Continuous infusion of therapeutic gas for cosmetic use

Abstract

A system is provided for infusing a gas such as oxygen into a viscous composition, the system having a controlled gap region forming a thin fluid of the viscous composition and a porous gas-infusing delivery element for effectively infusing the gas into the thin fluid as it passes through the controlled gap region.

Description

Attorney Docket No. 129878.00024CONTINUOUS INFUSION OF THERAPEUTIC GAS FOR COSMETIC USECROSS-REFERENCE TO RELATED APPLICATION(S)

[0001] This application claims priority to and the benefit of U.S. Provisional Application No.63 / 765,469, filed February 28, 2025, the entire content of which is herein incorporated by reference.FIELD

[0002] The present application relates to a system and method for effectively infusing a gas such as oxygen into a viscous composition.BACKGROUND

[0003] Skin cells rely on the constant supply of therapeutic gases to maintain function. For example oxygen generates energy to drive the numerous cellular functions for maintaining healthy skin, and healthy looking skin. Oxygen plays a role in breaking down glucose into adenosine tri phosphate (ATP). ATP powers metabolic processes in the body; by driving the synthesis of DNA and RNA, building of proteins, enzymes, and other organisms needed to repair and regenerate cell components; foster cell proliferation; and restore homeostasis. Without oxygen, organisms can split glucose into just two molecules of ATP. With oxygen, cells can produce up to 38 ATP molecules.

[0004] It is known that the superficial surface of the skin, (e.g., up to 0.5 mm in depth) absorbs oxygen not only through vascular blood supply but also from the oxygen in the air. It has been shown that dissolved oxygen will penetrate skin more effectively than gaseous oxygen (Roe et al., 2010, J. Siirg. Res. 159:e29-30; doi: 10.1016 / j jss.2009.10.039. Epub 2009 Nov 21). In addition, topical oxygen is more effective than vascular oxygen supply for superficial skin. Accordingly, cosmetic creams with dissolved oxygen are an effective way of supplying oxygen topically to the superficial surface of the skin.-1- 1103877584\5\AMERICASAttorney Docket No. 129878.00024

[0005] The processes that demand therapeutic gases (e.g. oxygen) include extracellular matrix collagen production, elastin proliferation, general cell metabolism amongst others, all of which are necessary for sustaining healthy, toned, and elastic non-aged appearing skin. The concentration of therapeutic gases in skin is reduced due to intrinsic factors with age due to compromised vasculature and reduced hemoglobin as a result of aging, as well as extrinsic factors such as pollution, sun exposure, smoking, alcohol use, or health related impediments, the risk for which increases with age. As a result, cosmetic or consumer products that improve the supply of therapeutic gases (e. ., oxygen) to the skin surface and improve the content of therapeutic gases in skin layers are desired and are known to improve the appearance of aged skin.

[0006] One strategy for increasing the oxygen content in cosmetic creams is to use materials such as perfluorocarbons that naturally have a high affinity for gasses such as oxygen.Perfluorocarbons are capable of absorbing thirty times as much oxygen as water. This has allowed the development of cosmetic creams that have exemplary performance. However, recent regulations have led to the banning of perfluorocarbons in cosmetics, and so an alternative is required.

[0007] To this end, while oxygen can be readily introduced into perfluorocarbons and water and other low viscosity materials, introducing oxygen into a high viscosity material is not easy or straightforward. The highly viscous nature of many cosmetic formulations prevents oxygen transport throughout the formulation. Increasing viscosity significantly reduces the rate of oxygen diffusion, meaning that as a liquid becomes more viscous, oxygen molecules will move through it more slowly due to increased resistance from the thicker fluid. Essentially higher viscosity acts as a barrier to oxygen movement. The Stokes-Einstein equation defines this fundamental relationship and directly links the diffusion coefficient (a measure of diffusion rate) to viscosity, showing that they are inversely proportional. In other words, as viscosity increases the diffusion coefficient decreases. Accordingly, a need exists for a means of infusing significant quantities of oxygen into viscous cosmetic formulations.-2- 1103877584\5\AMERICASAttorney Docket No. 129878.00024SUMMARY

[0008] The present invention is directed to a system that effectively infuses gas into a composition to form a gas-infused composition. Notably, the system has a controlled gap region forming a thin fluid of the viscous composition on a porous gas-infusing delivery element for effect infusion of the gas into the viscous composition. The system includes a source of the gas (e.g., an oxygen tank or oxygen concentrator), that is in fluid communication with a first container (e.g., a hopper) for containing the composition to be infused, and this first container is either directly connected to (i.e., in direct communication with) a gas-infusing device or is connected through a conduit (e.g., tubing). The gas-infusing device includes a gas delivery element which is a device on which the composition flows over and down its sides. The gas delivery element is connected to a gas source and is porous, such that the gas travels through the element and is emitted out of its porous surfaces. The gas delivery element is configured in the system with an outer wall that forms a controlled gap region around the gas delivery element. The controlled gap causes a thin film of cream to travel past the porous oxygen delivery element allowing for effective oxygen infusion overcoming the limits of oxygen transfer or diffusion that occur when a viscous material is infused with a gas, e.g. oxygen. After the composition passes over the gas delivery element, the gas-infused composition flows into a fill tube and then, or alternatively, into a second container.

[0009] Advantageously, using the disclosed system, a cream composition or a viscous composition is effectively infused with a gas such as oxygen or a gas mixture comprising oxygen. Effective infusion is measured as the gas concentration in the composition over time. Accordingly, a viscous cream composition infused with gas (e.g. oxygen or a mixture comprising oxygen) using the controlled gap system disclosed herein, has an oxygen concentration that is stable (i.e., concentration is the same) for up to about 72 hours after infusion.-3- 1103877584\5\AMERICASAttorney Docket No. 129878.00024BRIEF DESCRIPTION OF THE DRAWINGS

[0010] Figure 1 is a schematic depiction of a system for infusing gas into a viscous composition, the system comprising: a hopper (first container) (1), a pump (2), an a gas-infusion (e.g., oxygenation) device (3), a fill tube (4), a cosmetic (second) container for the gas-infused (e.g., oxygenated) cream (5), a tube (6) connecting the gas-infusion device to a flow regulator (7), a tube (8) connecting the flow regulator (7) to a pressure regulator (9), and a source of gas (10) (e.g., an oxygen tank), according to one or more embodiments of the present invention.

[0011] Figure 2 is a schematic depiction of the system for infusing gas comprising a first container e.g., a hopper) (1), a pump (2), a gas-infusion (e.g., oxygenation) device (3), a tube (6) connecting the gas-infusion device (3) to a flow regulator (7), a tube (8) connecting the flow regulator to a pressure regulator (9), and a source of the gas (10) (e.g., an oxygen tank). A connecting tube (20 or 33) from the oxygenation device (3) leads to a holding tank for the resulting gas-infused (e.g., oxygenated) cream composition (21), according to one or more embodiments of the present invention.

[0012] Figure 3 is a schematic depiction of the system for infusing gas comprising a holding tank or hopper (1), a tube (31) connecting the tank / hopper (1) to a pump (2), a tube (32) connecting the pump (2) to a gas-infusion (e.g., oxygenation) device (3), a tube (6) connecting the gas-infusion device (3) to a flow regulator (7), a tube (8) connecting the flow regulator to a pressure regulator (9), and a source of the gas (10) (e.g., an oxygen tank). Tube (33 or 20) connects the gas-infusion device (3) to a holding tank for the gas-infused composition (21) (e.g., an oxygenated cream), according to one or more embodiments of the present invention.

[0013] Figure 4 is a schematic depiction of the system device (3) for gas infusion (e.g., oxygenation) where the flow of the composition before it is infused with the gas flows from the hopper via a pump in direction (40) towards a threaded attachment input (43). A gas source (10) with a flow regulator (7) and a pressure regulator (9) is connected to the gas-infusion device (3) facilitating flow of gas in direction (41) via the tubing (6) which is connected to a gas delivery-4- 1103877584\5\AMERICASAttorney Docket No. 129878.00024element (44) having a porous sintered body. A controlled gap region (45) is formed between an outer wall (48) configured precisely around the body of the gas delivery element (44), thereby creating a small volume pathway that forces the cream composition to pass over the porous gas delivery element as a thin fluid. The outer wall (48) encompasses the entire body of the gas delivery element except for the input (43) and the output (50). As the thin fluid flows along in the controlled gap region (45), it is exposed to the gas (e.g., oxygen) being emitted from the surface pores on the gas delivery element (44). The thin fluid composition flows in the controlled gap region (45) to the output (50) and into the post-infusion conduit (e.g., tubing or a pipe) (46).Finally, the oxygenated cream flows out of the pipe (46) in direction (42) and into a fill tube (4) (as shown) or through tubing (20, 33), and then from fill tube (4) or the tubing (20, 33) into a second container (21) (not shown), e.g., a cosmetic container, a holding tank, or other vessel, according to one or more embodiments of the present invention.

[0014] Figure 5 depicts a gas-infusion (e.g., oxygenation) system device (3) is as shown in. The gas-infusion device facilitates flow of cream before it is infused with the gas, from a hopper via a pump in direction (40) towards an input (43). A gas source (10) with a flow regulator (7), and a pressure regulator (9) is connected to the gas-infusion device (3) facilitating flow of gas in direction (41) via the tubing (6) which is connected to a rectangular gas delivery element (44) having a porous sintered body. A controlled gap region (45) is formed between the gas delivery element (44) and the upper body of the device, thereby creating a small volume pathway that forces the cream composition to pass over the porous gas delivery element as a thin fluid. The device has a width, and the width and height of the controlled gap region (45) define the cross sectional area of the flowing cream. The length of the device (51) along with the cream flow rate determine the time that cream is exposed to the gas. As the thin fluid flows along in the controlled gap region (45), it is exposed to the gas (e.g., oxygen) being emitted from the surface pores on the gas delivery element (44). The thin fluid composition flows in the controlled gap region (45) and out of the pipe (46) in direction (42) and into a fill tube (4) (as shown) or through tubing (20, 33), and then from-5- 1103877584\5\AMERICASAttorney Docket No. 129878.00024fill tube (4) or the tubing (20, 33) into a second container (21) (not shown), e.g., a cosmetic container, a holding tank, or other vessel, according to one or more embodiments of the present invention.

[0015] In some embodiments of the present invention, the gas-infusion (e.g., oxygenation) device (3) is as shown in Figure 6. The gas-infusion device facilitates flow of cream before it is infused with the gas, from a hopper via a pump in direction (40) towards an input (43). A gas source (10) with a flow regulator (7), and a pressure regulator (9) is connected to the gas-infusion device (3) facilitating flow of gas in direction (41) via the tubing (6) which is connected to two rectangular gas delivery elements (44) having porous sintered bodies. A controlled gap region (45) is formed between the gas delivery elements (44), thereby creating a small volume pathway that forces the cream composition to pass over the porous gas delivery element as a thin fluid. The device has a width, and the width and height of the controlled gap region (45) define the cross sectional area of the flowing cream. The length of the device (51) along with the cream flow rate determine the time that cream is exposed to the gas. As the thin fluid flows along in the controlled gap region (45), it is exposed to the gas (e.g., oxygen) being emitted from the surface pores on the gas delivery elements (44). The thin fluid composition flows in the controlled gap region (45) and out of the pipe (46) in direction (42) and into a fill tube (4) (as shown) or through tubing (20, 33), and then from fill tube (4) or the tubing (20, 33) into a second container (21) (not shown), e.g., a cosmetic container, a holding tank, or other vessel, according to one or more embodiments of the present invention.

[0016] Figure 7 shows measurement of the oxygen content as a function of time for an oxygenated cosmetic cream versus oxygenated distilled water, according to one or more embodiments of the present invention.

[0017] Figure 8 shows measurement of the oxygen content as a function of time for an oxygenated cosmetic cream according to one or more embodiments of the present invention.-6- 1103877584\5\AMERICASAttorney Docket No. 129878.00024

[0018] Figure 9 shows measurement of the oxygen content as a function of time for an oxygenated cosmetic cream treated in Example 1, according to one or more embodiments of the present invention.

[0019] Figure 10 shows measurement of the oxygen content as a function of time for oxygenated distilled water treated with the oxygenation device in Example 4, according to one or more embodiments of the present invention.

[0020] Figure 11 shows a screen shot from a confocal microscope image of an area of skin at between 100 and 300 micron depth on the forearm of a patient before (A) and after (B) treatment with a cream made using an embodiment of the continuous oxygen infusion system of the present invention, according to one or more embodiments of the present invention.

[0021] The foregoing are non-limiting embodiments of the present invention. Other embodiments will be apparent to those skilled in the art.DETAILED DESCRIPTION

[0022] As disclosed herein, the inventors have developed a system device for infusing significant quantities of gas (e.g., oxygen) into cosmetic formulations without using perfluorocarbons.

[0023] The system of the present invention provides a means of infusing significant quantities of oxygen into cosmetic formulations that overcomes the limitations caused by the viscosity of various types of formulations. Such cosmetic formulations include: after-sun creams; anti-aging cream; astringents for cosmetic purposes; body creams; body oils; body scrubs; body sprays; body washes; cosmetics; eye cream; eye gels; facial cleansers; facial moisturizers; facial scrubs; hair conditioners; hair detangling preparations; hair styling spray; hair tonics; hair thinning prevention creams; hair growth stimulating creams; hand cream; lip balm; lip gloss; lip stains; make-up; makeup removing preparations; night cream; sculpting gel; shampoos; skin emollients; skin lotion; skin toners; sun creams; sun tan gel; sun tan lotion; sun tan oil; wrinkle removing skin care preparations;-7- 1103877584\5\AMERICASAttorney Docket No. 129878.00024shaving creams; shaving balms; shaving gels; beard thickening and styling creams and gels; aftershave balms; after-shave creams; after-shave gel; after-shave lotions; bath foam; cosmetic masks; cosmetic skin fresheners; liquid bath soaps; medicated and non-medicated skin care preparations, namely, peels and exfoliates; medicated and non-medicated anti-aging serum and skin clarifiers. Other applicable cosmetic formulations, types, modifications, and changes will be understood by those of ordinary skill in the art without departing from the spirit and scope of the present invention.

[0024] As used herein, the term “about” refers to a reasonable range about a value as determined by the practitioner of skill. In certain embodiments, the term about refers to ± one, two, or three standard deviations. In certain embodiments, the term about refers to ± 5%, 10%, 20%, or 25%. In certain embodiments, the term about refers to ± 0.1, 0.2, or 0.3 logarithmic units.

[0025] The presently disclosed system having a controlled gap region for infusing a gas (e.g. oxygen or a mixture thereof) has the advantage of being able to effectively infuse viscous compositions (e.g. cosmetic creams) with a gas. Nonetheless, a composition of any viscosity may be infused with a gas using the presently disclosed system.

[0026] As used herein, a composition to be infused with gas (e.g. oxygen or a mixture thereof) using the system having a controlled-gap region, is a composition having any viscosity. In some embodiments, a composition to be effectively infused with gas using the disclosed system, is a composition having a viscosity that is not low, and is therefore, above 1,000 centipoise (cP). In some embodiments, the composition to be effectively infused with gas using the disclosed system, is a composition having a viscosity that is not low, and is therefore, above 2,000 centipoise (cP). In some embodiments, the composition to be effectively infused with gas using the disclosed system, is a composition having a viscosity that is not low, and is therefore, above 3,000 centipoise (cP). In some embodiments, the composition to be effectively infused with gas using the disclosed system, is a composition having a viscosity that is not low, and is therefore, above 4,000 centipoise (cP). In some embodiments, the composition to be effectively infused with gas using the disclosed system,-8- 1103877584\5\AMERICASAttorney Docket No. 129878.00024is a composition having a viscosity that is not low, and is therefore, above 5,000 centipoise (cP). In other embodiments, a viscous composition to be infused with gas may range in viscosity from about 1000 cp (e.g. shampoos, liquid foundation) up to 50,000 cP (e.g., thick creams). Accordingly, the viscosity for compositions to be infused with a gas usin the presently disclosed system may range from about 1000 cP to about 50,000 cP; about 2000 cP to about 50,000 cP; about 3000 cP to about 50,000 cP; about 4000 cP to about 50,000 cP; or about 5000 cP to about 50,000 cP.

[0027] In some embodiments, once infused with oxygen, the cosmetic formulations are stored in a package. In additional embodiments, the infused cosmetic formulation is stored in specific packaging such as air-tight packaging. For example, the packaging may include a gas barrier or hermetic seal that retains the higher gas (e.g., oxygen) concentrations in the infused cosmetic formulations than if the infused cosmetic formulations were not stored in packaging having a gas barrier or hermetic seal.

[0028] It is possible to modify a conventional cosmetic fill machine to oxygenate the cream at the point of fill. As shown schematically in Figure 1, cosmetic cream is loaded into a first container, the hopper (1). Cream is dispensed by means of a metering pump (2) through an oxygenation device of the invention (3) through the fill tube (4), and after oxygenation, into a second container, the cosmetic container (5). Oxygen gas (9) is supplied to the oxygenation chamber through a pressure regulator (8) and a flow meter (7), allowing the pressure and flow rate of the gas to be controlled. While the use of a gas cylinder as the source of gas is shown in this example, other sources, such as oxygen concentrators could also be used.

[0029] Examples of the gas-infusion device (3), the gas delivery element (44), and a source of gas (10) include the oxygenation device (3), the oxygen delivery element (44), and the oxygen tank (10). Where the oxygenation device (3) or the oxygen delivery element (44) is disclosed herein, the context and configurations apply to all therapeutic gases. The following description refers to these features for a system infusing oxygen. However, the features and use of the system to effectively infuse a therapeutic gas into a viscous cream composition for cosmetic use are the same-9- 1103877584\5\AMERICASAttorney Docket No. 129878.00024irrespective of the type of therapeutic gas to be infused. Examples of therapeutic gases for cosmetic compositions include oxygen, carbon dioxide, ozone, nitrogen, hydrogen sulfide, nitric oxide, xenon, hydrogen, or any suitable mixture thereof. Accordingly, terms “gas-infusing device” and “gas infusion device” are interchangeable with “oxygenation device”. The terms “oxygen delivery element” (including “porous oxygen delivery element”) is interchangeable with gas delivery element. Similarly, where the term “oxygen” is used herein, the context and disclosure also applies to any therapeutic gas.

[0030] Figure 1 shows the hopper (1), pump (2), oxygenation device (3), and fill tube (4) connected directly to (i.e. in direct communication with) each other; however, as one skilled in the art would recognize, the hopper, pump, oxygenation device, and fill tube could also be connected together via one or more conduits (e.g., tubing) in between each or some of the features, to render different spatial arrangements of the fill apparatus.

[0031] A surprising finding from this development is that by infusing oxygen into a cosmetic cream using the oxygenation device of this invention, the oxygenation is stable within the cream for up to 70 hours, as shown in Figures 7 and 8 and discussed below. This finding provides an alternative arrangement for preparing oxygenated cosmetics of this invention whereby the cream is oxygenated as a separate operation from the mixing of the rest of the formulation and the fill of cosmetic containers with the oxygenated cream. Cosmetic fill lines can be very complex and expensive. Advantageously, the present disclosed oxygenation system allows for existing mixing and filling equipment to be used without modification.

[0032] An additional benefit of performing the oxygenation as a separate process is that it can be a continuous process with a uniform cream flow rate. This allows the oxygenation parameters to be set for optimum oxygenation. By contrast the unit dosing of a fill line means that the cream flow rate varies between zero to a maximum and back to zero as each container is filled. It is thus more difficult to define optimum infusion parameters.-10- 1103877584\5\AMERICASAttorney Docket No. 129878.00024

[0033] Figure 2 shows a cosmetic cream loaded into the hopper (1). Cream is transported by a pump (2) through an oxygenation device of the invention (3) through tubing (20), and into a holding tank (21). Oxygen gas in a gas cylinder (10) is supplied to the oxygenation device (3) through a pressure regulator (9) and a flow meter (7), allowing the pressure and flow rate of the gas to be controlled. While the use of a gas cylinder as the source of gas is convenient, other sources such as oxygen concentrators could also be used.

[0034] Figure 3 shows a cosmetic cream loaded into the hopper (1). Cream is transported through tubing (31) by a pump (2), connected by tubing (32) to an oxygenation device of the invention (3) and then through tubing (33), into a holding tank (21). Oxygen gas in a gas cylinder (10) is supplied to the oxygenation device (3) through a pressure regulator (9) and a flow meter (7), allowing the pressure and flow rate of the gas to be controlled. While the use of a gas cylinder as the source of gas is convenient, other sources such as oxygen concentrators may be used.

[0035] Additionally, any suitable pump may be used. In preferred examples, a peristaltic pump or a gear pump are used, both of which are capable of providing a uniform flow rate.

[0036] Figure 4 shows an oxygenation device of the invention (3). A connector (43), optionally threaded, connects either directly to the pump (2) or (12) or to tubing (10), as shown in Figures 1 to 3. The cream enters the device in the direction (40) at the threaded input (43) and the flow path through the device includes a region with a controlled gap (45) formed between the outer wall (48) and the oxygen delivery element in which the composition is forced into a thin fluid that flows on and around the porous oxygen delivery element (44). Oxygen is delivered to this element by tubing (6), as shown in Figures 1, 2, and 3. The thin fluid cream is oxygenated as it flows along the oxygen delivery element (44) and leaves the controlled gap at output (50) and flows into post-infusion conduit (46) to a second container (e.g., fill tube) (4) as shown, or could be from post-infusion conduit (46) into tubing (20 or 33) for transport into a holding tank.

[0037] The porous oxygen delivery element (44) is a key aspect of the invention and is preferably fabricated from sintered stainless steel to provide a porosity ranging from 0.5 microns to-11- 1103877584\5\AMERICASAttorney Docket No. 129878.0002420 microns. Preferably the porosity is in the range of 0.5 to 2.0 microns. While stainless steel is the preferred material of construction other materials suitable for food contact, or medical use, such as engineered plastics may also be used.

[0038] The controlled gap (45) is a critical element of the oxygenation device of the present invention. The controlled gap (45) causes the cream to travel past the porous oxygen delivery element as a thin fdm that allows for the effective oxygen infusion that this device provides, thereby, overcoming the limits of oxygen transfer or diffusion that occur when a viscous material is infused with a gas, e.g. oxygen. Upon flow of the cream composition through the system, the height of the controlled gap region from the pores on the surface of the oxygen delivery device (44) to the outer wall (48) fdls with the cream composition and is the distance the oxygen travels through the composition. Accordingly, the width of the controlled gap region, is in this example the circumference of the cylindrical oxygenation element, and the width together with the height of the gap defines the cross-sectional area of the flowing cream.

[0039] In some embodiments, the height of the controlled gap region is from about 0.5 mm up to about 1 cm. In some embodiments the height of the controlled gap ranges from about 0.5 mm to about 9 mm, about 0.5 mm to about 8 mm, about 0.5 mm to about 7 mm, about 0.5 mm to about 6 mm, about 0.5 mm to about 5 mm, about 0.5 mm to about 4 mm, about 0.5 mm to about 3 mm, about 0.5 mm to about 2 mm, or about 0.5 mm to about 1 mm. In some embodiments, the height of the controlled gap ranges from about 0.5 to about 5 mm. In other embodiments, the height of the controlled gap ranges from about 0.5 to about 3 mm.

[0040] In some embodiments, the width of the controlled gap ranges from about 5 mm to about 200 mm, about 10 mm to about 100 mm, about 15 mm to about 50 mm, about 0.5 mm to about 60 mm, about 0.5 mm to about 50 mm, about 0.5 mm to about 40 mm, about 0.5 mm to about 30 mm, about 0.5 mm to about 25 mm, about 0.5 mm to about 20 mm, about 0.5 mm to about 15 mm, about 0.5 mm to about 10 mm, about 0.5 mm to about 9 mm, about 0.5 mm to about 8 mm, about 0.5 mm to about 7 mm, about 0.5 mm to about 6 mm, about 0.5 mm to about 5 mm, about 0.5 mm-12- 1103877584\5\AMERICASAttorney Docket No. 129878.00024to about 4 mm, about 0.5 mm to about 3 mm, about 0.5 mm to about 2 mm, or about 0.5 mm to about 1 mm. In some embodiments, the width of the controlled gap ranges from about 0.5 to about 5 mm. In other embodiments, the width of the controlled gap ranges from about 0.5 to about 3 mm.

[0041] The flow rate of the cream and the length of the oxygenation device define the time for oxygen infusion. In some embodiments the length of the oxygenation device ranges from 1 cm to about 30 cm. In some embodiments the length ranges from 2 cm to about 20 cm, about 3 cm to 10 cm, 4 cm to 6 cm.

[0042] Notably, the rate at which cosmetic formulations (e.g., creams, etc.) to be oxygenated are pumped through the oxygenation device depend on: 1) viscosity of the formulation composition, 2) the volume of the controlled gap region, and 3) the dimensions of the gap. The more viscous the composition and the smaller the gap, the higher the required pressure in the system that the pump will need to overcome. The pressure will also act to counter the pressure of the oxygen, which must be higher than the internal pressure in the composition for oxygen to be infused therein.

[0043] The porous oxygen delivery element may be of any suitable shape. With reference to Figure 4, in some embodiments, the porous oxygen delivery element (44) is cylindrical with a diameter of about 5 mm to about 25 mm, and preferably with a diameter between 8 mm and 12 mm. The length of the oxygen delivery element is between about 10 mm and about 100 mm, and preferably the length is between about 15 mm and about 45 mm.

[0044] In an alternative embodiment, with reference to Figure 5, the porous oxygen delivery element (44) has a rectangular or rectangular prism shape wherein the controlled gap region (45) is formed as a slot above it, being defined by an outer wall and the surface of the oxygen delivery element (44). The width, height, and length dimensions of the controlled gap region (45) for the cylinder and rectangular are the same.-13- 1103877584\5\AMERICASAttorney Docket No. 129878.00024

[0045] With reference to Figure 6, in an additional embodiment, the gas-infusing device has two porous oxygen delivery elements (44) forming the slot region (i.e., controlled gap region) so that gas (e. ., oxygen) is delivered from both surfaces into the controlled gap region (45).

[0046] The oxygenation device may also contain multiple porous oxygen delivery elements, or multiple oxygenation devices can be connected together in series. The device may also incorporate sleeves to allow the gap to be easily changed.

[0047] The level of oxygenation is controlled by the pressure and flow rate of the oxygen. The oxygen pressure is controlled to be between 15 psi and 120 psi, preferably between 30 psi and 50 psi. The flow rate of oxygen is controlled to be between 0.5 L / min and 3.0 L / min, preferably between 1.0 and 2.0 L / min.

[0048] Some embodiments of the present invention include a cosmetic composition that is suitable for infusion with a therapeutic gas and methods for gas infusion. The use of emulsified formulations provides materials that are pleasing to the skin and may be spread over, and / or absorbed into the skin.

[0049] A surprising finding of the use of the device of this invention is shown in Figure 7 where the oxygen content of a cosmetic cream is approximately 24.3 mg / L and distilled water oxygenated by the process of this invention are compared. The oxygenated materials are placed in vials exposed to the atmosphere and as expected the oxygen content of the distilled water drops with time back to its starting point as the oxygen in the water equilibrates with the atmosphere. In contrast the cream is infused with oxygen to a higher content and that content remains stable with time. The longevity of this stability is further shown in the example in Figure 8 where stability is shown for up to more than 70 hours (about 72 hours). Accordingly, a cream composition infused with 19 mg / L oxygen (O2), retains this concentration of oxygen for about 72 hours or about 3 days. The fluctuations seen are thought to be due to fluctuations in the temperature of the laboratory.

[0050] A number of different therapeutic gases may be used for infusion into a cosmetic composition. Examples of therapeutic gases for cosmetic compositions include oxygen, carbon-14- 1103877584\5\AMERICASAttorney Docket No. 129878.00024dioxide, ozone, nitrogen, hydrogen sulfide, nitric oxide, xenon, hydrogen, or any suitable mixture thereof.

[0051] The term “skin” as used in this invention indicates any skin tissue on the entire body including the face, neck, scalp, hands, feet, and other skin areas.

[0052] The terms cosmetic, cosmetic composition, cosmetic formulation, cosmetic cream, cream, formulation and composition are used interchangeably and denote a material designed to be applied to the skin such as on the face, scalp, hair follicles, or hair. As used herein, in addition to creams and ointments, the cosmetic composition may also include a washing fluid or washing solution having water as its most abundant component.

[0053] While the delivery of oxygen is an embodiment of this invention, other gases or mixtures of gases with therapeutic benefit may be added to or substituted for oxygen.

[0054] The emulsifying agent may be a non-fluorinated chemical or compound such as hydrogenated phospholipids including, but not limited to, hydrogenated phosphatidylcholine, phosphatidylserine, phosphatidylinositol, phosphanolipids, phosphatidic acid, and other mixtures thereof

[0055] Non-limiting examples of dispersing agents include glycerols, phospholipids, lecithins, surfactants, and / or polyoxamers.

[0056] Cosmetic compositions may include other suitable ingredients designed to provide specific benefits to the user’s skin. Suitable ingredients include anti-ageing molecules, those that promote moisturization, components that improve the texture and feel of the cosmetic, and components that provide scent to the cosmetic.

[0057] Additives to the cosmetic formulation include emollients, anti-oxidants, and essential oils. Non-limiting examples include aloe vera, collagen, glyceryl stearate, capric triglyceride, stearic acid, shea butter, cetyl alcohol, pentylene glycol, propanediol, tranexamic acid, camellia oleifera, myristyl myristate, phenoxyethanol, cyclopentadecanolide, hydroxyethyl acrylate, hyaluronic acid, gellan, carbomer, and alginate.-15- 1103877584\5\AMERICASAttorney Docket No. 129878.00024

[0058] In some embodiments, the gas for saturation of a cream formulation is oxygen.However, in additional embodiments, other gases may be infused into the cream formulation. In further embodiments, other gases may be mixed with oxygen and the gas mixture is infused into the cream formulation. Other gases include any suitable gas, for example, hydrogen, which has antioxidant properties, that is beneficial for skin.

[0059] A source of gas may be in any suitable form. For example, the source of gas may be a gas cylinder or canister.

[0060] The source of gas may also be an oxygen concentrator that uses a filter to remove nitrogen from compressed air, thus increasing the oxygen concentration. Such devices are regularly used for individuals who need help with their breathing.

[0061] While it is essential to use the device of this invention to infuse oxygen into viscous cosmetic formulations it is also possible to use the device for low viscosity formulations. It is possible to oxygenate, or gas saturate a number of different cosmetic formulations that may be utilized for different purposes. So, for example, a washing water having a high proportion of water could be treated for use as an oxygenated cleanser, for skin or hair.

[0062] In some embodiments of the present invention, the infusion apparatus design includes a user interface that controls the gas valve to regulate the concentration of the gas and / or ratio of gases (e.g., oxygen, nitrogen, carbon dioxide, hydrogen) used to impregnate the cream.

[0063] While the main focus of this invention is on the oxygenation of formulations during manufacture it will be readily apparent to those skilled in the field that the oxygenation device also has applicability for the oxygenation of cosmetic formulations at the point of use, e.g. in a salon or at home.

[0064] The following Examples are presented for illustrative purposes only, and do not limit the scope or content of the present application.-16- 1103877584\5\AMERICASAttorney Docket No. 129878.00024

[0065] Example 1. A cosmetic cream was formulated with water, glyceryl stearate, stearic acid, caprylic / capric triglyceride, glycerin, pentylene glycol, cetyl alcohol, coco-caprylate / caprate, butyrospermum parkii (shea) butter, tranexamic acid, camellia oleifera (camellia) seed oil, palmitoyl tripeptide-1, palmitoyl tetrapeptide-7, acetyl hexapeptide- 8, pentapeptide- 18, sodium hyaluronate, phenoxyethanol, dipropylene glycol, tocopheryl acetate, tetrasodiumiminodi succinate, tetrahexyldecyl ascorbate, pentadecalactone, and citric acid. The oxygen content of the cream was monitored using a PreSens Microx 4 oxygen sensor placed into the cream. Prior to oxygenation the oxygen content was 6.5 mg / L. An oxygenation apparatus with a set-up following the scheme in Figure 2 was used: wherein a peristaltic pump was set at 280 ml / min, an oxygenating element with 0.5 micron porosity was used along with an oxygen pressure of 45 psi and a flow rate of 1.5 L / min. The oxygen content was measured at 32.3 mg / L at 1 hour post infusion and the oxygen content versus time is shown graphically in Figure 9.

[0066] Example 2. A cosmetic cream was formulated with water, niacinamide, glycerin, pentyl ene glycol, acetyl hexapeptide-8, pentapeptide- 18, palmitoyl tripeptide-5, palmitoyl dipeptide-5, hydrolyzed hyaluronic acid, sodium hyaluronate, resveratrol, carnosine, allantoin, sodium carboxymethyl beta-glucan, hydrolyzed soy protein, rice amino acids, aloe barbadensis leaf juice powder, hydrolyzed adansonia digitata seed extract, silybum marianum fruit extract, phenoxyethanol, sodium hydroxide, sodium benzoate, carbomer, panthenol, hydroxy ethyl cellulose, alcohol, tetrasodium iminodisuccinate, lecithin, proline, tetradecyl aminobutyroylvalylaminobutyric urea trifluoroacetate, diaminobutyroyl hydroxythreonine, magnesium chloride, and tocopherol. The oxygen content of the gas phase of the cream was monitored using a PreSens Microx 4 oxygen sensor placed into the cream. Prior to oxygenation treatment the oxygen content of the cream was 6.5 mg / L. The oxygenation apparatus of Example 1 was used with a 1 mm gap, a cream flow rate of 230 g / min, an oxygen pressure of 45 psi and flow rate of 1.5 L / min. The oxygen content of the cream measured one hour after oxygenation was 26.4-17- 1103877584\5\AMERICASAttorney Docket No. 129878.00024mg / L.

[0067] Example 3. A cosmetic cream was made with the following ingredients: water, aloe barbadensis (aloe vera) leaf powder, stearic acid, glycerin, propanediol, glyceryl stearate se, cetyl alcohol, phenoxyethanol, caprylic / capric triglyceride, tetrasodium EDTA, tocopheryl acetate, sodium hydroxide, and manganese gluconate. The oxygen content of the gas phase of the cream was monitored using a PreSens Microx 4 oxygen sensor placed into the cream. Prior to oxygenation treatment, the oxygen content of the cream was 9.5 mg / L. The oxygenation apparatus of Example 1 was used with a 1 mm gap, a range of cream flow rates, an oxygen pressure of 45 psi, and a flow rate of 1.5 L / min. The oxygen content of the cream measured one hour after oxygenation is shown in Table 1 for a range of flow rates.Table 1.

[0068] Example 4. Distilled water was treated using the oxygenation apparatus of Example 1. The oxygen content of the water was 8 mg / L as measured using a PreSens Microx 4 oxygen sensor. The oxygenation apparatus of Example 1 with a 1 mm gap was then used to oxygenate the water at a water flow rate of 260 g / min. The oxygen pressure was 45 psi and the flow rate was 1.5 L / min. The peak oxygen content measured in the oxygenated water was 23.6 mg / L. However, as can be seen from the data in Figure 10 the oxygen content dropped rapidly with time.-18- 1103877584\5\AMERICASAttorney Docket No. 129878.00024

[0069] Example 5. An area on the forearm of a subject was imaged at between 150 and 500 micron (pm) depth using a confocal microscope. Then a cosmetic cream made using the methods outlined in the present invention was applied to the same area on the forearm of the subject and further images were obtained at between 150 and 500 micron depth at 5 minutes post-application. With reference to Figure 11, comparing the control in panel (A) to the treated skin in panel (B), there is increased blood flow, blood vessel density, and blood vessel diameter in the treated skin, as indicated by the increased brightness of the blood vessel in the circled area, whereas the control creams without oxygen infusion have lower blood flow, blood vessel density, and blood vessel diameter. Similar results were seen regardless of the other active ingredients in the cream tested, where increased blood flow was seen in the skin when it was infused with oxygen according to the present invention.

[0070] While the present invention has been illustrated and described with reference to certain exemplary embodiments, those of ordinary skill in the art will understand that various modifications and changes may be made to the described embodiments without departing from the spirit and scope of the present invention, as defined in the following claims.-19- 1103877584\5\AMERICAS

Claims

Attorney Docket No. 129878.00024WHAT IS CLAIMED IS:

1. A system for infusing gas into a viscous composition to form a gas-infusedcomposition, the system comprising:a source of the gas;a first container holding a quantity of the viscous composition;a gas-infusing device positioned downstream of the first container forreceiving a flow of the cream composition, the gas-infusing device comprising:a gas delivery element in fluid communication with the source ofgas, thereby receiving gas, the gas delivery element having pores on itsouter surface that emit the gas;and a controlled gap region, formed between the outer surface ofthe gas delivery element and an outer wall, the outer wall beingpositioned a distance from the outer surface, thereby forming thecontrolled gap region;a means for providing gas to the gas-infusing device;a second container positioned downstream of the gas-infusing device,the second container for receiving the viscous composition after it passes fromthe gas-infusing device; anda means for actuating flow of the viscous composition through thesystem from the first container to the gas-infusing device to the secondcontainer.

2. A system for infusing oxygen into a cream composition to form anoxygen infused composition, the system comprising:a source of oxygen;a first container holding a quantity of the cream composition;an oxygenation device positioned downstream of the first container forreceiving a flow of the cream composition, the oxygenation device comprising:-20- 1103877584\5\AMERICASAttorney Docket No. 129878.00024an oxygen delivery element in fluid communication with thesource of oxygen, thereby receiving oxygen, the oxygen deliveryelement having pores on its outer surface that emit the oxygen;and a controlled gap region, formed between the outer surface ofthe oxygen delivery element and an outer wall, the outer wall beingpositioned a distance from the outer surface, thereby forming thecontrolled gap region;a means for providing oxygen to the oxygenation device;a second container positioned downstream of the oxygenation device,the second container for receiving the cream composition after it passes fromthe oxygenation device; anda means for actuating flow of the cream through the system from the firstcontainer to the oxygenation device to the second container.

3. The system of any one of claims 1 or 2, wherein the controlled gap has aheight in a range from about 0.5 mm to about 5.0 mm.

4. The system of any previous claim, wherein the controlled gap has a width ina range from about 0.5 mm to about 5.0 mm.

5. The system of any previous claims, wherein the oxygenation device or thegas-infusing device has a length in a range from about 1 cm to about 30 cm.

6. The system of any previous claim, wherein the porosity of the one or moreside walls is in a range of about 0.5 microns to about 20 microns.

7. The system of any previous claim, wherein the porosity of the one or moreside walls is in a range of 0.5 microns to about 2.0 microns.

8. The system of any previous claim, wherein the viscous composition or thecream composition has a viscosity of at least 1,000 centipoise (cP).-21- 1103877584\5\AMERICASAttorney Docket No. 129878.000249. The system of claim 8, wherein the cylindrical shape has a diameter of about5 mm to about 25 mm.

10. The system of claim 8, wherein the cylindrical shape has a diameter of about8 mm to about 12 mm.

11. The system of any previous claim, wherein the oxygen delivery element orthe gas-delivery element has a length in a range of about 10 mm to about 100mm.

12. The system of any previous claim, wherein the oxygen delivery element orthe gas-delivery element has a length in a range of about 15 mm to about 45mm.

13. The system of any previous claim, wherein the second container comprisesa gas barrier.

14. The system of any previous claim, wherein the first container is in direct communication with the oxygenation device or the gas-infusing device and theoxygenation device or the gas-infusing device is in direct communication withthe second container.

15. The system of any of claims 1-13, further comprising an enclosed firstconduit connecting the first container to the oxygenation device or the gasinfusing device, wherein the conduit is for transporting the cream.

16. The system of any of claims 1-13, further comprising an enclosed secondconduit connecting the oxygenation device or the gas-infusing device to thesecond container, wherein the second conduit is for transporting the cream.-22- 1103877584\5\AMERICASAttorney Docket No. 129878.0002417. The system of any of claims 1-13, further comprising an enclosed firstconduit connecting the first container to the oxygenation device or the gasinfusing device and an enclosed second conduit connecting the oxygenationdevice or the gas-infusing device to the second container, wherein the first andsecond conduits are for transporting the cream.

18. The system of any previous claim, wherein the means for actuating flow ofthe cream is a pump.

19. The system of claim 18, wherein the pump is in direct communication withthe first container.

20. The system of any previous claim, further comprising a flow regulator forregulating the flow of gas or oxygen from the source of gas or oxygen to the gasdelivery element or the oxygen delivery element.

21. The system of any previous claim, wherein the means for providing oxygento the oxygenation device is a conduit suitable for transporting oxygen from thesource of oxygen to the oxygen delivery element.

22. The system of claim 21, wherein the conduit is tubing.

23. A system for infusing gas into a viscous composition to form a gas-infusedcomposition, the system comprising:a source of the gas;a first container holding a quantity of the viscous composition;a gas-infusing device positioned downstream of the first container forreceiving a flow of the cream composition, the gas-infusing device comprising:at least one gas delivery element in fluid communication with thesource of gas, thereby receiving gas, the at least one gas delivery elementhaving pores on its outer surface that emit the gas;-23- 1103877584\5\AMERICASAttorney Docket No. 129878.00024and a controlled gap region, formed:(i) between an outer wall and the at least one gasdelivery element; or(ii) between two gas delivery elements;a means for providing gas to the gas-infusing device;a second container positioned downstream of the gas-infusing device,the second container for receiving the viscous composition after it passes fromthe gas-infusing device; anda means for actuating flow of the viscous composition through thesystem from the first container to the gas-infusing device to the secondcontainer.

24. The system of claim 23, wherein the at least one gas delivery elementhas a rectangular or rectangular prism shape.

25. The system of claim 23 or claim 24, wherein the gas-infusing device isan oxygenation device and the at least one gas delivery element is an oxygendelivery element.

26. The system of any one of claims 23-25, wherein the controlled gap hasa width in a range from about 0.5 mm to about 5.0 mm.

27. The system of any one of claims 23-26, wherein the controlled gap hasa height in a range from about 0.5 mm to about 5.0 mm.

28. The system of any one of claims 23-27, wherein the oxygenation deviceor the gas-infusing device has a length in a range from about 1 cm to about 30cm.

29. The system of any one of claims 23-28, wherein the porosity of the oneor more side walls is in a range of about 0.5 microns to about 20 microns.-24- 1103877584\5\AMERICASAttorney Docket No. 129878.0002430. The system of any one of claims 23-29, wherein the porosity of the oneor more side walls is in a range of 0.5 microns to about 2.0 microns.

31. A viscous composition or a cream composition infused with gas oroxygen using the system of any one of claims 1-22.

32. The viscous composition or cream composition of claim 31 , wherein thegas or oxygen concentration infused therein is the same from the time of infusionup to about 72 hours.

33. A viscous composition infused with a gas using the system of any one ofclaims 23-29.

34. The viscous composition of claim 33, wherein the viscosity is at least1,000 centipoise (cP).

35. The viscous composition of any one of claims 33-34, wherein the gascomprises oxygen.

36. The viscous composition of claim 35, wherein the concentration ofoxygen is the same from the time of infusion to about 72 hours.-25- 1103877584\5\AMERICAS

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