.

[0018] The means for solving the problem are not limited to those described above, and solutions not mentioned can be clearly understood by those skilled in the art from this specification and the accompanying drawings.

[0019] According to one embodiment, it is possible to allow the composition to reach a depth below the epidermis of the skin.

[0020] According to another embodiment, the frozen composition can be made to reach the skin surface.

[0021] According to another embodiment, it is possible to control the degree to which the composition reaches the skin surface freezes.

[0022] According to another embodiment, it is possible to increase the amount of composition that penetrates the skin compared to the amount of composition provided to the skin surface.

Brief Description of Drawings

[0023] The effects of the present disclosure are not limited to those mentioned above, and other effects not mentioned will be clearly understood by those skilled in the art from the following description and the accompanying drawings. [Figure 1] It is a schematic diagram showing a hybrid injection system according to an embodiment. [Figure 2] It is a diagram showing how the composition is frozen and injected according to an embodiment. [Figure 3] It is a diagram showing how the freezing rate of the composition is determined using an observation region according to an embodiment. [Figure 4] It is an image of a scene where the composition in a liquid state and the composition in a solid state are injected according to an embodiment. [Figure 5] It is an image of a scene where the composition in a liquid state and the composition in a solid state are injected according to an embodiment. [Figure 6] It is a diagram showing an image processing process for counting solid composition particles according to an embodiment. [Figure 7] It is a diagram showing how the freezing rate is calculated using an observation line according to an embodiment. [Figure 8] It is a diagram showing a hybrid injection system according to an embodiment. [Figure 9] It is a diagram showing components of a refrigerant injection device according to an embodiment. [Figure 10] It is a diagram showing a composition supply device according to an embodiment. [Figure 11] It is a diagram showing a composition supply device according to another embodiment. [Figure 12] It is a flowchart showing a freezing injection method according to an embodiment. [Figure 13] It is a diagram showing the results of a first experiment for confirming the penetration effect depending on freezing and the penetration effect depending on the freezing rate. [Figure 14]This figure illustrates the results of the first experiment, which confirmed the penetration effect dependent on freezing and the penetration effect dependent on the freezing rate. [Figure 15] This figure illustrates the results of the second experiment, which confirmed the penetration effect dependent on the freezing rate. [Figure 16] This figure illustrates the penetration effect of test group 1 and test group 5 in the second experiment. [Figure 17] This diagram illustrates the relationship between particle size and injection velocity according to the embodiment. [Figure 18] This figure illustrates the results of an experiment to confirm the penetration effect, which depends on the temperature of the skin surface. [Modes for carrying out the invention]

[0024] According to one embodiment, a method is provided for freezing and spraying a composition, the method comprising: preparing a mixed spray system configured to spray a refrigerant and a composition, the mixed spray system comprising a nozzle configured to spray the refrigerant and a composition guide arranged adjacent to the nozzle; positioning the mixed spray system at a distance from a target area, where the opening of the nozzle of the mixed spray system is the outlet from which the refrigerant is sprayed, and the opening is positioned toward the target area; spraying the composition together with the refrigerant into the target area by using the mixed spray system, the nozzle forming a refrigerant spray stream, and the composition guide guiding the liquid composition to be introduced into the refrigerant spray stream, a portion of the liquid composition being frozen and reaching the target area as a solid composition; wherein, at one point in time when the refrigerant and composition are sprayed through the mixed spray system, the freezing rate, which represents the ratio of the solid composition to the liquid composition in the observation area, is greater than or equal to 5%, where the observation area is defined as an area of ​​arbitrary width in a side view of the mixed spray system, at an observation distance from the nozzle opening, where the observation distance corresponds to the distance between the nozzle opening and the target area.

[0025] The observation area is defined in the side view of the mixing injection system by a first line that is perpendicular to the central axis of the nozzle and is located a distance from the nozzle opening by the observation distance, and by a second line that is parallel to the first line and is located at an arbitrary distance from the first line.

[0026] The observation distance is within the recommended injection distance range determined for the mixed injection system.

[0027] The freezing rate is the ratio of the number of particles in the solid state of the composition to the sum of the number of particles in the liquid state and the number of particles in the solid state of the composition in the observation area at time point 1.

[0028] The freezing rate is 17% or greater.

[0029] The rate at which the solid composition reaches the target region is 50 m / s or greater.

[0030] The average size of the solid-state composition present in the observation area is between 20 μm and 60 μm.

[0031] According to one embodiment, a freeze-injection system is provided for freezing and injecting a composition, the freeze-injection system comprising: a refrigerant container in which a refrigerant is stored at a pressure between 10 bar and 1000 bar; a refrigerant receiving unit configured to receive the refrigerant from the refrigerant container; a nozzle having an opening of a predetermined size and configured to inject the refrigerant, the nozzle pressurizing the refrigerant passing through it, thereby causing the refrigerant passing through the nozzle to expand to atmospheric pressure, and as a result the temperature of the refrigerant to drop; a composition container containing the composition; a composition guide fluidically connected to the composition container and configured to discharge the composition, the end of which is aligned adjacent to the nozzle, thereby introducing the composition into the refrigerant stream injected from the nozzle; a valve positioned between the refrigerant receiving unit and the nozzle and configured to control the flow of refrigerant from the refrigerant receiving unit to the nozzle; and a controller configured to control the valve; wherein, when the refrigerant and composition are injected from the freeze-injection system, the freezing rate, which represents the ratio of the solid state of the composition to the liquid state of the composition, is greater than or equal to 5% at a time point in an observation area, where the observation area is located at an observation distance from the nozzle opening and has an arbitrary width.

[0032] The observation area is defined in the side view of the freeze-injection system by a first line that is perpendicular to the central axis of the nozzle and is located at an observation distance from the nozzle opening, and by a second line that is parallel to the first line and is located at an arbitrary distance from the first line.

[0033] The observation distance is within the recommended injection distance range determined for the mixed injection system.

[0034] The freeze-injection system further comprises a heat generating unit installed between the refrigerant receiving unit and the nozzle, configured to heat at least a portion of the refrigerant moving from the refrigerant receiving unit to the nozzle, wherein the controller is configured to heat the refrigerant by using the heat generating unit, thereby achieving a freeze rate of 5% or greater.

[0035] The controller is configured to apply power within a predetermined power range to a heat generating unit, which generates thermal energy to be transferred to the refrigerant, where the predetermined power range is set so that the freezing rate is 5% or greater.

[0036] The freezing rate is the ratio of the number of particles in the solid state of the composition to the sum of the number of particles in the liquid state and the number of particles in the solid state of the composition in the observation area at time point 1.

[0037] The freeze-injection system further includes an actuator connected to the composition container and configured to supply the composition to a composition guide.

[0038] The composition guide includes an input end into which the composition flows and an output end into which the composition is discharged, wherein the output end of the composition guide is located within a predetermined distance from the end of the nozzle.

[0039] The purposes, features, and characteristics of this disclosure will be more clearly understood from the following detailed description in conjunction with the accompanying drawings. However, this disclosure can be embodied in many different forms and should not be limited to exemplary embodiments. Embodiments will be referred to in more detail hereafter, and specific examples thereof are illustrated in the accompanying drawings.

[0040] In the drawings, the thickness of layers and regions is emphasized for clarity. Furthermore, when an element or layer is referred to as "on" or "above" another element or layer, it may be directly on the other element or layer, or an intervening element or layer may exist between them. As a general rule, similar reference numerals designate similar elements throughout the specification. In addition, similar reference numerals are used to designate elements having the same function within the same concept as illustrated in the drawings of each embodiment, and redundant descriptions are omitted.

[0041] The numbers used in this specification (e.g., 1st, 2nd, etc.) are simply identifiers used to distinguish one element from another.

[0042] In addition, the element suffixes "module" and "part" used in the following embodiments are given solely for the purpose of facilitating the drafting of the specification, or are mixed together with them, and do not have any meaning or role that distinguishes them from one another by themselves.

[0043] In this specification, the singular forms "a," "an," and "the" are intended to include the plural form unless the context explicitly indicates otherwise.

[0044] In the following embodiments, as used herein, terms such as “equipment,” “includes,” and “have” specify the presence of the mentioned feature or element, but do not exclude the presence or addition of one or more other features or elements.

[0045] In drawings, the size of elements may be emphasized or reduced for illustrative purposes. For example, the size and thickness of elements in drawings are shown arbitrarily for illustrative purposes, and embodiments of this disclosure are not limited thereto.

[0046] When some exemplary embodiments can be embodied in other ways, certain process steps described herein can be performed in other ways. That is, for example, two process steps described in a sequential order can be performed substantially simultaneously or in reverse order.

[0047] In the following embodiments, when membranes, regions, elements, etc. are said to be connected to one another, they can be directly connected or indirectly connected to one or more intervening membranes, regions, elements, etc. sandwiched between them.

[0048] For example, when membranes, regions, elements, etc. are said to be electrically connected to one another, they can be electrically directly connected to one another, or they can be electrically indirectly connected to one another with one or more intervening membranes, regions, elements, etc. sandwiched between them.

[0049] In the following embodiments, when membranes, regions, elements, etc., are said to be fluidly connected to one another, it can be understood that they may form at least a portion of the flow path through which each fluid flows.

[0050] For example, when we say that element A is fluidically connected to element B, it may mean that a fluid passing through a channel formed by element A can reach a channel formed by element B, or vice versa. Specifically, when elements A and B are connected and the channels formed by element A and element B are directly connected to each other, elements A and B can be considered fluidly connected. Otherwise, when elements A and B are connected to each other through an element C such as a conduit, and as a result the channels formed by element A and element B are indirectly connected to each other through the channel formed by element C, elements A and B can be considered fluidly connected. Here, element C can be understood as fluidly connecting elements A and B. Furthermore, elements A and B can be fluidly connected to each other through multiple elements.

[0051] Unless otherwise specified or evident from the context, the term “about” as used herein in relation to a number or range of numbers is understood to mean the number stated and its ±10 percent, or 10 percent below the enumerated lower limit and 10 percent above the enumerated upper limit for any range of values.

[0052] This disclosure generally relates to a freeze-injection method and apparatus for providing a frozen composition, and more specifically to a method and apparatus for injecting a composition in a frozen state into a target area.

[0053] The composition may contain active substances that induce or produce medical effects. Alternatively, the composition may contain active substances that induce or produce cosmetic effects.

[0054] Furthermore, the compositions of this disclosure are particularly characterized by transdermal delivery, where a composition may refer to a substance that produces a cosmetic or medical effect during transdermal delivery.

[0055] The composition may include, for example, minerals, nucleic acids, amino acids, coenzymes, vitamins, niacinamide, oil-soluble licorice extract, arbutin, hyaluronic acid, potassium hyaluronate, hydrolyzed hyaluronic acid, hydrolyzed sodium hyaluronate, hydroxypropyltrimonium hyaluronate, sodium acetylated hyaluronate, sodium hyaluronate crosspolymer, sodium hyaluronate, retinol, retinyl palmitate, adenosine, peptides, coenzyme Q10, adult stem cells, antioxidants, poly-d-lactic acid (PDLA), polynucleotides, polydeoxyribonucleotides (PDRN), poly-d,l-lactic acid (PDLLA), lidocaine, botulinum toxin, exosomes, propalacin, tetracaine, human growth hormone, growth factors, cell therapy products, or combinations thereof.

[0056] Furthermore, the composition may further contain base components such as purified water, glycerin, butylene glycol, propanediol, and silicone oil; formulation-producing components such as emulsifiers, surfactants, and viscosity modifiers; and preservative components such as parabens, phenoxyethanol, benzoic acid, triclosan, benzyl alcohol, methylisothiazolinone, and 1,2-hexanediol.

[0057] In this disclosure, the use of a transfer medium as a method for spraying a composition. For example, the composition may be sprayed at a relatively high speed and held in place by a coolant sprayed over a target area. In this case, the temperature of the composition may be lowered by a coolant sprayed at a relatively low temperature.

[0058] Here, the refrigerant may be liquefied carbon dioxide (CO2), carbon dioxide, liquefied nitrogen, liquefied oxygen, nitrogen dioxide (NO2), nitric oxide (NO), nitrous oxide (N2O), hydrofluorocarbon (HFC) materials, methane (CH4), perfluorocarbon (PFC), sulfur hexafluoride (SF6), or a combination thereof. Materials that can apply cooling energy to the target region, such as refrigerants and cooling gases, may be used. On the other hand, compressed air may be used in addition to the refrigerant.

[0059] Hereafter, for the sake of explanation, the composition will be described as being held by a refrigerant, with liquefied carbon dioxide being used as the refrigerant, but the technical concept of this disclosure is not limited thereto.

[0060] Freezing a composition means that a composition in a liquid or gaseous state transitions to a solid state as its temperature decreases. As the temperature decreases, the composition transitions to a solid composition with crystals. The freeze-injection method described in this disclosure can be understood as a method of freezing and injecting a liquid composition so that the solid composition is injected onto a target area.

[0061] In this disclosure, the target area refers to an area to which the composition needs to be sprayed. Specifically, the target area may refer to the skin surface of a part of the human body. Alternatively, the target area may refer to the skin surface of a part of the body of an animal other than a human. The target area may be determined depending on the body part to which the composition is provided.

[0062] The freeze-injection method described herein has a variety of applications, including the following:

[0063] Cryo-spraying can be used as a therapeutic method or medical procedure. Here, "composition" may refer to a drug or pharmaceutical and may be understood to include substances used for the diagnosis, cure, alleviation, treatment or prevention of disease or disorder, skin regeneration, lifting, and treatment of problems such as acne and inflammation.

[0064] A physician or other healthcare professional (as defined in the medical laws of each country as a person with medical expertise) may use a cryo-spray method to spray a composition that has a therapeutic effect on a particular disorder or disease onto the person being treated.

[0065] The freeze-spray method can be used as a cosmetic treatment, cosmetic procedure, or skincare method. Here, "composition" refers to a cosmetic product and can be understood to include substances that, when applied to the skin, induce cosmetic effects such as whitening, skin soothing, nourishing, moisturizing, wrinkle reduction, or elasticity improvement. Furthermore, the composition may consist of substances that have little to no effect on the human body.

[0066] An esthetician or skincare professional may use a freeze-spray method to spray a composition with cosmetic effects onto the person being treated.

[0067] Freeze spraying can be used as a therapeutic or cosmetic treatment for animals other than humans. Here, "composition" refers to a drug, pharmaceutical, or cosmetic product that contains an active substance having a therapeutic or cosmetic effect.

[0068] 1. Regarding the penetration of the composition

[0069] The primary objective of the freeze-spray method described herein is to enable the composition to penetrate the skin.

[0070] 1.1 Meaning and Importance of Composition Penetration

[0071] Composition penetration means that the composition reaches a specific depth from the skin surface. More specifically, composition penetration means that the composition reaches a depth below the epidermis of the skin.

[0072] The epidermis is composed of the stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, and stratum basale. In particular, the stratum corneum functions as a skin barrier and is the main factor that prevents the absorption of compositions.

[0073] Therefore, penetration of the composition means that the composition reaches at least below the stratum corneum. Since the thickness of the stratum corneum is approximately 10 μm to 20 μm, penetration of the composition means that the composition reaches a depth of approximately equal to or greater than 0.01 mm from the skin surface.

[0074] For example, when the target of providing the composition is the face of an adult in Korea, the epidermis is distributed to a depth of approximately 0.1 mm from the skin surface, and the dermis is distributed to a depth of approximately 0.1 mm to approximately 2 mm from the skin surface.

[0075] When we say that the composition penetrates the face, it means that the composition penetrates to a depth of approximately 0.01 mm to 2 mm, approximately 0.02 mm to 2 mm, approximately 0.1 mm to 2 mm, approximately 0.2 mm to 2 mm, approximately 0.3 mm to 2 mm, approximately 0.4 mm to 2 mm, approximately 0.5 mm to 2 mm, approximately 0.6 mm to 2 mm, approximately 0.7 mm to 2 mm, and approximately 0.8 mm to 2 mm. This means reaching a depth of approximately 0.9 mm to 2 mm, 1 mm to 2 mm, 1.1 mm to 2 mm, 1.2 mm to 2 mm, 1.3 mm to 2 mm, 1.4 mm to 2 mm, 1.5 mm to 2 mm, 1.6 mm to 2 mm, 1.7 mm to 2 mm, 1.8 mm to 2 mm, or 1.9 mm to 2 mm. Since the thickness of the epidermis and dermis can vary depending on the area of ​​the face, the reference depth defining the penetration of the composition is not limited to the above values.

[0076] On the other hand, the target to which the composition is sprayed is not limited to the face; other body parts besides the face may be targeted, such as the scalp, neck, arms, legs, hands, and feet. Here, penetration of the composition also means that the composition reaches below the stratum corneum or epidermis of each body part.

[0077] For a composition to achieve its purpose (e.g., to induce therapeutic or cosmetic effects), it is crucial that it is absorbed into the skin. For a composition to be absorbed into the skin, it needs to penetrate beyond the stratum corneum and spread to the basal layer or dermis. In other words, even if a composition contains highly effective active substances, if it remains in the stratum corneum of the skin, its effects will inevitably be minimal.

[0078] There are three main ways in which a composition can penetrate the dermis through the epidermis of the skin. These include transcellular pathways that pass directly through the stratum corneum of the epidermis, intracellular pathways that pass through the nonpolar lipid layer between keratinocytes, and transadnexal pathways that pass through appendages such as pores.

[0079] However, since appendages occupy only 0.1% of the skin's surface area, the amount of penetration through them is limited. Therefore, penetration through intercellular or intracellular pathways is more important than through the appendage pathway.

[0080] 1.2 Conventional composition penetration methods and problems

[0081] Conventional methods for penetrating a composition into the skin include topical application methods, injection methods using a syringe, needling methods that create holes in the skin with microneedles after applying the composition, and spraying methods that spray the composition in the form of fine particles.

[0082] Application methods, which involve applying a composition to the skin surface, allow the composition to penetrate through intercellular or intracellular pathways. However, even when the applied composition passes through the stratum corneum via transcellular pathways, it is blocked by the granular layer of the epidermis, and therefore has difficulty passing through the spinous or basal layer, resulting in difficulty for the composition to reach the dermis. Even when the composition passes through the stratum corneum via intracellular pathways, the amount of composition that passes through is very small, so the amount of composition that reaches the dermis is insufficient.

[0083] Syringe injection is an invasive method of delivering a composition by inserting a syringe into the dermis or subcutaneous tissue. Compared to other penetration methods, syringe injection is problematic because it is relatively painful and the composition is introduced concentratedly into one area of ​​the skin, rather than spreading evenly across the skin. In addition, with syringes, the location where the composition is introduced into the skin varies depending on the extent to which the syringe is inserted into the skin. Since the total thickness of the epidermis and dermis is approximately 2 mm, accurately inserting the syringe into the dermis depends on the skill level of the operator, and therefore, consistent therapeutic effects may not be guaranteed.

[0084] Needling involves applying a composition to the skin and creating holes in the skin using a needling device equipped with multiple microneedles having a micro-level length, allowing the composition to penetrate through the holes.

[0085] In the needling method, microneedles are inserted into the skin to which the composition is applied, or the composition penetrates the skin through holes formed by the microneedles. Due to the thickness of the microneedles, the holes formed in the skin are also shallow, and therefore the amount of composition introduced through the holes is limited.

[0086] In addition, the needling method can be painful depending on the size of the needle in the needling device, and since the skin is damaged when the needling device creates holes in the skin, additional care is needed to heal the skin damage after the composition has penetrated. Furthermore, disinfection before use is essential to prevent infection caused by the needle in the needling device.

[0087] The airbrush method uses compressed air as a delivery medium and a fine nozzle 1500 to atomize the composition into relatively small particles and spray them onto the skin. The airbrush method is a non-invasive, painless, and easy-to-use method for delivering compositions. However, in the case of the airbrush method, the composition collides with the skin surface in a liquid state, making it difficult to provide an impact strong enough to physically penetrate the epidermis. As a result, in the airbrush method, the composition passes through the stratum corneum via intercellular or intracellular pathways, but, as with topical application methods, it is difficult for the composition to pass through the stratum spinosum or basal layer of the epidermis.

[0088] 1.3 Method for delivering compositions using refrigerants

[0089] As a method for penetrating a composition into the skin, this disclosure describes a method using a mixing and spraying system 100.

[0090] Figure 1 is a schematic diagram illustrating a mixed injection system 100 according to an embodiment.

[0091] The mixed injection system 100 employs a method of injecting a composition using a refrigerant. Referring to Figure 1, the mixed injection system 100 may include a refrigerant injection device 1000 and a composition supply device 2000.

[0092] The refrigerant injection device 1000 refers to a device that injects refrigerant. The refrigerant injection device 1000 includes at least a refrigerant container RC through which the refrigerant is stored, a flow control unit 1200 that controls the movement of the refrigerant so that it is either injected or not injected from the refrigerant injection device 1000, and a nozzle 1500 through which the refrigerant is injected. In addition to those described above, the refrigerant injection device 1000 may further include other components necessary for its operation. Additional components of the refrigerant injection device 1000 will be described later.

[0093] The composition supply device 2000 refers to a device that provides a composition. The composition supply device 2000 may include a composition container CC for storing the composition and a composition guide 2100 for discharging the composition. The composition guide 2100 may include an input terminal through which the composition stored in the composition container CC is introduced, and an output terminal through which the composition is discharged. In addition to those described above, the composition supply device 2000 may include other components necessary for operation. Additional components of the composition supply device 2000 will be described later.

[0094] The composition supply device 2000 is connected to the refrigerant injection device 1000 and can supply the composition to the refrigerant injected from the refrigerant injection device 1000. Specifically, the nozzle 1500 of the refrigerant injection device 1000 can form a refrigerant injection stream, and the composition guide 2100 of the composition supply device 2000 can be installed adjacent to the nozzle 1500.

[0095] Here, the refrigerant injection stream refers to the flow of refrigerant containing refrigerant particles injected from the nozzle 1500. The refrigerant injection stream formed by the nozzle 1500 may create a negative pressure at the output end of the composition guide 2100, which may allow the composition to move along the composition guide 2100 and be introduced into the refrigerant injection stream. Alternatively, the composition supply device 2000 may include an actuator 2200 fluidly connected to the composition container CC. The composition may be supplied to the composition guide 2100 at a predetermined flow rate, or at a flow rate within a predetermined range by the actuator 2200, and introduced into the refrigerant injection stream.

[0096] The composition introduced into the refrigerant injection stream can collide with and be ejected together with the refrigerant particles in the refrigerant injection stream. The composition in the refrigerant injection stream can be broken down into small particles by the high velocity of the refrigerant injection stream and cooled by heat exchange with the refrigerant injection stream, which has a relatively low temperature. Thus, the composition and the refrigerant can be mixed and ejected in the mixed injection system 100.

[0097] On the other hand, the internal pressure of the refrigerant container RC in which the refrigerant is stored can be approximately 10 bar to approximately 1000 bar at room temperature. Alternatively, the internal pressure of the refrigerant container RC can be approximately 30 bar to approximately 200 bar at room temperature. Alternatively, the internal pressure of the refrigerant container RC can be approximately 50 bar at room temperature. The internal pressure of the refrigerant container RC can relate to the rate at which the refrigerant expands when it is discharged from the nozzle 1500 of the refrigerant injector 1000. In other words, as the internal pressure of the refrigerant container RC increases, the velocity of the refrigerant particles in the refrigerant injection stream can increase. Considering that the pressure of the compressed air used in the above airbrush method is approximately 1 bar to approximately 5 bar, using a high-pressure refrigerant as a transfer medium can significantly increase the injection velocity of the composition, thereby improving the penetration effect of the composition.

[0098] However, even after reviewing various existing literature, it is not known that a composition can effectively penetrate the skin when the state of the composition reaching the skin surface is controlled using the mixing and spraying system 100. In particular, it is not known that a composition can effectively penetrate the skin when it reaches the skin surface in a "frozen" state.

[0099] There is a history of experiments suggesting that spraying carbon dioxide and the composition together has an effect on reducing cellulite. However, this is interpreted as a cooling effect due to carbon dioxide and does not reveal that a larger amount of the composition "reaches" fat cells, so it does not provide an indicator that a relatively large amount of the composition penetrates the skin.

[0100] In the process of developing the mixed injection system 100, the applicant conducted experiments to determine the extent to which the composition penetrates the skin when the composition and refrigerant are injected together, and confirmed that the composition penetrated the skin more effectively compared to conventional methods. An investigation into the reason for this revealed that the improved penetration effect was not simply due to the composition being injected together with the refrigerant, but also because the composition was injected in a frozen state.

[0101] More specifically, while observing the process of injecting both the composition and the refrigerant in the mixed injection system 100, the applicant confirmed that a portion of the composition, which was in a liquid state before being frozen by the refrigerant, collided with the skin surface in a solid state.

[0102] Figure 2 is a diagram illustrating how the composition is frozen and sprayed according to an embodiment. Referring to Figure 2, when the refrigerant spray stream RSS is formed by the nozzle 1500, the composition is discharged in a liquid state from the composition guide 2100 and introduced into the refrigerant spray stream RSS. As the liquid composition is sprayed along the refrigerant spray stream RSS, it transitions into solid frozen particles, which reach the skin surface.

[0103] The applicant assumed that the fact that the composition is frozen by the refrigerant and becomes frozen particles is a factor that affects the penetration ability of the composition, and improved the mixed injection system 100 for frozen injection while conducting experiments on frozen injection, as will be described later.

[0104] 2. Method of freezing and spraying the composition

[0105] 2.1 About Freeze Spray

[0106] Freeze spraying means that a frozen composition collides with the skin surface in such a way that the composition has a significant penetrating effect on the skin.

[0107] Significant penetration effect means that the composition penetrates the skin to a predetermined level or greater. In addition, significant penetration effect means that the composition penetrates deeply into the skin.

[0108] More specifically, significant penetration effect means that when the composition is frozen and sprayed onto the skin surface, the amount of the composition that reaches below the epidermis of the skin is equal to or greater than a predetermined level compared to the amount of composition sprayed.

[0109] Alternatively, when the same amount of composition is mixed with a refrigerant sprayed at the same rate and applied to the skin surface, the penetration effect may be more pronounced when the amount of composition that penetrates is greater compared to when the composition is applied to the skin surface in an unfrozen state.

[0110] Alternatively, significant penetration effect means that when the composition is frozen and sprayed onto the skin surface, at least a portion of the composition reaches below the epidermis of the skin.

[0111] When a composition is applied to the skin surface by freezing spray, it is expected to penetrate the epidermis more easily. This is because, when the composition is frozen and collides with the skin surface in the form of a solid composition, the impact force is expected to be greater than that of a liquid composition.

[0112] Specifically, when liquid composition particles and solid composition particles having the same momentum (mass × velocity) collide with the skin surface, the harder solid composition particles exert a greater impact force due to their shorter collision time, and as a result, can pass through the stratum corneum more easily.

[0113] In addition, since solid composition particles are crystalline solids, their impact area with the skin surface may be smaller than that of liquid composition particles. Therefore, solid composition particles have a greater impact force per unit area and can pass through the stratum corneum more easily than liquid composition particles.

[0114] The fact that the frozen composition penetrates the stratum corneum can be understood as the frozen particles of the composition forming holes on the skin surface and penetrating the basal layer of the epidermis or the dermis below it. Since the frozen composition acts as needles, the cryo-spray method can be called the needling method.

[0115] 2.3 Freeze spray with improved penetration effect

[0116] As explained above, freeze spraying means bringing a frozen composition into contact with the skin surface so that the composition has a significant penetrating effect on the skin.

[0117] On the other hand, as will be described later, the applicant conducted experiments on frozen spraying and confirmed that when the degree to which the composition was frozen reached a predetermined level, the penetration effect of the composition improved compared to when the composition was sprayed in an unfrozen state.

[0118] More specifically, it was investigated whether the penetration of the composition improved when the temperature of the refrigerant injection stream was adjusted so that the composition traveled in a frozen state until it reached the skin surface, and as a result, it was confirmed that the penetration effect of the composition improved. The first experiment relating to this will be described later.

[0119] In addition, it was necessary to confirm how the penetration effect of the composition varies depending on the degree to which it is frozen when it reaches the skin surface. The applicant conducted experiments to confirm this, along with a second experiment described later, and before that, established an objective standard for the degree to which the composition was frozen in the freeze spray.

[0120] Here, a method was used to determine the degree to which the composition was frozen by calculating and evaluating the freezing rate when the mixing injection system 100 is viewed from the side (e.g., left or right). Here, the state of viewing the mixing injection system 100 from the side means the state of viewing the mixing injection system 100 from the left or right when it is operating normally. For example, the image shown in Figure 4 is an image of the mixing injection system 100 viewed from the right side. The method for calculating the freezing rate and the method for designing the mixing injection system 100 to control the freezing rate will be described later.

[0121] First, when viewing the mixed spraying system 100 performing the freeze spray from the side, the penetration effect is higher when the freezing rate is 17% (with a measurement error of 5% or less, approximately 12% to 22%) than when the freezing rate is substantially 0%. Therefore, when the composition is sprayed onto the skin surface with a freezing rate of 17%, the penetration effect of the composition is significant, and sprays with the corresponding freezing rate can be understood as freeze sprays.

[0122] In addition, when the mixed spraying system 100 performing the freeze spray is viewed from the side, the penetration effect is higher when the freezing rate is 5% (with a measurement error of less than 1%, approximately 4% to 6%) than when the freezing rate is substantially 0%. Therefore, when the composition is sprayed onto the skin surface with a freezing rate of 5%, the penetration effect of the composition is significant, and sprays with the corresponding freezing rate can be understood as freeze sprays.

[0123] In addition, it was confirmed that the penetration effect of the composition improved as the freezing rate of the composition that reached the skin surface increased. Specifically, the penetration effect improved in the following order: when the freezing rate of the composition was 5% (within a 1% measurement error, approximately 4% to 6%), when the freezing rate of the composition was 17% (within a 5% measurement error, approximately 12% to 22%), when the freezing rate of the composition was 48% (within a 3% measurement error, approximately 45% to 51%), when the freezing rate of the composition was 71% (within a 3% measurement error, approximately 68% to 74%), and when the freezing rate of the composition was 100% (within a 1% measurement error, approximately 99% to 100%).

[0124] In other words, when the penetration effect is improved under the condition that the composition's freezing rate is 5%, a high penetration effect can also be achieved when the composition's freezing rate is equal to or greater than 5%. Therefore, the composition's freezing rate can be adjusted from 5% to 100%. Alternatively, the composition's freezing rate can be adjusted from 5% to 17%. Alternatively, the composition's freezing rate can be adjusted from 5% to 48%. Alternatively, the composition's freezing rate can be adjusted from 5% to 71%.

[0125] Considering the measurement error range, the freezing rate of the composition can be adjusted from 2% to 100%. Alternatively, the freezing rate of the composition can be adjusted from 2% to 22%. Alternatively, the freezing rate of the composition can be adjusted from 2% to 51%. Alternatively, the freezing rate of the composition can be adjusted from 2% to 74%.

[0126] On the other hand, in the process of increasing the freezing rate of the composition, it was confirmed that the penetration effect of the composition decreased when the skin surface was excessively cooled by the refrigerant or the composition. More specifically, even when the freezing rate of the composition that reached the skin surface was high, the decrease in skin surface temperature could cause penetration-inhibiting substances such as an ice film to form, thereby preventing the composition from reaching the skin surface. In this case, the penetration effect of the composition may decrease. Therefore, it is necessary to design the mixing and spraying system 100 considering the increase in the freezing rate of the composition while maintaining the skin surface temperature at or above an appropriate temperature, and specific design methods will be described later.

[0127] As in the example above, the freezing rate is calculated when the mixed injection system 100 performing the freeze-injection is viewed from the side. When the penetration effect is higher than when the freezing rate is 0%, the composition is frozen and injected at a freezing rate equal to or higher than the calculated freezing rate. This can be understood as freeze-injection.

[0128] The method for calculating the freezing rate will be explained below with reference to Figures 3 to 6.

[0129] Figure 3 illustrates how the freezing rate of the composition is determined using the observation region OR according to an embodiment. Figure 3(a) illustrates that the observation region OR is specified based on the mixing injection system 100, and Figures 3(b) and 3(c) illustrate the cases where the freezing rate in the observation region OR is different, respectively.

[0130] 2.3.1 Calculation of the freezing rate of the composition in the observation area

[0131] A high-speed camera may be used as a means of observing the freezing injection. Specifically, when the mixed injection system 100 injects the refrigerant and the composition, the refrigerant injection stream RSS into which the composition is introduced can be photographed using a high-speed camera. Images or videos clearly captured using the high-speed camera show the form in which the composition is injected at a given time or over a given period of time, and the degree to which the composition is frozen can be determined through the images or videos.

[0132] The observation area OR may be designated for observing freezing jets. The observation area OR may refer to the area for determining the freezing rate.

[0133] Specifying an observation area OR is to determine the freezing rate of the composition that reaches the skin surface. When a composition is sprayed with a refrigerant, the composition may freeze in any region within the refrigerant spray stream RSS. However, since the purpose of freeze spraying is to penetrate the composition into the skin, it is desirable to determine whether the composition that actually reaches the skin surface is frozen, or to determine the proportion of the composition that is frozen. In other words, considering that the purpose of freeze spraying is to determine the freezing rate that affects the penetration effect of the composition, it is desirable to observe the region adjacent to the skin surface during freeze spraying, rather than observing the entire region in which the composition can be frozen.

[0134] The observation area OR may be designated based on the location corresponding to the skin surface to which the composition needs to be sprayed. For example, referring to Figure 3(a), when the composition is sprayed onto the skin surface by the mixing spray system 100, the area that is separated from the opening of the nozzle 1500 of the mixing spray system 100 by a distance corresponding to the separation distance between the opening of the nozzle 1500 and the skin surface when the mixing spray system 100 is viewed from the side may be designated as the observation area OR.

[0135] More specifically, when the mixing injection system 100 is viewed from the left or right, a hypothetical first line L1 can be determined that is perpendicular to the central axis CA of the nozzle 1500 and is located at an observation distance OD away from the opening of the nozzle 1500 of the mixing injection system 100. In addition, when the mixing injection system 100 is viewed from the left or right, a second line L2 can be determined that is parallel to the first line L1 and is located at an observation width OW in the direction toward the nozzle 1500 (or away from the nozzle 1500). The observation region OR can be determined as the region between the first line L1 and the second line L2.

[0136] The observation distance OD may be determined based on the recommended spray distance. Alternatively, the observation distance OD may be determined based on the ends of the distance maintenance unit, which will be described later. Alternatively, the observation distance OD may be determined based on the length of the distance maintenance unit.

[0137] Here, the recommended spray distance may refer to the distance at which the mixing spray system 100 needs to be positioned relative to the skin surface during use. Specifically, the recommended spray distance may refer to the preferred straight-line distance between the nozzle 1500 and the skin surface when operating the mixing spray system 100 to spray the refrigerant and composition onto the skin surface. The recommended spray distance may be determined differently depending on the specifications of the components of the mixing spray system 100 (e.g., the internal pressure of the refrigerant container RC, the size of the opening of the nozzle 1500, etc.).

[0138] The recommended spray distance is preferably longer than the length of the acceleration section required to accelerate the composition. Specifically, the composition is frozen after being introduced into the refrigerant injection stream RSS, and the frozen composition is accelerated over a predetermined section. To sufficiently accelerate the frozen particles of the composition, an acceleration section of a predetermined length in a direction parallel to the central axis CA of the nozzle 1500 is required. For example, to sufficiently accelerate the frozen particles of the composition, an acceleration section of about 3 mm to about 5 mm or about 1 mm to about 10 mm is required. It is preferable that the acceleration section is ensured based on the position where the composition is introduced into the refrigerant injection stream RSS. Therefore, the recommended spray distance can be set to be greater than the sum of the distance from the opening of the nozzle 1500 to the position where the composition is introduced into the refrigerant injection stream RSS, and the length of the acceleration section, based on a direction parallel to the central axis CA of the nozzle 1500.

[0139] The recommended spray distance is preferably longer than the length of the acceleration section required to accelerate the composition.

[0140] In addition, the recommended spray distance is preferably longer than the length of the freezing section required for the composition to be introduced into the refrigerant injection stream RSS and frozen.

[0141] The recommended spray distance may be selected, for example, within the range of 3 mm to 100 mm. On the other hand, since the recommended spray distance is a guide to a preferred spray distance, it may be presented as a range rather than a specific value. For example, the recommended spray distance may be presented as a range with a lower limit and an upper limit for the distance selected within the range of 3 mm to 100 mm.

[0142] The observation distance OD may be the same as the recommended spray distance. When the observation distance OD is the same as the recommended spray distance, the area where the skin surface is expected to be located may be designated as the observation area OR.

[0143] On the other hand, the observation distance OD may be shorter than the recommended spray distance. When the process of spraying the composition and refrigerant onto the skin surface is filmed with a high-speed camera, it is difficult to determine the freezing rate of the composition on the skin surface. Therefore, the freezing rate determined at a predetermined distance from the skin surface can be estimated as the freezing rate of the skin surface. In this case, the observation distance OD may be shorter than the recommended spray distance. Alternatively, when the mixing spray system 100 is viewed from the side, the observation area R can be determined by a first straight line L1 located a first distance away from the skin surface, and a second straight line L2 parallel to the first straight line L1 and located a distance of observation width OW away from the first straight line L1.

[0144] The observation distance OD may be set greater than the recommended spray distance. In this case as well, the freezing rate in the observation area OR can be estimated as the freezing rate of the skin surface.

[0145] When the recommended spray distance is presented as a range, the observation distance OD may fall within the recommended spray distance range. The recommended spray distance range may be determined as an interval between 3 mm and 100 mm.

[0146] On the other hand, the observation distance OD does not necessarily have to be determined based on the recommended spray distance and can be determined arbitrarily.

[0147] The observation distance OD can be set greater than the minimum threshold distance value. Since heat exchange must occur between the refrigerant and the composition for the composition to be introduced into the refrigerant injection stream RSS and frozen, this heat exchange takes a predetermined amount of time. Because the composition is moved by the refrigerant during heat exchange, it may not freeze in the area closest to the nozzle 1500 through which the refrigerant is injected. Therefore, considering that an observation area OR is set to observe frozen particles, the observation distance OD can be set greater than the distance corresponding to the area closest to the nozzle 1500. For example, the observation distance OD can be set greater than the minimum threshold distance value determined within the range of 0 mm to 3 mm.

[0148] The observation width OW refers to the width of the observation area OR.

[0149] The observation width OW can be determined within the range of 1% to 50% of the observation distance OD. Alternatively, the observation width OW can be determined as the diameter of the refrigerant injection stream RSS at a distance of observation distance OD from the opening of nozzle 1500. Alternatively, the observation width OW can be determined as the average diameter of the refrigerant injection stream RSS. On the other hand, the observation width OW may not be specified as an arbitrary value, and the observation area OR may be the interior of the refrigerant injection stream RSS visible to the naked eye.

[0150] The freezing rate can be defined as the ratio of the number of solid composition particles to the sum of the number of solid composition particles and liquid composition particles in a particular region. For example, referring to Figure 3(b) or Figure 3(c), the freezing rate can be obtained by counting the number of solid composition particles and liquid composition particles observed in the observation region OR and dividing the number of solid composition particles by the sum of the number of solid composition particles and liquid composition particles.

[0151] On the other hand, the freezing rate may take into account the number of gaseous composition particles. However, it is difficult to calculate the number of gaseous composition particles, and when the refrigerant and composition are injected together, the majority of the composition exists in a solid or liquid state, so it is preferable that the freezing rate does not take into account the number of gaseous composition particles.

[0152] Hereafter, with reference to Figures 4 to 6, a method for identifying solid composition particles in captured images will be explained.

[0153] Figures 4 and 5 are images of the liquid and solid compositions being sprayed according to the embodiment. Figure 4 shows an image taken by a high-speed camera while light is radiating towards the mixing injection system 100 that sprays the composition and refrigerant. Figure 5 shows an image of the mixing injection system 100 that sprays the composition and refrigerant, taken by a high-speed camera, where light is radiating towards the high-speed camera and blocked by the composition.

[0154] Figure 6 illustrates an image processing process for counting solid composition particles according to an embodiment. Figure 6(a) shows an image of the observation region OR, Figure 6(b) shows an image obtained by applying a threshold filter to the image in Figure 6(a), and Figure 6(c) shows the tracking of solid composition particles in the image in Figure 6(b).

[0155] In calculating the freezing rate, solid composition particles and liquid composition particles can be visually distinguished in high-speed camera images or videos (hereinafter referred to as "images," etc.). Specifically, referring to Figure 4, since solid composition particles have a crystalline form, they reflect light and appear relatively bright.

[0156] Therefore, among the particles that are visually identifiable in images captured by high-speed cameras, particles that reflect light and appear bright may be designated as solid composition particles, while particles that do not reflect light and appear dark may be designated as liquid composition particles.

[0157] In addition, as illustrated in Figure 5, liquid composition particles and solid composition particles can be distinguished based on the brightness of the composition particles in images captured by a high-speed camera, etc. Referring to Figure 5, since solid composition particles are darker than liquid composition particles, solid composition particles and liquid composition particles can be identified based on predetermined levels of brightness.

[0158] Referring to Figure 6, solid composition particles can be counted by separating an observation region OR from an image captured by a high-speed camera, applying a filter to the observation region OR that selects pixels with a brightness equal to or less than a predetermined level of brightness, and tracking pixels that occupy more than the predetermined area.

[0159] In addition to the methods described above for identifying solid composition particles, dynamic light scattering (DLS) using polarization analysis, time-resolved X-ray diffraction (TR-XRD), or in situ spectroscopy may be used.

[0160] On the other hand, the freezing rate can be defined as the ratio of the area of ​​solid composition particles to the sum of the area of ​​solid composition particles and liquid composition particles in a specified region.

[0161] According to the embodiment, the freezing rate can be calculated using the following method.

[0162] First, while the composition and refrigerant are injected together by the mixing injection system 100, an image can be acquired using a high-speed camera. Next, an observation area OR can be specified in the acquired image, and the freezing rate can be calculated in the specified observation area OR.

[0163] Multiple images can be obtained here.

[0164] For example, the mixed injection system 100 may perform a freeze injection n times (where n is a natural number equal to or greater than 2), and in the freeze injection process of the nth trial, an image of the nth trial may be taken at a predetermined time after the start of the injection. Subsequently, the freeze rate of the nth trial may be calculated from the image of the nth trial, and the average of the freeze rates of the first trial to the nth trial may be obtained as the final freeze rate. Here, performing a freeze injection n times can be understood as performing the injection of the composition and refrigerant n times, with the same amount of refrigerant stored in the refrigerant container RC at the same pressure and the same amount of composition stored in the composition container CC.

[0165] In another example, the refrigerant and composition may be sprayed from a mixed injection system 100 during a preset imaging time, and at least two or more images may be obtained from the images acquired during the imaging time. An observation area OR may be specified, the freezing rate may be calculated from each image acquired, and the average of each freezing rate for each image acquired may be obtained as the final freezing rate.

[0166] On the other hand, when multiple images are acquired, the freezing rate can be calculated by averaging the freezing rates acquired in each image, as well as by adding the number of solid composition particles and liquid composition particles counted in each image.

[0167] As explained below, the penetration effect of the composition may vary depending on the freezing rate. For example, the penetration effect of the composition may increase as the freezing rate increases.

[0168] Therefore, the mixed injection system 100 needs to be designed so that the freezing rate at which a significant penetration effect of the composition is achieved is known, and the freezing injection is performed at the corresponding freezing rate.

[0169] As explained above, the calculation of the freezing rate in the observation region OR is understood as freezing injection, but the technical concept of this disclosure is not limited thereto.

[0170] For example, when the composition and refrigerant are sprayed together, if the number of frozen particles in the observation area OR is equal to or greater than a preset threshold number of particles, this can be understood as a freeze spray.

[0171] Here, the threshold particle number is the value at which the composition's penetration effect on the skin is higher than when the number of frozen particles is substantially zero, and can be determined through experimentation.

[0172] On the other hand, the method for counting the number of frozen particles in the observation area OR is the same as the method for counting the number of frozen particles in the composition among the methods for calculating the freezing rate described above.

[0173] Above, a method for calculating the freezing rate was described by specifying an observation area OR when viewing the mixing injection system 100 or the injection of the composition and refrigerant from the side. However, the technical concept of the present disclosure is not limited thereto, and it is also possible to calculate the freezing rate by specifying an observation area OR when viewing the mixing injection system 100 or the injection of the composition and refrigerant from above or below. Furthermore, it is also possible to calculate the freezing rate by counting solid composition particles and liquid composition particles when viewed from two or more directions.

[0174] Similarly, when viewed from directions other than the side, or from two or more directions, a freezing rate with a significant penetration effect can be calculated through experimentation, and spraying the composition and refrigerant at a freezing rate equal to or greater than the corresponding freezing rate can be understood as a freeze spray.

[0175] 2.3.2 Calculation of the freezing rate of the composition passing through the observation line

[0176] The freezing rate can be calculated based on the observation line OL, as described below.

[0177] Figure 7 illustrates how the freezing rate is calculated using the observation line OL according to the embodiment. Figure 7(a) illustrates that the observation line OL is specified based on the mixing injection system 100, and Figure 7(b) illustrates the composition particles passing through the observation line OL at first and second time points.

[0178] The observation line OL may be specified based on the position corresponding to the skin surface to which the composition needs to be sprayed. For example, referring to Figure 6(a), when viewing the mixing spray system 100 that sprays the composition from the side, a straight line at a predetermined distance from the mixing spray system 100 may be specified as the observation line OL. More specifically, when viewing the mixing spray system 100 from the left or right side, a hypothetical straight line perpendicular to the central axis CA of the nozzle 1500, at an observation distance OD from the opening of the nozzle 1500 of the mixing spray system 100, may be determined as the observation line OL.

[0179] Here, the observation distance OD is the same as that described in the observation area OR.

[0180] The freezing rate can be calculated as the ratio of the number of frozen particles of the composition to the sum of the number of solid and liquid composition particles that pass through the observation line OL over a predetermined period of time. More specifically, referring to Figure 7(b), the freezing rate can be calculated in the following manner. First, an image can be acquired by photographing the side of the mixing injection system 100 that injects the composition using a high-speed camera. Next, an image frame corresponding to a random first time point and an image frame corresponding to a second time point can be selected from the image. Finally, in the selected image frames, the number of liquid and solid composition particles that have passed through the observation line OL from the first time point to the second time point can be counted.

[0181] The freezing rate can be obtained as the average of the individual freezing rates acquired for multiple images. Here, the multiple images may include images acquired from each of the freezing injection processes of the nth trial. Here, the multiple images may refer to images acquired during n periods of images acquired by photographing the injection of composition and refrigerant from the mixed injection system 100 over a predetermined period.

[0182] As described in the observation area OR, the method of calculating the freezing rate using the observation line OL may also assume that the mixing injection system 100 is viewed from above, below, or two or more directions, and from the side.

[0183] 2.3.3 Calculation of the freezing rate of the composition sprayed onto the observation surface

[0184] The freezing rate can be calculated using the observed surface, as described below.

[0185] First, the observation surface may be positioned in the mixing and spraying system 100 at a distance of observation distance OD, and the composition and refrigerant may be sprayed onto the observation surface while the high-speed camera is photographing the observation surface.

[0186] Subsequently, an image frame corresponding to the time when the composition first reaches the observation surface, or a predetermined period thereafter, can be obtained from the images captured by the high-speed camera.

[0187] Solid compositions and liquid compositions can be distinguished based on the difference in color (or brightness) on the observation surface of the acquired image frame, and therefore, the area occupied by the solid composition and the area occupied by the liquid composition can be calculated based on the observation surface.

[0188] The freezing rate can be calculated as the ratio of the area occupied by the solid composition to the sum of the area occupied by the solid composition and the area occupied by the liquid composition.

[0189] In a method for calculating the freezing rate using an observation surface, sensors that distinguish between liquids and solids may be used in addition to a high-speed camera. For example, the temperature change of an insulating plate may be monitored while the composition and refrigerant are being injected onto the insulating plate, and the freezing rate may be calculated based on the change in the temperature of the insulating plate, or the amount of cooling energy (or heat) required to maintain the temperature, and the latent heat absorbed by the freezing particles when they transition to a liquid state. In another example, an electrical contact sensor may be placed on the observation surface, and the freezing rate may be estimated based on the change in the measured electrical signal, taking into account the capacitance when the liquid and solid compositions are in contact with the observation surface.

[0190] An electrical contact sensor is used in a method for calculating the freezing rate using an observed surface.

[0191] 2.4 Method for generating frozen particles

[0192] Hereafter, a method for generating frozen particles by freezing the composition will be described with reference to Figures 8 to 11.

[0193] As described above, frozen particles of the composition can be generated using the mixing injection system 100. Specifically, a refrigerant injection stream RSS having a relatively low temperature can be formed by the refrigerant injection device 1000 of the mixing injection system 100, and frozen particles can be generated while the composition is supplied to the refrigerant injection stream RSS by the composition supply device 2000 of the mixing injection system 100.

[0194] Figure 8 is a diagram illustrating a mixed injection system 100 according to an embodiment. Referring to Figure 8, the mixed injection system 100 may include a refrigerant injection device 1000 and a composition supply device 2000. The composition supply device 2000 may be connected to the nozzle 1500 of the refrigerant injection device 1000.

[0195] On the other hand, as shown in Figure 8, the mixing injection system 100 may further include a cover COV that covers the nozzle 1500 and supports the composition supply device 2000.

[0196] Hereafter, for the sake of explanation, the composition supply device 2000 will be described as being connected to the nozzle 1500 of the refrigerant injection device 1000, but the technical concept of this disclosure is not limited thereto. In addition to the nozzle 1500, the composition supply device 2000 may be connected to the cover COV or the housing of the refrigerant injection device 1000. However, even in this case, the composition guide 2100 of the composition supply device 2000 must be installed adjacent to the nozzle 1500 of the refrigerant injection device 1000 so that the composition discharged from the composition guide 2100 is introduced into the refrigerant injection stream RSS formed at the nozzle 1500.

[0197] 2.4.1 Detailed Components of the Mixing Injection System

[0198] Figure 9 is a diagram illustrating the components of a refrigerant injection device 1000 according to an embodiment. Referring to Figure 9, the refrigerant injection device 1000 may include a container receiving unit 1100, a flow adjustment unit 1200, a heat generation unit 1300, a nozzle connecting unit 1400, a nozzle 1500, a sensor unit 1600, an input unit 1700, an output unit 1800, and a controller 1900.

[0199] The container receiving unit 1100 can accommodate a refrigerant container RC. The container receiving unit 1100 includes a refrigerant receiving section into which the refrigerant is introduced. The refrigerant receiving section can be understood as a component including a flow path or hole for the movement of the refrigerant.

[0200] For example, the refrigerant container RC may be provided as a portable cartridge, and the refrigerant container RC may be mounted on or removed from a container receiving unit 1100. When the refrigerant container RC is mounted on the container receiving unit 1100, the refrigerant in the refrigerant container RC may be moved to the refrigerant receiving section of the container receiving unit 1100.

[0201] When the refrigerant container RC is provided as a cartridge and mounted on the container receiving unit 1100, components may be required to perforate the cartridge inlet to allow the refrigerant to exit the cartridge, and components to seal the perforated cartridge inlet to prevent the refrigerant from leaking to the outside. Therefore, the components for perforation and sealing may be installed between the container receiving unit 1100 and the refrigerant container RC.

[0202] In another example, the refrigerant container RC may be provided as a tank that is difficult to transport, and the container receiving unit 1100 may be connected to the refrigerant container RC via a pipe. The refrigerant in the refrigerant container RC may be moved through the pipe to the refrigerant receiving section of the container receiving unit 1100.

[0203] The flow control unit 1200 can control the movement of the refrigerant. For example, the flow control unit 1200 may include a valve, and the refrigerant may or may not move depending on whether the valve is open or closed. Furthermore, the degree to which the refrigerant moves may be determined depending on the ratio of the valve's opening.

[0204] Here, the valve may be a solenoid valve, but the technical concept of this disclosure is not limited thereto.

[0205] The container receiving unit 1100 and the flow control unit 1200 are fluidically connected to each other, so that the refrigerant introduced into the refrigerant containment section of the container receiving unit 1100 moves to the flow control unit 1200. For example, the refrigerant receiving section of the container receiving unit 1100 and the flow path of the flow control unit 1200 may be directly connected to each other. In another example, the refrigerant receiving section of the container receiving unit 1100 and the flow control unit 1200 may be connected to each other through a conduit.

[0206] As will be described later, the refrigerant injection device 1000 may be equipped with a precise temperature control function that precisely controls the temperature of the injection area in which the refrigerant is injected. The heat generating unit 1300 is one means of implementing the precise temperature control function and can provide heat to the refrigerant before it is injected.

[0207] To achieve the objective of precisely controlling the temperature of the injection area, the refrigerant injection device 1000 may use a heat generating unit 1300 to heat the high-pressure / low-temperature refrigerant before it is injected.

[0208] The heat generating unit 1300 may include a heat source and a heat transfer medium. The heat source is a component that generates heat and may include, for example, an element that uses a thermoelectric effect such as the Peltier effect. In this case, the amount of thermal energy generated by the heat source may vary depending on the magnitude of the power or current supplied to the heat source. The heat transfer medium may provide the heating generated by the heat source to the refrigerant. For example, the heat transfer medium may receive thermal energy from the heat source and transfer the received thermal energy to the refrigerant.

[0209] The heat transfer medium can be configured in various forms. For example, a heat source may be thermally connected to the heat transfer medium, and at least one channel for the movement of a refrigerant may be formed inside the heat transfer medium, thus providing a component that maximizes the contact area (i.e., heat transfer area) between the heat transfer medium and the refrigerant.

[0210] The flow control unit 1200 and the heat generation unit 1300 may be fluidically connected to each other, so that the refrigerant moves from the flow control unit 1200 to the heat generation unit 1300. For example, the flow path of the flow control unit 1200 and the flow path of the heat generation unit 1300 may be directly connected to each other. In another example, the flow control unit 1200 and the heat generation unit 1300 may be connected to each other through a conduit.

[0211] The refrigerant can be injected through a nozzle 1500. The nozzle 1500 has a flow path formed within it for the refrigerant to flow through. The flow path formed within the nozzle 1500 is narrower at the other end from which the refrigerant is discharged compared to the one end from which the refrigerant enters. Before the refrigerant is injected from the other end of the nozzle 1500, it is maintained at a high pressure, and the refrigerant injected from the other end of the nozzle 1500 is injected at a high speed while expanding adiabatically and is rapidly cooled. Here, the higher the pressure of the refrigerant introduced into the nozzle 1500, the lower the temperature and the higher the speed at which the refrigerant expands adiabatically. For example, when the internal pressure of the refrigerant container RC is 50 bar, the pressure of the refrigerant introduced into the nozzle 1500 may also be close to 50 bar, and the temperature of the refrigerant injected from the nozzle 1500 may be about -50°C. If a cryogenic refrigerant with the high pressure required for high-speed injection is injected directly onto the skin, it can cause cell necrosis. To prevent skin damage such as cell necrosis, thermal energy may be applied using the heat generating unit 1300 described above before the coolant is sprayed.

[0212] The nozzle 1500 is attachable to and detachable from the refrigerant injection device 1000. A nozzle coupling unit 1400 may be provided for attaching or detaching the nozzle 1500 to or from the refrigerant injection device 1000.

[0213] The composition supply device 2000 may be mounted on the nozzle 1500. For example, a portion of the composition supply device 2000 may be connected to the nozzle 1500, so that the output end of the composition guide 2100 of the composition supply device 2000 is positioned adjacent to the opening of the nozzle 1500.

[0214] On the other hand, the flow control unit 1200, the heat generation unit 1300, and the nozzle 1500 are fluidically connected to each other and can be arranged in various ways. For example, the heat generation unit 1300 may be installed between the flow control unit 1200 and the nozzle 1500, so that the refrigerant passes through the flow control unit 1200, reaches the heat generation unit 1300, passes through the heat generation unit 1300, and reaches the nozzle 1500. In another example, the flow control unit 1200 may be installed between the heat generation unit 1300 and the nozzle 1500, so that the refrigerant passes through the heat generation unit 1300, reaches the flow control unit 1200, passes through the flow control unit 1200, and reaches the nozzle 1500.

[0215] The sensor unit 1600 can measure the temperature of the injection area where the refrigerant is injected. For example, the sensor unit 1600 can measure the temperature of the skin surface to which the refrigerant is injected and provide the measurement information to the controller 1900.

[0216] On the other hand, the sensor unit 1600 can measure the temperature of some of the components of the composition supply device 2000. For example, the sensor unit 1600 can measure the temperature of the composition guide 2100 or the mixing unit 2300 and provide the measurement information to the controller 1900.

[0217] The input unit 1700 can receive user input. For example, the input unit 1700 may include at least one push-button switch that, in response to user pressure on the switch, provides a push input signal to the controller 1900, which in turn can control the opening and closing of the flow control unit 1200 based on the push input signal. In addition, the input unit 1700 may include at least one rotary switch that, in response to user operation, provides a rotary input signal to the controller 1900, which in turn can set a target temperature or target time based on the rotary input signal. Here, the target temperature refers to the temperature to be reached by adjusting the temperature of the injection area. In addition, the target time refers to the time for which the injection of the refrigerant must be maintained, or for which the temperature of the injection area must be maintained at the target temperature. In addition, the user may use the input unit 1700 to set a target penetration depth of the composition. As will be described later, the mixed injection system 100 may adjust the penetration depth by controlling the size of the frozen particles by controlling the heat applied to the refrigerant or the flow rate of the composition.

[0218] The output unit 1800 can output an interface for using the refrigerant injection device 1000 and various information to the user. For example, the output unit 1800 may include a display, which may output an interface for setting the target temperature or target time via the display, and may output information such as the real-time temperature of the injection area measured by the sensor unit 1600, or the total time the refrigerant has been injected, while the refrigerant injection device 1000 is being operated.

[0219] The controller 1900 can control the components of the refrigerant injection device 1000. For example, the controller 1900 can control the temperature of the injected refrigerant by controlling the heat generation unit 1300, control the flow of the refrigerant by controlling the flow adjustment unit 1200, and output specific information to the user through the output unit 1800.

[0220] The refrigerant injection device 1000 can be operated in the following manner.

[0221] First, the controller 1900 can set a target temperature and a target time. For example, the controller 1900 may provide an interface through the output unit 1800 to guide the user to set a target temperature and a target time, receive a setting input signal in response to user operation through the input unit 1700, and set the target temperature and a target time based on the received setting input signal.

[0222] Subsequently, the controller 1900 may output a message through the output unit 1800 instructing the user that it is ready for operation, receive a switch-on input signal in response to user operation through the input unit 1700, and enable the refrigerant to be injected based on the received switch-on input signal.

[0223] The controller 1900 can perform precise cooling of the injection area while the refrigerant is being injected. For example, while the refrigerant is being injected, the controller 1900 can acquire the real-time temperature of the injection area measured by the sensor unit 1600 and control the heat generation unit 1300 by comparing the acquired real-time temperature with a set target temperature. Specifically, when the acquired temperature is lower than the target temperature, the controller 1900 can increase the thermal energy applied to the refrigerant through the heat generation unit 1300, and when the acquired temperature is higher than the target temperature, the controller 1900 can decrease the thermal energy applied to the refrigerant through the heat generation unit 1300. Here, the controller 1900 can use proportional integral derivative (PID) control as a feedback control technique.

[0224] When precise cooling is performed by the controller 1900, the temperature in the injection area can be controlled within a predetermined error range based on the target temperature.

[0225] On the other hand, the controller 1900 uses the heat generation unit 1300 to supply heat to the refrigerant, regardless of the temperature of the injection area. For example, the controller 1900 may control the heat generation unit 1300 to provide a predetermined amount of thermal energy per unit time. In this case, temperature measurement of the injection area may not be performed.

[0226] Although not shown in Figure 9, the refrigerant injection device 1000 may further include a distance maintenance unit. When injecting the refrigerant into the injection area, it is preferable that the distance between the target area and the refrigerant injection device 1000 be kept constant. For example, it is preferable that the refrigerant and composition are injected while the nozzle 1500 of the refrigerant injection device 1000 is positioned within a recommended injection distance range relative to the target area.

[0227] In particular, when it is necessary to measure and monitor the temperature of the injection area in the refrigerant injection device 1000 (for example, when feedback control is performed using the temperature of the target area, when the temperature of the target area drops to or below the safety temperature and the device stops operating, or when the real-time temperature of the target area is output to the user), the temperature of the injection area must be measured accurately.

[0228] The distance maintenance unit may be positioned adjacent to the nozzle 1500. The distance maintenance unit may be connected to the housing of the refrigerant injection device 1000. The length of the distance maintenance unit may be designed such that the distance from the opening of the nozzle 1500 to the end of the distance maintenance unit in a direction parallel to the central axis CA of the nozzle 1500 is within the recommended injection distance range. For example, the length of the distance maintenance unit may be determined based on the injection distance to maintain the freezing rate of the composition to a predetermined value or greater.

[0229] On the other hand, the refrigerant injection device 1000 is not limited to the above embodiment, and any device or structure that performs the function of injecting refrigerant by directly or indirectly connecting to the refrigerant container RC through a pipe may be considered the refrigerant injection device 1000 described herein. For example, the refrigerant injection device 1000 may not heat the refrigerant, and therefore the heat generating unit 1300 and the sensor unit 1600 may be omitted.

[0230] Figure 10 is a diagram illustrating a composition supply device 2000 according to the first embodiment. Figure 10(a) shows the composition supply device 2000 connected to the nozzle 1500, and Figure 10(b) shows the composition and refrigerant that are mixed and sprayed into cross section A-A' while the composition supply device 2000 is connected to the nozzle 1500.

[0231] Referring to Figure 10, the composition supply device 2000 may include a composition guide 2100, a mixing unit 2300, a composition container CC, and a connecting portion 2400.

[0232] The composition guide 2100 functions to guide the movement of the composition. For example, as shown in Figure 10(b), the composition guide 2100 may fluidly connect the composition container CC and the mixing unit 2300, and the composition stored in the composition container CC may move to the mixing unit 2300 through the composition guide 2100. The composition guide 2100 may be implemented in the form of a tube. The composition guide 2100 may include an input end through which the composition is introduced and an output end through which the composition is discharged.

[0233] The mixing unit 2300 provides a mixing space MS into which the composition and refrigerant are mixed. As shown in Figure 10(b), the mixing unit 2300 has an inner surface that defines the mixing space MS. The output end of the composition guide 2100 may be located on the inner surface of the mixing unit 2300. The mixing space MS may be fluidically connected to the nozzle 1500 of the refrigerant injection device 1000, and when the refrigerant is injected from the nozzle 1500, a refrigerant injection stream RSS may be formed in the mixing space MS.

[0234] The refrigerant injection stream RSS can be divided into a main stream S1 and a substream S2. Mainstream S1 may refer to a region where the refrigerant is injected relatively strongly, and substream S2 may refer to a region where the refrigerant is injected relatively weakly. Alternatively, mainstream S1 may refer to a region where the refrigerant density is relatively high, and substream S2 may refer to a region where the refrigerant density is relatively low.

[0235] The main stream S1 and substream S2 can be divided based on the central axis CA of the nozzle 1500. For example, when the refrigerant injection stream RSS is cut perpendicular to the central axis CA of the nozzle 1500, the main stream S1 may be located within the boundary distance from the central axis CA of the nozzle 1500, and the substream S2 may be located outside the boundary distance from the central axis CA of the nozzle 1500. The boundary distance may vary depending on the distance from the end of the nozzle 1500, the internal pressure of the refrigerant container RC, and the size of the opening of the nozzle 1500. In another example, the region where the refrigerant temperature is equal to or lower than the threshold temperature in the refrigerant injection stream RSS may be the main stream S1, and the remaining region may be the substream S2. In another example, the region where the average velocity of the refrigerant is equal to or greater than the threshold velocity in the refrigerant injection stream RSS may be the main stream S1, and the remaining region may be the substream S2. In another example, the region where the density of the refrigerant is equal to or greater than the threshold density in the refrigerant injection stream RSS may be the main stream S1, and the remaining region may be the substream S2.

[0236] On the other hand, it is important that the composition is introduced into the main stream S1 of the refrigerant injection stream RSS. Compared to the substream S2, the refrigerant velocity is faster and its temperature is lower in the main stream S1. Therefore, when the composition is injected in the main stream S1 in contact with the refrigerant particles, the temperature of the composition is lower and the injection velocity of the composition is also higher compared to when the composition is injected in the main stream S1 in contact with the refrigerant particles at the injection velocity of the substream S2.

[0237] The composition container CC may store the composition therein. The composition container CC may have an inlet through which the composition is injected. The composition container CC may have a vent through which external air is introduced.

[0238] The connecting portion 2400 refers to the portion of the composition supply device 2000 that is connected to the nozzle 1500. For example, the connecting portion 2400 may include a hook connecting member, a screw connecting member, or a pressure-fit connecting member, and may be connected to and fixed to one area of ​​the nozzle 1500.

[0239] When the refrigerant injection stream RSS is formed in the mixing space MS, the refrigerant is injected adjacent to the output end of the composition guide 2100, and a negative pressure is formed at the output end of the composition guide 2100 according to Bernoulli's principle. Since the composition container CC has a vent, its internal pressure is maintained at atmospheric pressure. Therefore, the composition stored in the composition container CC moves to the output end of the composition guide 2100 where a lower pressure is formed, and as a result is introduced into the refrigerant injection stream RSS.

[0240] On the other hand, a guide plate for moving the composition to the main stream S1 of the refrigerant injection stream RSS may be installed in the mixing unit 2300. The guide plate includes a surface having a predetermined length. The first end of the guide plate may be installed adjacent to the output end of the composition guide 2100, and the second end of the guide plate may be installed adjacent to the main stream S1. Thus, the composition introduced through the composition guide 2100 can move along the guide plate and reach the main stream S1.

[0241] The components of the composition dispenser 2000 may be manufactured as a single unit. Alternatively, at least some of the components of the composition dispenser 2000 may be manufactured separately and connected to one another.

[0242] Figure 11 illustrates a composition supply device 2000 according to a second embodiment. Figure 11(a) shows the composition supply device 2000 connected to the nozzle 1500, and Figure 11(b) shows the composition and refrigerant that are mixed and sprayed into cross section B-B' while the composition supply device 2000 is connected to the nozzle 1500.

[0243] Referring to Figure 11, the composition supply device 2000 may include a composition guide 2100, a composition container CC, an actuator 2200, and a connecting portion 2400.

[0244] The composition guide 2100 is a component that receives the composition from the composition container CC and supplies the composition to the refrigerant injection stream RSS. The composition guide 2100 may include an input end through which the composition is introduced and an output end through which the composition is discharged.

[0245] Referring to Figure 11(b), a composition channel through which the composition moves is formed inside the composition guide 2100, and the output end of the composition guide 2100 may be positioned adjacent to the opening of the nozzle 1500. Specifically, the output end of the composition guide 2100 may be positioned a distance from the opening of the nozzle 1500 by a first distance in a direction parallel to the central axis CA of the nozzle 1500, and a second distance in a direction perpendicular to the central axis CA of the nozzle 1500. Here, the output end of the composition guide 2100 may be positioned to contact the main stream S1 of the refrigerant injection stream RSS formed by the nozzle 1500. For example, the first and second distances may be determined based on the boundaries of the main stream S1 and substream S2 of the refrigerant injection stream RSS. The positional relationship between the output end of the composition guide 2100 and the nozzle 1500 will be described later.

[0246] The composition container CC is a component that stores the composition therein. The composition container CC may have an inlet through which the composition is injected. The composition container CC may be fluidly connected to the actuator 2200. The composition inside the composition container CC may be pressurized by the actuator 2200 and moved to the composition guide 2100.

[0247] The actuator 2200 may be configured to supply fluid to the mixing unit 2300 at a preset flow rate. The actuator 2200 may include, for example, a piston and an electric motor, and can pressurize the fluid by moving the piston with electric power.

[0248] The connecting section 2400 is identical to the one described above, so its description is omitted.

[0249] Referring to Figure 11(b), when the refrigerant injection stream RSS is formed by the refrigerant injection device 1000, the actuator 2200 of the composition supply device 2000 may be operated to pressurize the composition in the composition container CC, thereby introducing the composition into the refrigerant injection stream RSS through the composition guide 2100. Here, the flow control unit 1200 and the actuator 2200 may be controlled by the controller 1900. For example, the flow control unit 1200 may first be operated to inject the refrigerant, and then the actuator 2200 may be operated to discharge the composition. In another example, the flow control unit 1200 and the actuator 2200 may be operated simultaneously.

[0250] As explained above, the refrigerant injection device 1000 and the composition supply device 2000 are manufactured separately and connected to each other, but the technical concept of the present disclosure is not limited thereto. For example, some components of the composition supply device 2000 may be mounted on the refrigerant injection device 1000, and some components of the refrigerant injection device 1000 may be implemented in the composition supply device 2000. Specifically, the composition supply device 2000 may include a component that performs the function of a nozzle 1500, and the composition supply device 2000 may be connected to the nozzle coupling unit 1400 of the refrigerant injection device 1000.

[0251] As described above, the refrigerant injection stream (RSS) may be formed by the refrigerant injection device 1000, and the composition may be introduced into the RSS by the composition supply device 2000. The composition introduced into the RSS is decomposed into fine particles in the RSS and can be frozen by heat exchange with a refrigerant having a relatively low temperature. Here, the size of the fine particles may be about 10 μm to about 300 μm. Alternatively, the size of the fine particles may be about 10 μm to about 100 μm.

[0252] However, as will be explained later, depending on the design and control method of the mixed injection system 100, the composition may or may not freeze, and the freezing rate may vary.

[0253] 2.4.2 Factors affecting frozen particle formation

[0254] First, factors influencing whether the composition freezes and, to what extent, may include the temperature of the refrigerant injection stream (RSS), the composition flow rate, and the composition inlet location.

[0255] The lower the temperature of the refrigerant injection stream (RSS), the easier it is for the composition to freeze. Here, the temperature of the refrigerant injection stream (RSS) may refer to the temperature measured at a point within the RSS (for example, the temperature at a point a predetermined distance from the opening of nozzle 1500). Alternatively, the temperature of the refrigerant injection stream (RSS) may refer to the average temperature of at least one region of the RSS. The lower the temperature of the refrigerant particles exchanging heat with the composition, the lower the temperature of the composition may become, thereby increasing the probability of the composition freezing. Furthermore, the lower the temperature of the refrigerant particles, the higher the freezing rate of the composition may become.

[0256] On the other hand, excessively lowering the temperature of the refrigerant injection stream (RSS) to freeze the composition can cause pain or irreversible damage to the skin. Therefore, the temperature of the refrigerant injection stream (RSS) must be controlled so as not to cause pain or damage to the skin when the composition freezes.

[0257] In addition, when the temperature of the refrigerant injection stream (RSS) drops excessively, moisture on the skin surface may freeze and form a substance that hinders penetration, such as an ice film, and the composition may not reach the skin surface but be repelled by the ice film.

[0258] The temperature of the refrigerant injection stream (RSS) can vary depending on the pressure of the refrigerant before it is injected from nozzle 1500. For example, as the pressure of the refrigerant before it is injected from nozzle 1500 increases, the temperature of the refrigerant injection stream (RSS) may decrease. This is because as the refrigerant pressure before injection increases, the difference between the pre-injection refrigerant pressure and the post-injection refrigerant pressure (atmospheric pressure) increases, and the temperature drop increases accordingly.

[0259] The refrigerant pressure before injection may be substantially the same as the internal pressure of the refrigerant container RC. In other words, as the internal pressure of the refrigerant container RC increases, the refrigerant pressure before injection may increase, and the temperature of the refrigerant injection stream RSS may decrease.

[0260] Therefore, a refrigerant container RC having a high internal pressure may be used to freeze the composition or to increase the freezing rate of the composition. Alternatively, the refrigerant container RC may be heated to increase the pressure within the refrigerant container RC.

[0261] On the other hand, in order to increase the refrigerant pressure before injection, the refrigerant injection device 1000 may further include a compressor. For example, the compressor may be installed between the nozzle 1500 and the flow control unit 1200, or between the flow control unit 1200 and the container receiving unit 1100, to increase the refrigerant pressure.

[0262] The temperature of the refrigerant injection stream (RSS) can vary depending on the degree to which the refrigerant is heated before being injected from nozzle 1500. As the amount of heated refrigerant increases, the temperature of the refrigerant injection stream (RSS) can increase. This is because the pre-injection refrigerant temperature increases, the gas ratio in the refrigerant increases, and the amount of refrigerant expanding decreases.

[0263] The amount of refrigerant that is heated can be controlled by the heat generation unit 1300 of the refrigerant injection device 1000. For example, if the heat generation unit 1300 is a thermoelectric element that generates thermal energy in response to power, the amount of thermal energy supplied from the heat generation unit 1300 to the refrigerant per unit time can be controlled by adjusting the power applied to the heat generation unit 1300.

[0264] The amount of refrigerant heated can be controlled so that the skin surface temperature is equal to or greater than the minimum temperature at which skin damage or pain occurs. For this purpose, the controller 1900 of the refrigerant injector 1000 may perform feedback control using the difference between the real-time temperature and the minimum temperature in the target area.

[0265] The temperature of the refrigerant injection stream (RSS) can be controlled by a method of controlling the refrigerant pressure before injection, a method of controlling the thermal energy applied to the refrigerant, or a combination thereof.

[0266] As the composition flow rate decreases, the composition can easily freeze. Composition flow rate refers to the amount of composition introduced into the refrigerant injection stream RSS per unit time. Alternatively, composition flow rate refers to the amount of composition supplied from the composition guide 2100 per unit time.

[0267] Since the composition introduced into the refrigerant injection stream RSS receives cooling energy from the refrigerant injection stream RSS (its temperature decreases through heat exchange), as the composition flow rate increases, the cooling energy received per unit mass of the composition decreases, and as a result, the composition may not freeze or the freezing rate may be reduced.

[0268] On the other hand, as the composition flow rate decreases, the total amount of refrigerant used to spray a specific amount of composition into a target area may increase. That is, when the composition flow rate decreases excessively, the total amount of refrigerant used to spray a specific amount of composition may increase excessively, increasing the cost and time required for freezing spraying. Alternatively, when the composition flow rate decreases excessively and a predetermined amount of refrigerant is used, the amount of composition sprayed decreases excessively, thereby reducing the amount of composition that penetrates the skin.

[0269] Therefore, the composition flow rate needs to be controlled so that the composition is frozen and the amount of composition supplied during a predetermined treatment time is equal to or greater than a predetermined level.

[0270] The composition flow rate can be adjusted using the actuator 2200. For example, when supplying the composition to the composition guide 2100, the pressure applied to the composition can be controlled to a constant level using the actuator 2200, and the composition flow rate can be controlled to a constant level depending on the magnitude of the pressure. The composition flow rate increases as the pressure applied to the composition increases, and decreases as the pressure applied to the composition decreases.

[0271] When the composition guide 2100 includes a conduit, the composition flow rate can be adjusted depending on the width of the conduit. Even when the composition is supplied from the composition container CC to the composition guide 2100 through the conduit, the composition flow rate can be adjusted depending on the width of the conduit. In other words, the composition flow rate can be determined depending on the width of the conduit designed when the conduit is manufactured. The composition flow rate increases as the width of the conduit increases, and decreases as the width of the conduit decreases.

[0272] The composition flow rate can be controlled by using the actuator 2200, by designing the width of the conduit of the composition guide 2100 or the conduit connected to the composition guide 2100, or by a combination thereof.

[0273] The closer the composition inlet is to the nozzle 1500, the better the composition can be frozen. When the composition and refrigerant are sprayed onto the skin surface using the mixing spray system 100, the composition is cooled by the refrigerant spray stream RSS from the point where it enters the refrigerant spray stream RSS until it reaches the skin surface.

[0274] In other words, the greater the distance from the point where the composition is introduced to the skin surface, the greater the time required for the composition to be cooled by the refrigerant injection stream RSS, and the greater the possibility of freezing or the degree of freezing of the composition. Alternatively, as the distance from the point where the composition is introduced to the opening of the nozzle 1500 decreases, the greater the time required for the composition to be cooled by the refrigerant injection stream RSS, and the greater the possibility of freezing or the degree of freezing of the composition.

[0275] However, the composition inlet position can be understood as the position of the output end of the composition guide 2100, and when the output end of the composition guide 2100 is positioned too close to the opening of the nozzle 1500, the refrigerant injected from the nozzle 1500 may collide with the composition guide 2100, forming turbulence. Considering the stable injection of the composition and refrigerant, and the deceleration of the refrigerant injection stream RCC due to turbulence, it is preferable that turbulence is not formed.

[0276] The output end of the composition guide 2100 may be positioned a distance from the opening of the nozzle 1500 by a first distance in a direction parallel to the central axis CA of the nozzle 1500, and a second distance in a direction perpendicular to the central axis CA of the nozzle 1500.

[0277] The first distance may be within approximately 20 mm. The first distance may be, for example, 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, or 20 mm.

[0278] The second distance may be within approximately 10 mm. The second distance may be, for example, 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, or 10 mm. As described above, the first and second distances can be reduced and the composition can be easily frozen, but when they are reduced excessively, the problem of turbulence formation may arise.

[0279] For example, the composition inlet position may be determined as a position corresponding to the edge of the main stream S1 of the refrigerant injection stream RSS formed by the nozzle 1500, at a predetermined distance from the nozzle 1500. In this case, the first and second distances may be determined based on the boundary between the main stream S1 and the substream S2 of the refrigerant injection stream RSS.

[0280] 2.4.3 Implementation of a system for freeze injection

[0281] To implement the mixed injection system 100 that enables freeze injection, the refrigerant injection stream temperature, composition flow rate, composition inlet position, or a combination thereof as described above may be considered.

[0282] Basically, the hybrid injection system 100 needs to be implemented such that the composition freezes on the skin surface. To achieve this, the temperature of the refrigerant injection stream RSS formed in the hybrid injection system 100 needs to be equal to or lower than the freezing point of the composition. In particular, the temperature of the refrigerant injection stream RSS at the location or region where the composition is introduced needs to be equal to or lower than the freezing point of the composition. For example, the freezing point of the composition can be from about -30°C to about 0°C. In this case, the temperature of the refrigerant injection stream RSS can be controlled to be equal to or lower than about -50°C or about -30°C at the location where the composition is introduced.

[0283] The hybrid injection system 100 needs to be implemented such that the freezing rate of the composition on the skin surface is equal to or greater than the target freezing rate. The target freezing rate refers to the ratio of the solid composition to the composition reaching the skin surface. Here, the target freezing rate can be calculated according to the above-mentioned freezing rate calculation method.

[0284] The target freezing rate can be determined through a freezing injection experiment. For example, as will be described later, an effective ratio range with a significant penetration effect of the composition can be calculated by conducting an experiment on the freezing injection, and the target freezing rate can be selected within the effective ratio range. For example, through the first experiment described later, a significant penetration effect is confirmed when the freezing rate is 17% or 5%, and through the second experiment described later, it is confirmed that the penetration effect increases as the freezing rate increases. As a result, the target freezing rate can be determined to be equal to or greater than 17%. Alternatively, the target freezing rate can be determined to be equal to or greater than 5%. The target freezing rate needs to be set as high as possible, but limitations described later (e.g., prevention of skin damage, prevention of ice film formation, etc.) can be further considered.

[0285] The composition supply device 2000 can be designed to have an appropriate composition flow rate (e.g., a target flow rate) in consideration of the freezing rate of the composition. Here, the target flow rate can be the composition flow rate that needs to be injected over a predetermined period. The pressure that needs to be provided by the actuator 2200 can be specified based on the determined target flow rate. Alternatively, the width of the conduit included in the composition guide 2100, or the width of the conduit connected to the composition guide 2100, can be determined based on the determined target flow rate.

[0286] The composition supply device 2000 can be designed to have an appropriate target inflow position for the composition in consideration of the freezing rate of the composition. That is, the positional relationship between the refrigerant injection device 1000 and the composition supply device 2000 can be specified to determine an appropriate target inflow position for the composition. As described above, the target inflow position can be determined as a position adjacent to the nozzle 1500 where the formation of vortices is minimized, based on the opening of the nozzle 1500. The positional relationship between the nozzle 1500 of the refrigerant injection device 1000 and the composition guide 2100 can be specified depending on the target inflow position. Specifically, the output end through which the composition is discharged from the composition guide 2100 can be designed to be located at the target inflow position based on the opening of the nozzle 1500.

[0287] The refrigerant injection device 1000 can be designed such that the refrigerant has an appropriate temperature in consideration of the freezing rate of the composition. For example, when injecting the composition and the refrigerant from the mixing injection system 100, the heat generation unit 1300 can be controlled such that the calculated freezing rate is equal to or greater than the target freezing rate. Specifically, when determining the freezing rate of the composition in the observation region OR of the refrigerant injection stream RSS while changing the heat energy per unit time generated by the heat generation unit 1300 using the controller 1900, the operating range of the heat generation unit 1300 where the freezing rate is equal to or greater than the target freezing rate can be specified.

[0288] Here, when the heat generation unit 1300 is implemented as a thermoelectric element, the operating range may refer to the power range that needs to be applied to the heat generation unit 1300. Also, here, when the heat generation unit 1300 is implemented as a thermoelectric element and the controller 1900 applies power to the thermoelectric element through feedback control using a preset target temperature and the real-time temperature of the skin surface, the operating range may refer to the range of target temperatures that need to be set.

[0289] The controller 1900 can control the heat generating unit 1300 so that it operates within a specified operating range. For example, the controller 1900 can apply power to the heat generating unit 1300 within a preset power range. The preset power range may refer to a range where the freezing rate is 5% to 100%. Alternatively, the preset power range may refer to a range where the freezing rate is 17% to 100%. Alternatively, the preset power range may refer to a range where the freezing rate is 48% to 100%. Alternatively, the preset power range may refer to a range where the freezing rate is 71% to 100%.

[0290] On the other hand, the operating range of the heat generating unit 1300 may be specified by further considering the range in which the temperature of the refrigerant injection stream RSS does not cause pain or injury to the skin surface. For example, when the composition and refrigerant are injected onto the skin surface from the mixed injection system 100, the heat generating unit 1300 may be determined such that the temperature of the skin surface is equal to or greater than the safe temperature. The safe temperature may be determined within the range of about -10°C to about 20°C. For example, the safe temperature may be -10°C, -9°C, -8°C, -7°C, -6°C, -5°C, -4°C, -3°C, -2°C, -1°C, 0°C, 1°C, 2°C, 3°C, 4°C, 5°C, 6°C, 7°C, 8°C, 9°C, 10°C, 11°C, 12°C, 13°C, 14°C, 15°C, 16°C, 17°C, 18°C, 19°C, or 20°C.

[0291] Furthermore, the operating range of the heat generating unit 1300 may be specified by further considering the range in which an ice film, which is a penetration-inhibiting substance, does not form on the skin surface by the refrigerant injection stream RSS. For example, when the composition and refrigerant are injected onto the skin surface from the mixed injection system 100, the operating range of the heat generating unit 1300 may be determined such that the skin surface temperature is equal to or greater than the ice film formation temperature. The ice film formation temperature is 0°C, since an ice film can form when the skin surface is equal to or lower than 0°C.

[0292] On the other hand, the controller 1900 may not operate the heat generating unit 1300, or the heat generating unit 1300 may be omitted from the mixed injection system 100. Specifically, a composition having room temperature may be introduced into the refrigerant injection stream RSS, causing the temperature of the refrigerant injection stream RSS to increase. This is because, by introducing the composition, when the temperature of the refrigerant injection stream RSS rises above the safe temperature and / or ice film formation temperature, the potential for freezing or the freezing rate of the composition may increase by not heating the refrigerant before injection.

[0293] The refrigerant pressure can be controlled to control the temperature of the refrigerant injection stream (RSS).

[0294] First, the internal pressure of the refrigerant container RC used in the mixed injection system 100 can be appropriately selected considering the freezing rate of the composition. For example, the internal pressure of the refrigerant container RC can be determined within the range of 10 bar to 1,000 bar. Preferably, the internal pressure of the refrigerant container RC is determined within the range of 30 bar to 200 bar.

[0295] The internal pressure of the refrigerant container RC may be determined considering the target freezing rate and the safe temperature. For example, the internal pressure of the refrigerant container RC may be determined between the minimum pressure value at which the freezing rate of the composition reaches the target freezing rate and the maximum pressure value at which the skin surface temperature reaches a safe temperature.

[0296] On the other hand, the refrigerant pressure can be controlled by a separate compressor and / or a container heater that heats the refrigerant container RC, as described above. The compressor or container heater can control the refrigerant pressure before injection to a pressure range determined based on the target freezing rate and safety temperature.

[0297] In the above, it was explained that in the implementation of the mixed injection system 100 for freeze injection, the composition flow rate, composition inlet position, and refrigerant injection stream temperature are considered in sequence. However, the technical ideas of this disclosure are not limited thereto, and the mixed injection system 100 may be designed so that these factors are considered in a different order.

[0298] As a result, the implemented mixed injection system 100 includes a refrigerant container RC that stores refrigerant at a pressure of at least 30 bar to 200 bar, a refrigerant receiving section that receives refrigerant from the refrigerant container RC, a nozzle 1500 having an opening of a preset size, a composition guide 2100 installed adjacent to the nozzle 1500 (the output end of the composition guide 2100 is located within a preset distance from the opening of the nozzle 1500), a flow adjustment unit 1200, and a controller 1900. Here, the freezing rate of the composition in an observation area OR located at an observation distance OD away from the opening of the nozzle 1500 and having an observation width OW is equal to or greater than the target freezing rate. The mixed injection system 100 may further include a distance maintenance unit, which may have a length within a recommended injection distance range to ensure that the freezing rate of the composition is equal to or greater than the target freezing rate.

[0299] Above, a mixed spray system 100 implemented to enable freeze spraying was described. A mixed spray system 100 implemented so that at least a portion of the composition is frozen and reaches the skin surface may also be called a freeze spraying system.

[0300] 2.4.4 Spraying of the composition after freezing

[0301] The hybrid injection system 100 described above injects a composition together with a refrigerant, and as a result, the composition is frozen by the refrigerant during injection. However, a system for performing cryogenic injection cannot be implemented simply by injecting a mixture of the composition and the refrigerant, and any system can be used for cryogenic injection as long as it enables the frozen composition to reach the skin surface. For example, a system that pre-freezes the composition and injects the frozen composition can be used. Specifically, a system that pre-freezes the composition to generate frozen particles and then injects the frozen particles onto the skin surface using a transmission medium such as compressed air can be used.

[0302] 2.5 Cryogenic Injection Method

[0303] Hereinafter, a cryogenic injection method using the hybrid injection system 100 will be described with reference to FIG. 12.

[0304] FIG. 12 is a flowchart illustrating a cryogenic injection method according to an embodiment.

[0305] Referring to FIG. 12, the cryogenic injection method includes preparing the hybrid injection system 100 (S1100), positioning the hybrid injection system 100 based on the target area (S1300), and injecting both the composition and the refrigerant into the target area using the hybrid injection system 100 (S1500).

[0306] Hereinafter, each step will be described in detail.

[0307] First, a user (or operator) may prepare the hybrid injection system 100 (S1100). The hybrid injection system 100 includes at least a nozzle 1500 for forming a refrigerant injection stream RSS and a composition guide 2100 installed adjacent to the nozzle 1500. The hybrid injection system 100 may include other components described above in addition to the nozzle 1500 and the composition guide 2100.

[0308] The user may position the hybrid injection system 100 based on the target area (S1300).

[0309] For example, the user can position the nozzle 1500 of the mixing injection system 100 at a predetermined distance from the target area.

[0310] Here, the predetermined distance may refer to the shortest distance between the opening of the nozzle 1500 and the target area. The predetermined distance may be substantially the same as the recommended spray distance described above. When the recommended spray distance is presented as a range, the predetermined distance may fall within the recommended spray distance range.

[0311] Furthermore, the central axis CA of the nozzle 1500 may have a predetermined angle with respect to the target area. For example, the angle formed between the central axis CA of the nozzle 1500 and the plane containing the target area or a virtual plane in contact with the target area may have a value of approximately 45° to approximately 90°.

[0312] The user can use the mixed injection system 100 to inject both the composition and the refrigerant into a target area (S1500). For example, when the user operates an input unit 1700 provided in the mixed injection system 100, the flow control unit 1200 may be opened, the actuator 2200 may pressurize the composition, and both the refrigerant and the composition may be injected into the target area. If the mixed injection system 100 does not include the actuator 2200, when the user operates the input unit 1700 (for example, when the user presses the injection start button), the flow control unit 1200 may be opened to form a refrigerant injection stream RSS, and the composition may be introduced into the refrigerant injection stream RSS due to negative pressure and then injected.

[0313] When the mixing injection system 100 is operated, the composition stored in a liquid state is introduced into the refrigerant injection stream RSS. Due to the refrigerant injection stream RSS, the liquid composition is broken down into fine particles, and simultaneously, as its temperature decreases, it transitions to a solid state in the form of frozen fine particles. The solid composition is accelerated in the acceleration section of the refrigerant injection stream RSS and reaches the target region. In addition, when the mixing injection system 100 is viewed from the side at the time of operation, an observation region OR with an observation width OW may be specified, which is located at an observation distance OD corresponding to a predetermined distance from the opening of the nozzle 1500, and the freezing rate in the observation region OR may be 5%.

[0314] 2.6 Confirmation of the penetration effect of freeze spraying

[0315] The skin penetration effect of freeze spray will be explained through experiments on freeze spray.

[0316] 2.6.1 Experiments on Freeze Injection

[0317] The applicant conducted various experiments on freeze-injection, including experiments on the penetration effect dependent on freezing and experiments on the penetration effect dependent on the freezing rate.

[0318] First, the first experiment, which confirms the freezing-dependent osmotic effect, is described.

[0319] The objective of the first experiment was to confirm that the penetration effect varied depending on whether the composition was frozen or not.

[0320] In the first experiment, the penetration effect was compared when the composition was sprayed onto the skin surface in an unfrozen state (test group 1), when the composition was sprayed onto the skin surface in a partially frozen state (test groups 2 and 4), and when the composition was sprayed onto the skin surface in a nearly frozen state (test group 3).

[0321] Human skin tissue was used as the target to which the composition was sprayed. Specifically, facial skin tissue discarded after surgery was used.

[0322] In the control group, human-derived skin tissue was cut to a predetermined size (2 cm x 2 cm), and the composition was applied to it. To confirm the penetration effect, the composition contained acetyl hexapeptide-8-FITC combined with a fluorescent substance (fluorescein isothiocyanate, FITC).

[0323] Next, 24 hours later, fluorescence images were taken of cross-sections of human-derived skin tissue, and the intensity and penetration depth of the fluorescent substance located beneath the epidermis were measured.

[0324] In test group 1, human skin tissue was cut to a predetermined size, and the composition was sprayed onto it without freezing. The composition contained an antifreeze (PG) to prevent freezing by the refrigerant, and acetyl hexapeptide-8-FITC combined with a fluorescent substance (FITC) to confirm the penetration effect.

[0325] The above-described mixing injection system 100 was used to inject the composition. Specifically, the refrigerant injection device 1000 described above and the composition supply device 2000 according to the second embodiment were used. In the mixing injection system 100 used, the freezing rate was calculated to be 0%.

[0326] Next, 24 hours later, fluorescence images were taken of cross-sections of human-derived skin tissue, and the intensity and penetration depth of the fluorescent substance located beneath the epidermis were measured.

[0327] In test group 2, human-derived skin tissue was cut to a predetermined size, and only a portion of the composition was frozen and sprayed onto it. The composition included acetyl hexapeptide-8-FITC combined with a fluorescent substance (FITC) to confirm its penetration effect.

[0328] The above-described mixing injection system 100 was used to inject the composition. Specifically, the refrigerant injection device 1000 described above and the composition supply device 2000 according to the second embodiment were used. For the mixing injection system 100 used, the freezing rate was calculated to be 17% (within a 5% measurement error, approximately 12% to approximately 22%).

[0329] Next, 24 hours later, fluorescence images were taken of cross-sections of human-derived skin tissue, and the intensity and penetration depth of the fluorescent substance located beneath the epidermis were measured.

[0330] In test group 3, human-derived skin tissue was cut to a predetermined size, the majority of the composition was frozen, and then sprayed onto it. The composition included acetyl hexapeptide-8-FITC combined with a fluorescent substance (FITC) to confirm its penetration effect.

[0331] The above-described mixing injection system 100 was used to inject the composition. Specifically, the refrigerant injection device 1000 described above and the composition supply device 2000 according to the second embodiment were used. For the mixing injection system 100 used, the freezing rate was calculated to be 100% (within a 1% measurement error, approximately 99% to approximately 100%).

[0332] Next, 24 hours later, fluorescence images were taken of cross-sections of human-derived skin tissue, and the intensity and penetration depth of the fluorescent substance located beneath the epidermis were measured.

[0333] In test group 4, human-derived skin tissue was cut to a predetermined size, and only a portion of the composition was frozen and sprayed onto it. The composition included acetyl hexapeptide-8-FITC combined with a fluorescent substance (FITC) to confirm its penetration effect.

[0334] The above-described mixed injection system 100 was used to inject the composition. Specifically, the refrigerant injection device 1000 and composition supply device 2000 according to the first embodiment were used. For the mixed injection system 100 used, the freezing rate was calculated to be 5% (within a 1% measurement error, approximately 4% to 6%).

[0335] Next, 24 hours later, fluorescence images were taken of cross-sections of human-derived skin tissue, and the intensity and penetration depth of the fluorescent substance located beneath the epidermis were measured.

[0336] The applicant conducted a second experiment and confirmed the penetration effect, which depends on the freezing rate.

[0337] The objective of the second experiment was to confirm the permeation effect, which fluctuates depending on the freezing rate.

[0338] In the second experiment, the composition was sprayed onto the skin surface in a frozen state, and the penetration effect was compared among the following conditions: when the composition's freezing rate was 5% (within a 1% measurement error, approximately 4% to 6%) (Test Group 1), when the composition's freezing rate was 17% (within a 5% measurement error, approximately 12% to 22%) (Test Group 2), when the composition's freezing rate was 48% (within a 3% measurement error, approximately 45% to 51%) (Test Group 3), when the composition's freezing rate was 71% (within a 3% measurement error, approximately 68% to 74%) (Test Group 4), and when the composition's freezing rate was 100% (within a 1% measurement error, approximately 99% to 100%) (Test Group 5).

[0339] The mixed injection system 100 according to the second embodiment was used to inject the composition.

[0340] As a method for adjusting the freezing rate, a method was adopted to adjust the thermal energy applied to the refrigerant before it is injected from the heat generating unit 300 of the mixed injection system 100.

[0341] More specifically, the heat generating unit 1300 included a thermoelectric element, and the power applied to the thermoelectric element was regulated. As the thermal energy applied before the refrigerant was injected through the nozzle 1500 changed, the temperature of the refrigerant injection stream RSS formed at the nozzle 1500 changed, and the freezing rate of the composition changed accordingly.

[0342] Here, the applied power was adjusted using pulse width modulation (PWM), and the heating power applied using the PWM method was divided into levels from 0 to 999. In test groups 1 to 5, the freezing rate was adjusted by varying the heating power applied to the thermoelectric element.

[0343] In the second experiment, a hydrogel was used as a target for spraying the composition and refrigerant, and the penetration effect was compared by the number of holes formed in the hydrogel. The number of holes formed in the hydrogel was determined visually, and it was determined that the greater the number of holes formed after the composition and refrigerant were sprayed onto the hydrogel for a predetermined period, the greater the penetration effect.

[0344] 2.6.2 Experimental Results and Analysis

[0345] The results of the first and second experiments will be explained below with reference to Figures 13 to 16.

[0346] Figures 13 and 14 illustrate the results of the first experiment to confirm the permeation effect dependent on freezing and the permeation effect dependent on the freezing rate.

[0347] According to the results of the first experiment, the penetration effect when the composition was sprayed in a frozen state (test groups 2 and 4) was significantly higher than the penetration effect when the composition was sprayed in an unfrozen state (test group 1).

[0348] Referring to Figure 13, the fluorescence intensity was 192.04 in the control group and 637.65 in test group 1, while the fluorescence intensity was 2136.44 in test group 2 and 1399.54 in test group 4. Compared to test group 1, the penetration effect improved by approximately 3.35 times in test group 2 and by approximately 2.19 times in test group 4.

[0349] Furthermore, when observing the fluorescence images of cross-sections of skin tissue in each case, as shown in Figure 14, it was confirmed that the amount of permeated composition increased significantly in test groups 2 and 4 compared to test group 1.

[0350] On the other hand, in test group 3, the fluorescence intensity was measured at 429.05, which was lower than that of test group 1. This is because, as explained above, the lower temperature of the sprayed refrigerant caused an ice film to form on the surface of the human-derived skin tissue, resulting in a large amount of frozen particles not reaching the skin tissue surface. It is expected that the ice film will not form in areas where body heat is present, such as human skin, and therefore, the penetration effect is expected to be high when the conditions of test group 3 are applied to human skin.

[0351] Figure 15 illustrates the results of the second experiment to confirm the penetration effect dependent on the freezing rate. Figure 16 illustrates the penetration effects of test group 1 and test group 5 in the second experiment.

[0352] The results of the second experiment confirmed that the penetration effect improved as the freezing rate increased.

[0353] Referring to Figure 15, when the freezing rate was 5%, there were 2 holes; when the freezing rate was 17%, there were 5 holes; when the freezing rate was 48%, there were 10 holes; when the freezing rate was 71%, there were 15 holes; and when the freezing rate was 100%, there were 18 holes. Therefore, it was confirmed that the number of holes increased as the freezing rate increased. As a result, it can be understood that the penetration effect improves as the freezing rate increases.

[0354] The penetration effect can be confirmed with the naked eye. As shown in Figure 16, the number of pores formed in the hydrogel in test group 5 increased significantly compared to test group 1.

[0355] Based on the first and second experiments, an effective ratio range for freeze spraying can be determined. According to the first experiment, the penetration effect of the composition was significant when the freezing rate of the composition was 5% and 17%. In addition, according to the second experiment, when the freezing rate of the composition was 17%, the penetration effect improved compared to when the freezing rate was 5%; when the freezing rate of the composition was 48%, the penetration effect improved compared to when the freezing rate was 17%; when the freezing rate of the composition was 71%, the penetration effect improved compared to when the freezing rate was 48%; and when the freezing rate of the composition was 100%, the penetration effect improved compared to when the freezing rate was 71%.

[0356] Therefore, the effective ratio range can be 5% to 100%. Alternatively, the effective ratio range can be 5% to 17%. Alternatively, the effective ratio range can be 5% to 48%. Alternatively, the effective ratio range can be 5% to 71%. Alternatively, the effective ratio range can be 17% to 48%. Alternatively, the effective ratio range can be 17% to 71%. Alternatively, the effective ratio range can be 17% to 100%. Alternatively, the effective ratio range can be 48% to 71%. Alternatively, the effective ratio range can be 48% to 100%. Alternatively, the effective ratio range can be 71% to 100%.

[0357] Considering the measurement error range, the effective ratio range could be 2% to 100%. Alternatively, the effective ratio range could be 2% to 22%. Alternatively, the effective ratio range could be 2% to 51%. Alternatively, the effective ratio range could be 2% to 74%. Alternatively, the effective ratio range could be 12% to 51%. Alternatively, the effective ratio range could be 12% to 74%. Alternatively, the effective ratio range could be 12% to 100%. Alternatively, the effective ratio range could be 45% to 74%. Alternatively, the effective ratio range could be 45% to 100%. Alternatively, the effective ratio range could be 68% to 100%.

[0358] The mixing and spraying system 100 may be designed such that the freezing rate of the sprayed composition is within an effective ratio range.

[0359] 3. Control of Freeze Injection Characteristics

[0360] The significance of freeze-injection, the mixed injection system 100 for performing the freeze-injection method, and the confirmation of the penetration effect through experiments related to freeze-injection were explained above.

[0361] In freeze-injection, the frozen particles of the composition may have the following characteristics: particle size and injection velocity. These characteristics can be important control factors in commercializing the mixed injection system 100 that performs freeze-injection.

[0362] For compositions having specific viscosity and surface tension, the size of the frozen particles of the composition can be controlled by the temperature of the refrigerant injection stream (RSS), the flow rate of the RSS, and the flow rate of the composition. In addition, the size of the frozen particles can be controlled by the shape of the output end of the composition guide 2100, where the composition is located immediately before it is introduced into the refrigerant injection stream (RSS). For example, the output end of the composition guide 2100 may have a blunt or pointed shape, and the size of the frozen particles of the composition may be larger in the blunt shape than in the pointed shape.

[0363] 3.1 Control of frozen particle size in freeze-injection

[0364] The frozen particles formed by freezing a liquid composition have a particle size. The smaller the size of the frozen particles of the composition, the greater the ratio of the mass of the refrigerant in the refrigerant injection stream RSS to the mass of the composition, which has a substantially zero initial velocity immediately after the composition is introduced into the refrigerant injection stream RSS. This means that, according to the law of conservation of momentum, the smaller the size of the frozen particles of the composition, the greater the velocity of the frozen particles of the composition. However, when the size of the frozen particles of the composition is excessively reduced, the increase in surface area relative to momentum can increase air resistance. As a result, the deceleration of the injection velocity may increase as the solid composition reaches the skin surface.

[0365] Figure 17 illustrates the relationship between particle size and injection velocity according to an embodiment. The frozen particle size indicated at each point in the graph in Figure 17 refers to the average particle size of at least a portion of the frozen particles in the composition. In obtaining the graph illustrated in Figure 17, a mixed injection system 100 according to a second embodiment was used, and PWM control was used as a method to control the frozen particle size of the composition. Specifically, the frozen particle size of the composition decreases as the level of heating power applied through the PWM method increases.

[0366] Referring to Figure 17, it can be seen that the velocity of the frozen particles of the composition increases as the particle size of the composition decreases, but when the particle size of the composition decreases to a predetermined level or smaller, the velocity of the frozen particles of the composition decreases.

[0367] Therefore, the size of the frozen particles of the composition can be set based on the point at which the velocity of the frozen particles of the composition is maximum. For example, the mixing and spraying system 100 may be designed such that the average size of the frozen particles of the composition is equal to or less than about 60 μm, or close to about 20 μm. In another example, when considering the direction of increasing the freezing rate of the composition, the mixing and spraying system 100 may be designed such that the average size of the frozen particles of the composition is equal to or less than about 150 μm, or close to about 70 μm. In yet another example, the mixing and spraying system 100 may be designed such that the average size of the frozen particles of the composition is within the range of about 20 μm to about 60 μm, about 20 μm to about 100 μm, about 10 μm to 60 μm, or about 10 μm to 300 μm.

[0368] In the above, the average size of frozen particles refers to the average size of composition particles frozen in the refrigerant injection stream RSS. However, the above method for calculating the average size of frozen particles of the composition in the observation area OA may be used as a method for calculating the average size of frozen particles of the composition.

[0369] Here, the above method for controlling the temperature of the refrigerant injection stream RSS can be used as a method for controlling the size of frozen particles. For example, the size of frozen particles in the composition can be controlled by controlling the degree to which the composition is heated by the heat generating unit 1300 before the refrigerant is injected.

[0370] On the other hand, the particle size of the frozen composition (or solid composition) increases excessively, and when the frozen particles are sprayed onto the skin surface, they can irritate pain receptors and cause pain. Specifically, pain can occur when the size of the frozen particles is excessively larger than the size of skin cells (approximately 30 μm) or the size of pores on the skin surface (approximately 20 μm to approximately 50 μm). Therefore, the mixed spraying system 100 can be designed so that the size of the frozen particles is smaller than approximately 20 μm to approximately 50 μm.

[0371] The size of the frozen particles in the composition can be controlled to control the skin penetration depth of the composition.

[0372] After penetrating the epidermis, the frozen particles melt due to body heat. Since the melting time varies depending on the size of the frozen particles, the location where the composition melts within the skin varies. By controlling the size of the frozen particles, the location where the composition melts can be controlled, and the depth to which the composition penetrates can be controlled accordingly.

[0373] For example, under the same velocity conditions, the penetration depth may increase as the size of the frozen particles increases, and the penetration depth may decrease as the size of the frozen particles decreases. Therefore, after determining the target penetration depth and specifying the frozen particle size range corresponding to the determined penetration depth, at least one of the following can be selectively determined based on the corresponding frozen particle size range: the level of heating power applied to the heat generating unit 1300, the temperature of the refrigerant container RC, the shape of the output end of the composition guide 2100, the adhesive strength between the composition guide 2100 and the composition, and the flow rate of the composition.

[0374] In addition, for compositions that are not suitable for penetration into the dermis of the skin, such as compositions not classified as pharmaceuticals or drugs, the size of the frozen particles of the composition may be reduced to limit the depth of penetration into the stratum corneum. For example, the mixing and spraying system 100 may be designed / controlled so that the size of the frozen particles of the composition is about 10 μm to about 50 μm.

[0375] 3.2 Control of injection speed

[0376] The penetration effect can be improved as the velocity of the frozen particles reaches the skin surface of the composition increases.

[0377] One way to increase the velocity of the frozen particles in the composition is to reduce the size of the frozen particles. For example, the amount of refrigerant heated before injection can be increased to reduce the size of the frozen particles. Alternatively, the shape of the end of the composition guide 2100 can be manufactured to be sharper (pointed).

[0378] One method for increasing the velocity of frozen particles in a composition is to increase the injection velocity of refrigerant particles that transfer kinetic energy to the composition. For example, the injection velocity of refrigerant particles can be increased by increasing the internal pressure of the refrigerant container RC in which the refrigerant is stored.

[0379] To increase the velocity of the frozen particles of the composition, the length of the acceleration section can be ensured to be equal to or greater than a predetermined level. In other words, the refrigerant and composition can be sprayed while the skin surface and the nozzle 1500 are separated from each other by a minimum acceleration distance equal to or greater than a minimum acceleration distance. Here, the minimum acceleration distance can be selected within the range of about 3 mm to about 5 mm, or about 1 mm to about 10 mm.

[0380] The mixed injection system 100 may be designed such that the velocity of the frozen particles of the composition is equal to or greater than 50 m / s. Alternatively, the mixed injection system 100 may be designed such that the velocity of the frozen particles of the composition is equal to or greater than 60 m / s, 70 m / s, 80 m / s, 90 m / s, 100 m / s, 110 m / s, or 120 m / s. Here, the velocity of the frozen particles of the composition may refer to the average moving velocity of the composition particles moving in the refrigerant injection stream RSS. For example, the velocity of the frozen particles of the composition was obtained by tracking each frozen particle in an image captured by a high-speed camera, measuring its moving velocity, and calculating the average value. Here, the velocity of the frozen particles may be calculated as the average velocity of at least a portion of the particles in the refrigerant injection stream RSS. Alternatively, the velocity of the frozen particles may be calculated as the average velocity of the particles in the observation region OR.

[0381] On the other hand, increasing the injection velocity of the composition can prevent the composition from slowing down due to air resistance before reaching the skin surface. For example, forming a sheath jet around the refrigerant injection stream RSS can prevent the composition particles from encountering air. To form a sheath jet, the mixing injection system 100 may further include a sheath nozzle. The sheath nozzle can inject refrigerant or compressed air so as to surround the refrigerant injection stream RSS. The sheath nozzle may be positioned around the nozzle 1500 and have a ring-shaped injection port. Alternatively, the sheath nozzle may consist of a plurality of nozzles arranged around the nozzle 1500. When the temperature of the sheath jet is equal to or lower than a predetermined level (e.g., the freezing point of the composition), a decrease in the temperature of the freezing particles of the composition can be prevented.

[0382] 4. Temperature control for the target area

[0383] In a method of spraying both a refrigerant and a composition together, the temperature or pressure of the refrigerant, the resulting temperature of the skin surface, and other factors can significantly affect the ability of the composition to penetrate the skin. For example, as described above, the temperature or pressure of the refrigerant can contribute to freezing the composition and causing it to collide with the skin in a solid state.

[0384] On the other hand, regardless of whether the composition is frozen or not, the temperature of the skin surface can affect the composition's penetration ability. For example, when the skin surface temperature drops, the stratum corneum of the epidermis hardens, so the impact time when the composition hits it may be shortened, the impact force of the composition may increase accordingly, and the composition may penetrate more easily. On the other hand, as explained above, when the skin surface temperature drops excessively, an ice film may form on the skin surface, or an ice layer may form inside the skin, making it difficult for the composition to penetrate.

[0385] Therefore, the applicant conducted experiments to determine how the penetration effect of the composition varies depending on the temperature of the skin surface.

[0386] 4.1 Methods for controlling skin surface temperature

[0387] The temperature of the skin surface onto which the refrigerant and composition are sprayed can be controlled by the mixed spraying system 100. For example, when the refrigerant and composition are sprayed onto the skin surface by the mixed spraying system 100, the controller 1900 may obtain the real-time temperature of the skin surface measured in real time from the sensor unit 1600, obtain the power to be applied to the heat generating unit 1300 using a PID control method that uses the difference between a preset target temperature and the real-time temperature as the input value and the power applied to the heat generating unit 1300 as the output value, and apply the obtained power to the heat generating unit 1300 to heat the refrigerant before spraying by maintaining the skin surface temperature at the target temperature.

[0388] The skin surface temperature can be maintained at, for example, -10°C, -9°C, -8°C, -7°C, -6°C, -5°C, -4°C, -3°C, -2°C, -1°C, 0°C, 1°C, 2°C, 3°C, 4°C, 5°C, 6°C, 7°C, 8°C, 9°C, 10°C, 11°C, 12°C, 13°C, 14°C, 15°C, 16°C, 17°C, 18°C, 19°C, 20°C, 21°C, 22°C, 23°C, 24°C, or 25°C. Here, maintaining the skin surface temperature at a specific temperature means that the temperature measured on the skin surface remains within an error range (e.g., -1°C to +1°C) at a specific temperature over a predetermined period of time.

[0389] 4.2 Experiment to determine the degree of penetration depending on the skin surface temperature

[0390] In the following sections, an experiment observing the penetration ability of a composition depending on the skin surface temperature is described with reference to Figure 18, and the appropriate skin surface temperature is described with reference to the experimental data.

[0391] The experimental process is as follows:

[0392] Rabbits were used as experimental animals. After general anesthesia, the skin on the rabbits' backs was trimmed and divided into 10 areas (3 cm x 3 cm). The composition and refrigerant were sprayed using the mixing spray system 100 according to the first embodiment.

[0393] As the composition, FITC, i.e., FITC dextran (3kDa~5kDa) in which a fluorescently labeled substance is attached to dextran, was used.

[0394] Subsequently, tissue samples were collected, stained with DAPI, and the fluorescence intensity in the tissue samples was measured using a fluorescence microscope.

[0395] The subjects of the experiment included a non-treated group and experimental groups 1 to 3. For the non-treated group, FITC dextran was applied to the surface of the rabbit skin. For experimental group 1, FITC dextran was sprayed onto the surface of the rabbit skin while maintaining its temperature at -3°C. For experimental group 2, FITC dextran was sprayed onto the surface of the rabbit skin while maintaining its temperature at 0°C. For experimental group 3, FITC dextran was sprayed onto the surface of the rabbit skin while maintaining its temperature at 3°C.

[0396] Figure 18 illustrates the results of an experiment to confirm the penetration effect dependent on skin surface temperature. Figure 18(a) shows the fluorescence intensity for each experimental group, and Figure 18(b) shows the penetration capacity for each experimental group.

[0397] Referring to Figure 18, penetration capacity was higher when the refrigerant and composition were mixed and sprayed compared to when the composition was applied. In addition, during the process of spraying the refrigerant and composition, penetration capacity was highest when the skin surface temperature was maintained at 3°C, and higher when the temperature was maintained at -3°C compared to when the temperature was maintained at 0°C.

[0398] As a result, it can be seen that when the refrigerant and composition are sprayed while maintaining the skin surface temperature at approximately 3°C, the penetration ability is greatly improved.

[0399] As can be seen from the above experiment, the penetration effect of the composition improved when the skin surface temperature was maintained at a specific temperature. Therefore, as will be explained later, it is necessary to determine the penetration capacity of the composition while controlling the target temperature of the skin surface, and to find a target temperature at which the penetration capacity of the composition exceeds a predetermined level.

[0400] 4.3 Method for determining the target temperature

[0401] Next, we will describe a prophetic example for determining the target temperature at which the skin surface temperature needs to be maintained.

[0402] The third experiment will be conducted as follows.

[0403] A mixed injection system 100 is prepared. Here, as described above, the mixed injection system 100 includes a refrigerant injection device 1000 that generates a refrigerant injection stream RSS, and a composition supply device 2000 connected thereto that enables the composition to be introduced into the refrigerant injection stream RSS. The internal pressure of the refrigerant container RC in which the refrigerant is stored is 50 bar, and carbon dioxide is used as the refrigerant.

[0404] The refrigerant injection device 1000 of the mixed injection system 100 includes a thermoelectric element for applying heat to the refrigerant and employs a PID control method that provides power to the thermoelectric element based on real-time temperature obtained by measuring the temperature of a target area.

[0405] Rabbits are used as experimental animals. After general anesthesia, the skin on the rabbit's back is trimmed and divided into 10 areas (3 cm x 3 cm). The composition and refrigerant are sprayed using a mixed spray system 100. Here, the target temperature of the rabbit's skin surface is set to 0°C.

[0406] As the composition, FITC, i.e., FITC dextran (3kDa~5kDa) in which a fluorescently labeled substance is attached to dextran, is used.

[0407] After the composition and refrigerant are sprayed, tissue samples are collected, stained with DAPI, and the fluorescence intensity in the tissue samples is measured using a fluorescence microscope.

[0408] The target temperatures for the skin surface were changed to -10°C, -9°C, -8°C, -7°C, -6°C, -5°C, -4°C, -3°C, -2°C, -1°C, 0°C, 1°C, 2°C, 3°C, 4°C, 5°C, 6°C, 7°C, 8°C, 9°C, 10°C, 11°C, 12°C, 13°C, 14°C, 15°C, 16°C, 17°C, 18°C, 19°C, 20°C, 21°C, 22°C, 23°C, 24°C, and 25°C, and the fluorescence intensity (penetration) in the tissue sample was measured at each target temperature.

[0409] The threshold temperature range for when the fluorescence intensity is equal to or greater than a predetermined level can be determined.

[0410] In the future, when the mixed injection system 100 is implemented, the target temperature can be set within a threshold temperature range.

[0411] The fourth experiment will be conducted as follows.

[0412] A mixed injection system 100 is prepared. Here, as described above, the mixed injection system 100 includes a refrigerant injection device 1000 that generates a refrigerant injection stream RSS, and a composition supply device 2000 connected thereto that enables the composition to be introduced into the refrigerant injection stream RSS. The internal pressure of the refrigerant container RC in which the refrigerant is stored is 50 bar, and carbon dioxide is used as the refrigerant.

[0413] The refrigerant injection device 1000 of the mixed injection system 100 includes a thermoelectric element for applying heat to the refrigerant. The refrigerant injection device 1000 is controlled by applying a constant voltage (e.g., 1V) to the thermoelectric element during the process of injecting the refrigerant.

[0414] Rabbits are used as experimental animals. After general anesthesia, the skin on the rabbit's back is trimmed and divided into 10 areas (3 cm x 3 cm). The composition and refrigerant are sprayed using a mixed spray system 100.

[0415] As the composition, FITC, i.e., FITC dextran (3kDa~5kDa) in which a fluorescently labeled substance is attached to dextran, is used.

[0416] After the composition and refrigerant are sprayed, tissue samples are collected, stained with DAPI, and the fluorescence intensity in the tissue samples is measured using a fluorescence microscope.

[0417] The voltage applied to the thermoelectric element is changed from 0V to 5V in increments of 0.1V, and the fluorescence intensity is measured at each applied voltage.

[0418] The threshold voltage range when the fluorescence intensity is equal to or greater than a predetermined level can be determined.

[0419] In the future, when the mixed injection system 100 is implemented, the voltage applied to the thermoelectric element will be set within the threshold voltage range.

[0420] The features, structures, effects, etc., described in the embodiments are included in at least one embodiment of this disclosure, and are not necessarily limited to one embodiment. Furthermore, the features, structures, effects, etc., provided in each embodiment can be combined or modified in other embodiments by those skilled in the art to which the embodiment belongs. Accordingly, the content relating to combinations and modifications should be construed as being within the scope of this disclosure.

[0421] The embodiments described herein are provided for illustrative purposes only, and those skilled in the art will understand that various modifications, additions, and substitutions are possible without departing from the scope and spirit of the disclosure. In other words, each element specifically shown in the embodiments can be implemented in modified forms. Accordingly, matters relating to combinations and modifications should be construed as being within the scope of the disclosure, as disclosed in the appended claims.

Claims

1. A method for freezing and spraying a composition: The step of preparing a mixed injection system configured to inject a refrigerant and the composition, wherein the mixed injection system includes a nozzle configured to inject the refrigerant and a composition guide arranged adjacent to the nozzle; In the step of positioning the mixing injection system at a certain distance from the target area, the opening of the nozzle of the mixing injection system is the outlet from which the refrigerant is injected, and the opening is positioned toward the target area; By using the mixed injection system, the composition is injected together with the refrigerant into the target area. In this step, the nozzle forms a refrigerant injection stream, and the composition guide guides the liquid composition so that it is introduced into the refrigerant injection stream. A portion of the liquid composition is frozen and reaches the target area as a solid. Here, at a time point in time when the refrigerant and the composition are injected through the mixed injection system, the freezing rate, which represents the ratio of the solid state of the composition to the liquid state of the composition in the observation area, is greater than or equal to 5%. Here, the observation area is defined as an area of ​​arbitrary width in the side view of the mixing injection system, located at an observation distance from the opening of the nozzle. Here, the observation distance corresponds to the distance between the opening of the nozzle and the target area. A method for providing this.

2. A method for freezing and spraying a composition according to claim 1, wherein the observation area is defined in the side view of the mixing spray system by a first line perpendicular to the central axis of the nozzle, which is located a distance from the opening of the nozzle by the observation distance, and a second line parallel to the first line, which is located a distance of the arbitrary width from the first line.

3. A method for freezing and spraying the composition according to claim 1, wherein the observation distance is within the recommended spray distance range determined for the mixing spray system.

4. The method for freezing and spraying a composition according to claim 1, wherein the freezing rate is the ratio of the number of particles of the solid composition to the sum of the number of particles of the liquid composition and the number of particles of the solid composition in the observation area at the time point 1.

5. A method for freezing and spraying the composition according to claim 1, wherein the freezing rate is 17% or greater.

6. A method for freezing and spraying a composition according to claim 1, wherein the velocity of the solid composition reaching the target region is 50 m / s or greater.

7. A method for freezing and spraying the composition according to claim 1, wherein the average size of the solid composition present in the observation area is 20 μm to 60 μm.

8. A freeze-spray system for freezing and spraying a composition, comprising: A refrigerant container in which refrigerant is stored at a pressure between 10 bar and 1000 bar; A refrigerant receiving unit configured to receive the refrigerant from the refrigerant container; A nozzle having an opening of a predetermined size and configured to inject the refrigerant, the nozzle pressurizes the refrigerant passing through it, thereby causing the refrigerant passing through the nozzle to expand to atmospheric pressure, and as a result, the temperature of the refrigerant decreases; A composition container containing the aforementioned composition; A composition guide is fluidly connected to the composition container and configured to discharge the composition, the end of which is positioned adjacent to the nozzle, thereby introducing the composition into the refrigerant stream ejected from the nozzle; A valve installed between the refrigerant receiving unit and the nozzle, configured to control the flow of the refrigerant from the refrigerant receiving unit to the nozzle; and A controller configured to control the aforementioned valve; Here, when the refrigerant and the composition are injected from the freezing injection system, the freezing rate, which represents the ratio of the solid state of the composition to the liquid state of the composition, is greater than or equal to 5% at time 1 in the observation area, and Here, the observation area is positioned at an observation distance from the opening of the nozzle and has an arbitrary width. A freeze-injection system equipped with a freeze-injection system.

9. The freezing spray system according to claim 8, wherein the observation area is defined in the side view of the freezing spray system by a first line perpendicular to the central axis of the nozzle, which is located a distance from the opening of the nozzle by the observation distance, and a second line parallel to the first line, which is located a distance of the arbitrary width from the first line.

10. The freeze-injection system according to claim 8, wherein the observation distance is within the recommended injection distance range determined for the mixed injection system.

11. A heat generating unit installed between the refrigerant receiving unit and the nozzle, configured to heat at least a portion of the refrigerant moving from the refrigerant receiving unit to the nozzle; Here, the controller is configured to heat the refrigerant by using the heat generating unit, thereby reducing the freezing rate to 5% or greater. The freeze-injection system according to claim 8, further comprising the following:

12. The controller is configured to apply power within a predetermined power range to the heat generating unit. Here, the heat generation unit generates thermal energy to which the power is applied and which is transferred to the refrigerant. Here, the predetermined power range is set such that the freezing rate is 5% or greater. The freeze-injection system according to claim 11.

13. The freezing rate is the ratio of the number of particles in the solid state of the composition compared with the sum of the number of particles in the liquid state of the composition and the number of particles in the solid state of the composition in the observation area at the time point 1, according to claim 8.

14. The freeze-injection system according to claim 8, further comprising an actuator connected to the composition container and configured to supply the composition to the composition guide.

15. The composition guide includes an input terminal into which the composition flows and an output terminal into which the composition is discharged. Here, the output end of the composition guide is positioned within a predetermined distance from the end of the nozzle. The freeze-injection system according to claim 8.

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