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Title:
NEEDLELESS INJECTION DEVICE FOR IN-SITU REACTION
Document Type and Number:
WIPO Patent Application WO/2021/089163
Kind Code:
A1
Abstract:
The invention relates to a system for a needleless injection device including at least one composition aimed at generating an in-situ reaction into the skin, scalp, or lips and at least a needless injection device.

Inventors:
BURNIER VÉRONIQUE (FR)
BORDEAUX DOMINIQUE (FR)
Application Number:
PCT/EP2019/080595
Publication Date:
May 14, 2021
Filing Date:
November 07, 2019
Export Citation:
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Assignee:
OREAL (FR)
International Classes:
A61M5/30; A61J1/10; A61K9/00; A61M5/31
Domestic Patent References:
WO2001089613A12001-11-29
Foreign References:
FR3078489A12019-09-06
US20110015567A12011-01-20
US8876758B22014-11-04
US9186461B22015-11-17
US8066661B22011-11-29
US20160129191A12016-05-12
US8734384B22014-05-27
US9265888B22016-02-23
Other References:
B. LARSEN ET AL.: "Rheological characterization of an injectable alginate gel system", BMC BIOTECHNOLOGY, 2015, pages 15 - 29
Attorney, Agent or Firm:
BOURDEAU, Françoise (FR)
Download PDF:
Claims:
CLAIMS

1. A system for a needle less injection device, characterized in that it includes at least one composition aimed at generating an in-situ reaction into the skin, scalp, or lips and at least a needless injection device.

2. A system according to claim 1, characterized in that the needless injection device is a gas-pressure-actuated needleless device.

3. A system according anyone of the preceding claims, characterized in that the device comprises:

- a nozzle head (320) with a composition input hole and a distinct injection hole,

- a cartridge that is connected to said nozzle head (320) and is adapted to provide the nozzle head (320) with one or multiple doses of composition for injection;

- an injection head comprising a first mechanism for releasing a dose of composition from said cartridge to said nozzle head (320) and a second mechanism for injecting said dose of composition from said nozzle head (320) into the skin, scalp, or lips of a person.

4. A system according to claim 3, characterized in that the second mechanism exerts a high pressure on the composition.

5. A system according to claim 1, characterized in that the needless injection system includes at least a container comprising a composition that is to be injected, the container being separated from the device.

6. A system according anyone of the preceding claims, characterized in that the composition is a fluid composition containing at least one material in the dispersed state in a liquid medium, said composition being solidifiable via the reaction of said material into the skin, scalp, or lips.

7. A system according anyone of the preceding claims, characterized in that it comprises a first composition comprising a carbonate solution, and a second composition comprising an alginate.

8. A method for preparing an injection of a composition aimed at generating an in-situ reaction into an area of skin, scalp, or lips for correcting a relief or appearance of this area, the injection being performed with the device as defined in any one of the preceding claims, the method comprising: - performing an acquisition of the topography of the area, preferably an optical acquisition, and

- based on such acquisition of the topography, computing a volume of composition to inject into the skin, scalp, or lips.

9. The method of the preceding claim, wherein the composition comprises at least one bio-polymer and an ion solution, the latter being mixed before their injection into the skin, scalp, or lips.

10. The method of any one of claims 8 or 9, wherein the composition comprises at least one bio-polymer and an ion solution, the latter being stored in different containers and separately injected, preferably with a ratio of 50 % each.

Description:
NEEDLELESS INJECTION DEVICE FOR IN-SITU REACTION

Technical field

The present invention relates to a cartridge for a needleless injection device, to a needleless injection system and to a method for the treatment, notably cosmetic treatment, of human keratin materials.

Background art

Publications US 8876758 B2, US 9186461 B2, US 8066661 B2, US 20160129191 Al, US 8734384 B2 and US 9265888 B2 disclose needleless injectors comprising a reservoir containing a gas, a chamber containing a piston and a viscous liquid formulation that is to be injected, the chamber communicating with an injection nozzle.

Such needleless injectors require, once the chamber is empty, the chamber to be replaced or refilled, notably manually, so that they can become usable again.

Such needleless injectors have an injection nozzle the geometry and dimensions of which are fixed, thereby limiting the formulations that can be used, notably in terms of viscosity. That may lead, on the one hand, to limitations on the treatments that can be carried out and, on the other hand, to a loss of formulation at the start of injection.

For example, in order to treat wrinkles, there are various products currently available on the market, such as hyaluronic acid or Botox, which have different rheologies. Thus, the one same needleless injector as described hereinabove cannot be used for injecting both these two products since the geometry and the dimensions of the injection nozzle, notably the size of its outlet orifice, needs to be tailored to suit the product that is to be injected. Since the viscosity of the product and or the polymer structure would not make possible using needleless injectors

There is consequently still a need to further improve the injection of a product into the human keratin materials using a needleless injector, notably in order to prevent, treat and/or reduce a relief and/or a fold in an area of skin and/or a skin-colour disorder.

The filling is primarily for the attenuation of facial wrinkles, the main consequence of aging of the skin. This technique can also correct hollow irregularities or depressions of the skin, by restoring its volume by injecting a so-called filling product. In the vast majority of cases, dermatologists use resorbable fillers, particularly hyaluronic acid. It helps to fill in fine wrinkles, around the mouth for example, but also deeper wrinkles like nasolabial folds. Hyaluronic acid can also be used to give the cheekbones volume when they are hollow, fill in dark circles, redraw and give volume to the lips. Other bio-compatible polymers are being used like polylactic acid.

To fill a wrinkle, the product is injected into the thickness of the skin, while using syringe and needles in the middle or deep dermis depending on the type of product used. When it comes to restoring volume, the injection takes place under the skin and sometimes even sub- muscular. The product has a first action related to the volume of the injected product which, by its mere presence under the skin, inflates it and generates a volume.

In addition, the hydrophilic character of its components attracts water molecules that also contribute to the restoration of volumes. The more the filling product is fluid, the higher it is put it in the dermis. The thicker the product, the more it will be injected deeply. Fillers that aim to restore a large volume can sometimes be injected into contact with the bone, in muscle. The main difficulty to inject fillers inside skin comes from their consistency related mainly to the G' rheological parameter: The higher is G the more difficult the possibility to transfer fillers.

Complex shear modulus G*

Definition of the law of elasticity for oscillatory shear tests:

G* = tA / gA with complex shear modulus G* (G star, in Pa), shear-stress amplitude tA (in Pa), and strain amplitude gA (dimensionless, or expressed in %). G* describes the entire viscoelastic behavior of a sample and is called the complex shear modulus G*.

Storage modulus G and loss modulus G’

The phase shift d, which is the time lag between the preset and the resulting sinusoidal oscillation is determined for each measuring point. This angle, always between 0° and 90°, is now placed below the G* vector.

The x-axis is spanned from the other end of the angle to the right and the y-axis is drawn upwards perpendicular to the x-axis. The part of the G* value that runs along the x- axis is the elastic portion of the viscoelastic behavior presented as G while the part of the G* vector that is projected onto the y-axis is the viscous portion G'. There is still a need to generate in-skin reactions, that is to say to transfer, in at least one superficial layer of the skin, at least two substance s-compounds and/or compositions that are able to react together to generate at least, totally or partially, a third compound and/or composition after at least a reaction between them.

There is a need for improving the delivery of cosmetic compositions into the skin, scalp, or lips, especially the precision of the amount of delivered composition and the control of the depth of injection into the skin at the targeted location.

Disclosure of the invention

The present invention aims to further perfect the systems used to treat human keratin materials, such as the skin, and notably to overcome the above drawbacks. It achieves this by virtue of a system for a needleless injection device, characterized in that it includes at least one composition aimed at generating an in-situ reaction into the skin, scalp, or lips and at least a needless injection device.

What is meant by a “needleless injection device” is a device in which injection is achieved without an injection needle penetrating through the epidermis.

Preferably, the needless injection device is a gas-pressure-actuated needleless device.

Using the system of the invention offers a long lasting solution for skin ageing signs and disorders correction, by improving skin penetration of such composition. The diffusion and reaction of the composition into the skin is eased by the use of a needleless injection devices.

Needleless injection devices improve skin penetration of bio- polymers, for example alginate solutions, of compositions and/or of active compounds solutions, as calcium carbonate solutions, to generate an in-situ aggregation or precipitation allowing a film/mesh formation. Compositions are delivered to the appropriated depth of the skin, that is to say to targeted skin layers.

Compositions are delivered deeper inside skin, by-passing and going through the stratum corneum (SC) layer.

The system according to the invention allows targeting and delivering resorbable, injectable tensile, swelling or firming compositions aimed at generating an in- situ reaction into upper skin layers, in a homogenous way, to correct, supply volume, soften and/or erase skin ageing signs disorders, such as wrinkles, skin creases, especially facial creases, skin depressions, loss of elasticity, firmness, or hydration, modifications of the appearance of skin, modifications of the face oval, especially shallow contours, or the sagging of certain areas.

The delivery and diffusion of tensile, swelling or firming compositions is possible, even by reaching deep layers, which is not possible with topical applications. The invention facilitates the injection of bio-cosmetic compositions that aim at generating an in- situ reaction into the skin, scalp, or lips, especially for forming in-situ compositions of increased viscosity.

What is meant by “skin ” is the dermis and the epidermis and the superficial region of the mucous membranes such as the lips.

The invention offers an easy-to-use, reliable, robust, compact and ergonomic solution for the needleless injection of a composition.

Nee dieless inje ction de vice

According to a first embodiment of the invention, the device comprises:

- a nozzle head with a composition input hole and a distinct injection hole,

- a cartridge that is connected to said nozzle head and is adapted to provide the nozzle head with one or multiple doses of composition for injection;

- an injection head comprising a first mechanism for releasing a dose of composition from said cartridge to said nozzle and a second mechanism for injecting said dose of composition from said nozzle into the skin, scalp, or lips of a person.

Advantageously, the second mechanism exerts a high pressure on the composition.

Preferably, the needless injection device includes a cartridge comprising at least one first chamber containing a first composition that is to be injected.

More preferably, the cartridge comprises a second chamber containing a second composition that is to be injected.

The cartridge may comprise a first chamber intended to receive a first composition that is to be injected, a first injection nozzle communicating with the first chamber and at least one second chamber containing the second composition that is to be injected, a second injection nozzle communicating with the second chamber.

The cartridge may comprise a first chamber intended to receive a first composition that is to be injected, a second chamber containing a second composition that is to be injected, a nozzle that has several outlet ducts and communicating with the first chamber and with the second chamber.

The outlet ducts of the corresponding nozzles may follow the shape of an area that is to be treated, for example a wrinkle.

These cartridges might offer the advantage of being ready for use and of not requiring any setting-up on the part of the user prior to use. It may be specifically, via its geometry and dimensions, dedicated to one particular application. For example, the geometry and the dimensions of the first and second chambers are tailored to the volume and to the nature of the composition that is to be injected, notably the rheology thereof, so as to perform a given treatment. Cartridges may be connected with an interface able to operate both cartridges simultaneously or alternatively. Needleless devices may include a sensor able to assess skin characteristics, such as softness or suppleness. The sensor may be able to adjust the product delivery, in order to get the right dose(s) of composition(s) producing a desired product with a desired viscosity.

The or each chamber may constitute a multi-dose reservoir for the composition that is to be injected. The or each chamber may also contain the composition that is to be injected in a sufficient quantity to carry out a full treatment session involving several injections.

After a dose of the composition contained in a chamber has been injected, this chamber can be refilled automatically, without there being any need to replace the cartridge. That makes it possible to reduce handling operations during treatment.

For preference, notably when the composition is pressurized in a chamber for injection, the supply duct may comprise a shut-off member which is, for example, a ball. The latter may close off the supply duct during injection.

For preference, the shut-off member is kept closed by the pressure in the chamber during injection, and opens between two injections to allow the chamber to fill with the composition.

The cartridge may be supplied to the user with or without the first chamber(s) being pre-fiHed with an individual dose of the composition (s) that is (are) to be injected.

Each chamber may be pressurized in various ways.

For preference, the first chamber houses a first piston connected to a pushrod, the first piston sliding along the longitudinal axis of the first chamber and being driven by the pushrod. The pressure exerted on this first piston during injection is enough to cause the composition to leave the cartridge. This pressure is notably sufficient to cause the composition to at least partially penetrate the skin.

For preference, the injection nozzle forms the distal end of the cartridge. The nozzle comprises at least one outlet duct, the or each outlet duct comprising an opening through which the composition that is to be injected is expelled out.

For preference, the first chamber, the second chamber, the injection nozzle and the supply duct are at least partially defined by a body formed as a single piece. Such a one- piece construction may offer greater strength and prove simpler to manipulate and to use.

The chamber may be tubular in shape. Its wall may converge at its distal end, notably as far as the outlet duct of the injection nozzle.

For preference, the or each second chamber is closed at one of its axial ends by a second piston, notably annular in shape, sliding along the longitudinal axis of the or each second chamber. This second piston may be pushed towards the distal end of the or each second chamber in order to empty same. The pressure may be exerted constantly, by a spring for example, or exerted only during the filling of the first chamber.

In the context of the present invention, what is meant by "viscoelastic or biomechanical properties of the skin" is the extensibility, tonicity, firmness, suppleness and/or elasticity properties of the skin.

What is meant by “cutaneous signs of ageing" is any modifications in the external appearance of the skin due to ageing, whether chronobiologic and/or extrinsic, chiefly photo induced, such as, for example, wrinkles and fine lines, withered skin, flaccid skin, thinned skin, dull skin that lacks radiance, lack of elasticity and/or of tonus of the skin.

As an alternative, the invention is used to prevent, treat and/or reduce a skin-colour disorder. In exemplary embodiments of the invention, the composition is thus a skin colouring composition containing at least one dye.

A further subject of the invention, according to another of the aspects thereof, is a needleless injection system comprising a removable cartridge according to the invention, as defined hereinabove, and a needleless injection device configured to accept the said cartridge.

The cartridge may be designed to be received in a housing of the injection device. As an alternative, the cartridge is configured to be fixed removably, notably by screw-fastening or bayonet fixing, to the injection device. That allows the user to change the cartridge easily to suit his or her needs.

For preference, the injection device comprises a first actuator to act on the pushrod housed in the first chamber of the cartridge.

The device may comprise at least one second actuator, notably of annular shape, to act on the second piston that closes one of the ends of the second chamber.

For preference, the actuators that allow the emptying of the first and second chambers are moved along the longitudinal axis of the device towards the nozzle by drive means such as a source of compressed and/or liquefied gas.

As an alternative, these actuators are moved along the longitudinal axis of the device towards the nozzle by other drive means such as a spring, a motor or an electromagnet.

For preference, the device comprises at least one elastic-return member accompanying or damping the movement of the first piston in the first chamber and/or assisting the latter in returning to its initial position after injection.

The needleless injection system according to the invention may comprise a system for automatic recognition of the treated area, configured to automatically determine the location and depth of the area that is to be treated when the injection system is brought closer to the skin, and to automatically adapt the injection parameters, notably the injection depth. This system may generate information regarding the cartridge to be used and/or regarding the pressure to be applied using the aforementioned drive means, so as to achieve the desired penetration into the skin. The device may provide vibrations, massage, heat or cold, to speed up either an homogeneous blend and/or diffusion and/or reaction of the compositions inside the skin.

According to a second embodiment of the invention, the needless injection system includes at least a container comprising a composition that is to be injected, the container being separated from the device.

The container may be a tube, a bottle, a pot or a case, preferably with a squeezable wall.

The system may comprise at least two compositions to be injected simultaneously or separately into the scalp, or lips.

A further subject of the invention, according to another of its aspects, is a method for the treatment, notably cosmetic, i.e. non- therapeutic, treatment, of human keratin materials, comprising the steps consisting in: - placing a cartridge containing a composition that is to be injected in a needleless injection device so as to form a needleless injection system according to the invention as defined hereinabove,

- bringing the needleless injection system closer to the human keratin materials that are to be treated,

- delivering, upon each injection into the said human keratin materials, a quantity of the composition contained in the cartridge.

The method according to the invention may comprise the step consisting in refilling the first chamber between two injections with a dose of composition taken from the second chamber of the cartridge

The invention notably makes it possible to inject the composition into the epidermis and/or the dermis. In order to influence the depth of injection, it is possible to alter the pressure in the first chamber and the speed at which the composition is ejected from the nozzle towards the skin.

A further subject of the invention, according to another of its aspects, is the cosmetic, i.e. non- therapeutic, use of a needleless injection system according to the invention as defined hereinabove, to improve the appearance, notably the aesthetic appearance, of the skin.

In particular, the needleless injection system according to the invention may be used to prevent, treat and/or reduce a relief and/or a fold in an area of skin, notably a fine line, a wrinkle and/or a scar.

The needless injection device may comprise a unit configured to produce a Venturi effect.

The needless injection device may comprise a piezo electric unit. The device may be provided with a piezoelectric crystal, a triggering member and possibly, a percussion member.

The needless injection device may propel the composition directly through the skin using a pressurized gas unit.

Compositions The composition is preferably a biocompatible cosmetic composition. By "'bio compatible”, it has to be understood a composition capable of fulfilling a specific function with an appropriate response from the skin.

The composition is preferably sterile, and of single use.

The composition may comprise at least one bio-polymer, or solubilized active molecules, or semi soluble molecules or compounds able to react together.

The composition may be a fluid composition containing at least one material in the dispersed state in a Hquid medium, said composition being solidifiable via the reaction of said material into the skin, scalp, or lips. In a variant, the composition is a fluid composition containing at least one material in the dispersed state in another composition containing others compounds, especially bacteria or enzymes.

By “reaction” , it is meant a binding, cross-linking, reticulation, gelification, precipitation, aggregation, association, bounding, mixing, and more generally a transformation of the composition that causes its viscosity to increase between the moment the composition is prepared and some moment after injection, after it has reached its site of destination within the skin, scalp, or lips.

The increase of viscosity may take place under a gelification process or any other physical phenomenon causing particles or molecules of the material of the composition to agglomerate, or reticulate, for example under the effect of electrostatic forces or coalescence, which results in creating some a network, a mesh, an in-skin coating or a layering.

The composition may also generate biological responses, such as collagen fibroblast production but also skin physicho-chemical and mechanical modifications. The composition may generate a feeling of cold or of heat under the skin.

The result of the reaction may generate permanent or semi-permanent results, or reversible or not results. In case of reversible results, the pH of the composition may be modified several times to modify the level of gelification and/or to revert gelification to Hquid.

The reaction is advantageously dedicated to generate an internal network or mesh, continuous or discontinuous, with a minimal thickness and/or volume. Such a network may have a biological and/or mechanical action inside the skin but also on top of skin.

Preferably, the reaction process is triggered by heat, when the temperature of the composition increases over a certain value, which is preferably chosen near to 37°C. The composition may comprise at least one bio-polymer, preferably an alginate or hyaluronic acid, and an ion solution, in particular a divalent ion solution. The viscosity of the bio-polymer increases advantageously into the skin, by polymer gelation, to become solid or semi- solid. Thanks to bio-polymers reaction mechanism and the injection at high quantity and at the right depth into sites which cannot be reached using topical applications, long lasting and visible firming effects are obtained. The composition may include salts, vitamins. The composition may include any other bio compounds to induce or promote the in-skin reaction.

The composition may comprise at least one bio-polymer being able to be modified while in contact with another bio-polymer and/or an alcalin solution or acid solution. The compostion may comprise hydroxyapatite to form a semi-solide complexe polymer with alginate, or other biopolymers

The composition may comprise at least one compound able to crosslink in-situ, swell or become hard or semi-hard when being neutralized by a change of pH, or when adding a source of energy, such light. The composition may comprise at least one compound which is activable by any source of energy, being especially electroactivable and/or photoactivable.

A bio-polymer considered according to the invention may be the alginate Novabel® from Merz, resorbable in 3 to 6 months.

In a preferred embodiment, the composition comprises a sodium alginate and a calcium solution, preferably a CaCC>3 calcium carbonate solution, partially or fully dissolved. The efficient reactivity of alginates with calcium ions has been described in the article of B. Larsen etal “Rheological characterization of an inj ectable alginate gel system” , BMC Biotechnology 2015, pages 15-29. Active compounds solution, such as calcium carbonate solution, allow, by transport of ion energy, generating an in-situ aggregation “egg boxes” forming a film or mesh into skin layers.

Such a sodium alginate is derived from brown sea weeds, and may be a FMC® injectable polymer powder solubilized in water. Such a compound is a hydrophilic colloid, or hydrocolloid, defined as a colloid system in which the colloid particles are hydrophilic polymers dispersed in water.

The reaction may be modulated at will, especially enhanced or delayed, by using at least one buffer and/or sequestrant. Any kind of injectable bio-polymer acceptable for skin injection purposes may be used, as for example the ones allowed by the American Food and Drug Administration (FDA) or the French “Agence nationale de securite du medicament etdes produits de sante” (ANSM).

The viscosity of the composition may range from 1.10 3 Pa s 1 to 10000 Pa s 1 , preferably from 1.10 3 Pa s 1 to 3000 Pa s 1 .

The viscosity is measured at 25 °C and under 1 atm, with a Rheomat 180 viscometer equipped with MK-R-1, 2 or 3 mobile according to the viscosity range and the corresponding measurement cup MB-R-1, 2 or 3 at a rotation speed of 200 min 1 , the measurement being carried out after 10 minutes of rotation (time at which the stabilization of the viscosity and the speed of rotation of the mobile is observed).

The cosmetic composition may be resorbable, that is to say may completely dissolve or assimilated or bio transformed into the skin, in 3 to 6 months, or in 6 to 24 months, which corresponds to slowly resorbable. In a variant, the composition is definitive, non-resorbable.

Preferably, the system a first composition comprising a carbonate solution, and a second composition comprising an alginate.

On the long term, thanks to the invention, the own collagen production of the user may be stimulated thanks to the delivered composition, and long lasting effects can be observed.

Method for preparing an injection

Another object of the invention is a method for preparing an injection of a composition aimed at generating an in-situ reaction into an area of skin, scalp, or lips for correcting a relief or appearance of this area, the injection being performed with the needleless device as defined above, the method comprising:

- performing an acquisition of the topography of the area, preferably an optical acquisition, and

- based on such acquisition of the topography, computing a volume of composition to inject into the skin, scalp, or lips via a needleless injection device.

The computing of the volume of composition to inject may also depend on the depth of injection on the area to treat when successive injections are carried out with displacement of the device relative to the area to be treated from one injection to the other. For example, the device will inject a first quantity of composition when in a first position, then be removed and placed in a second position next to the first one, and then a second quantity of composition is injected, that is different from the first one, because for instance the need of composition locally is less. Accordingly, the device may compute a succession of volumes of composition to inject for respective injection sites.

The computing of the volume of composition to inject may further depend on the properties of reaction of the composition, in particular its viscosity and/or other physical or chemical characteristics after and before reaction.

The position of the device on the skin, scalp, or lips may be automatically detected. The quantity of composition to be locally injected may be controlled as a function of the detected position and of the correction to be applied.

Thanks to the invention, the amount of delivered composition is finely adjusted.

The acquisition of the topography of the area may be performed by a 3D-scan or a profile-meter.

Methods to assess inskin modifications may be used, such as Optical Coherence Tomography (OCT), confocal microscopy, quantitative and qualitative assessment methods. OCT method may be used to monitor and locate injection sites into the skin, by using for example fluorescent molecules, radio tags, specific dosages. OCT method can be useful to follow gel formation inside the skin, scalp, or lips. Confocal microscopy can be useful to follow fluorescent molecules or polymers. The injected volume may be controlled thanks to a scale or a volume measurement device. An OCT portable device may be used. In skin modifications can be done using micro tomography RX

It is also possible to follow the evolution of the injected solution in skin explants by freezing them after injection and performing a mechanical sagittal cut. Bioreactions can be assessed by biomarkers analysis.

Preferably, the composition comprises at least one bio-polymer and an ion solution, the latter being mixed before their injection into the skin, scalp, or lips.

More preferably, the composition comprises at least one bio-polymer and an ion solution, the latter being stored in different containers and separately injected, preferably with a ratio of 50% each.

Method of cosmetic treatment Another object of the invention is a method of cosmetic treatment for correcting a relief or appearance of an area of skin, comprising delivering into the area a composition aimed at generating anin-situ reaction into the skin, scalp, or lips and prepared by the method as defined above.

The depth of injection into the skin advantageously depends on the composition : lighter, finer compositions can be associated with superficial injection whilst heavier, coarser compositions are preferably injected deeper.

The features defined above for the device apply to the methods and vice-versa.

Description of the Drawings

FIG. 3A is an exploded view of injection nozzle, according to an exemplary embodiment of the system according to the invention, and

FIG. 3B is a schematic illustration of injection nozzle of FIG. 3A in a deployed position.

Detailed Description

Optionally, as described above, nozzle 300 includes three separate parts, nozzle base 310, nozzle head 320 and a plunger 330. Nozzle head 320 is attached to injection unit with nozzle interface 340, and plunger 330 is grasped by mechanism 220, so that it can be moved up and down in nozzle head 320. In an exemplary embodiment of the invention, nozzle head 320 comprises an entrance 350, which receives a dose of the composition for injection a cartridge. Optionally, the composition fills up the lower part of nozzle head 320 according to the designated dosage (e.g. up to line 345 that is below entrance 350). Optionally, a pressure hole 355 is positioned on a side of nozzle head 320 above line 345 to allow air to exit when positioning plunger 330 in position for injecting the composition from nozzle head 320.

In an exemplary embodiment of the invention, the composition is ejected from nozzle head 320 via a small hole 325. Optionally, hole 325 is large enough to allow a jet stream of the composition to be ejected through hole 325, but small enough (e.g. less than 0.5 mm) to prevent the composition from dripping out when no pressure is exerted as a result of the viscosity of the composition. Optionally, the size used for hole 325 depends on the type of composition injected, for example for water a diameter between 0.1 mm and 0.3 mm is sufficient. In some embodiments of the invention, nozzle head 320 has multiple holes 325 to form multiple jet streams when injecting the composition. In some embodiments of the invention, nozzle base 310 may be provided with any shaped opening facing downward to be deployed on the skin and causing nozzle head 320 to be positioned at a preset distance from the patient's skin (e.g. between 1 mm to 20 mm).

In an exemplary embodiment of the invention, the internal diameter of nozzle base 310 approximately matches the external diameter of nozzle head 320 so that nozzle head 320 will be held firmly by nozzle base 310. Optionally, the downward opening of nozzle base 310 may be rectangular or square to simplify the process of injecting composition to a larger area of the skin without overlap. Optionally, a user would inject the composition to one position and advance incrementally over the skin until covering the entire larger area with or without overlap. In an exemplary embodiment of the invention, nozzle base 310 has a different height on different sides of its circumference, for example as illustrated side 314 is highest then side 313 then side 312 and then side 311. Optionally, nozzle head 320 comprises a rest protrusion 335, which is positioned to rest on one of the sides (311, 312, 313, and 314) of nozzle base 310 to prevent it from descending deeper into base 310 and getting closer to the skin of the patient. Thus by selecting a side for rest protrusion 335 the user determines the distance between hole 325 and the patient's skin, for example the distance may be set to be between 1 mm to 20 mm or more or less. Optionally, the distance between hole 325 and the patient's skin affects the form of the injection stream that penetrates the patient's skin.

In an exemplary embodiment of the invention, the external layer of the skin 360 is treated by injecting:

- a first composition of sodium alginate into the epidermis layer 360 of the skin,

- a second composition of calcium carbonate into the epidermis layer 360 of the skin.

Optionally, a treatment of the skin can reduce resistance, reduce sensation or prevent contamination.

The injection unit is positioned over the area that needs to be injected. Nozzle base is pressed against epidermis layer 360 causing the dermis layer 365 that is confined by nozzle base 310 to rise up toward nozzle head 320. In an exemplary embodiment of the invention the user of device instructs the injection head to load a dose of composition 1 and composition 2 into nozzle head 320, then the injection head releases mechanism to apply pressure on the composition in nozzle head and inject it in the form of a jet stream toward the epidermis. In an exemplary embodiment of the invention, the jet stream is injected at a pressure between 100 atmospheres to 200 atmospheres, for example 120 atmospheres or 150 atmospheres, so that it will penetrate epidermis 360 and disperse in dermis 365. Optionally, control of the injection pressure determines the depth in the skin into which the injected composition will reach.

The invention is not limited to the examples that have just been described. For example, in one alternative form, the injection device has no first piston for pressurizing the contents of the first chamber.