[go: up one dir, main page]

WO2018033141A1 - 非介入导入方法 - Google Patents

非介入导入方法 Download PDF

Info

Publication number
WO2018033141A1
WO2018033141A1 PCT/CN2017/098037 CN2017098037W WO2018033141A1 WO 2018033141 A1 WO2018033141 A1 WO 2018033141A1 CN 2017098037 W CN2017098037 W CN 2017098037W WO 2018033141 A1 WO2018033141 A1 WO 2018033141A1
Authority
WO
WIPO (PCT)
Prior art keywords
skin
active ingredient
needle
crystal
introduction
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CN2017/098037
Other languages
English (en)
French (fr)
Inventor
王子元
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Priority to US16/323,294 priority Critical patent/US20200188647A1/en
Priority to EP17841113.8A priority patent/EP3501592A4/en
Priority to JP2019507913A priority patent/JP2019528111A/ja
Priority to SG11201900925YA priority patent/SG11201900925YA/en
Priority to BR112019003224A priority patent/BR112019003224A2/pt
Priority to KR1020197004020A priority patent/KR20190042001A/ko
Publication of WO2018033141A1 publication Critical patent/WO2018033141A1/zh
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0021—Intradermal administration, e.g. through microneedle arrays, needleless injectors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/888—Araceae (Arum family), e.g. caladium, calla lily or skunk cabbage
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/361—Carboxylic acids having more than seven carbon atoms in an unbroken chain; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A61K8/65—Collagen; Gelatin; Keratin; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/67—Vitamins
    • A61K8/673—Vitamin B group
    • A61K8/675—Vitamin B3 or vitamin B3 active, e.g. nicotinamide, nicotinic acid, nicotinyl aldehyde
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/67—Vitamins
    • A61K8/676—Ascorbic acid, i.e. vitamin C
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A61K8/735—Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/98—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
    • A61K8/981—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin of mammals or bird
    • A61K8/982—Reproductive organs; Embryos, Eggs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0092—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/87—Application Devices; Containers; Packaging
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M2037/0007—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin having means for enhancing the permeation of substances through the epidermis, e.g. using suction or depression, electric or magnetic fields, sound waves or chemical agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0023—Drug applicators using microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0046—Solid microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0061—Methods for using microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2210/00—Anatomical parts of the body
    • A61M2210/04—Skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2210/00—Anatomical parts of the body
    • A61M2210/06—Head
    • A61M2210/0606—Face

Definitions

  • the present invention relates to the field of transdermal introduction, and more particularly to a non-invasive introduction method. This method can be used in cosmetic and dermal regeneration.
  • the absorption of the active substance by the skin is restricted due to the presence of the stratum corneum of the epidermis; the stratum corneum of the epidermis is a protective barrier formed by the surface layer cells, preventing the high-molecular substances and organic substances from entering the skin and being absorbed by the human body. Because many active substances do not pass through the epidermis into the dermis or deeper into the blood vessels, the effect of regenerating the dermis by applying active substances is poor.
  • interventional percutaneous introduction technique a device with a small needle is used to pierce the epidermis, and the active substance enters the skin through the formed piercing channel.
  • Another form of interventional percutaneous introduction technique is the direct injection of active substance into the dermis.
  • non-invasive percutaneous introduction technique various methods are used to promote the penetration of the active substance into the dermis to a certain extent through the natural passage of the stratum corneum and sweat glands and hair follicles.
  • non-invasive techniques include, but are not limited to, iontophoresis, electrophoresis, electroporation, water jet, air jet, microneedle based, ultrasonic, laser grinding, and other grinding processes.
  • non-invasive percutaneous introduction techniques show that the active substance penetrates deeper into the dermis, it The effect is still not as good as the interventional technique, because the active substance in the non-invasive percutaneous introduction technique needs to penetrate through the stratum corneum, and the stratum corneum has the function of preventing the penetration of the active ingredient.
  • a main object of an embodiment of the present invention is to provide a non-invasive introduction method that greatly improves percutaneous introduction efficiency based on the existing non-invasive percutaneous introduction technique.
  • a non-intrusive import method includes:
  • the acicular crystals form an array of microscopic channels in the epidermal layer, by means of which the active ingredient is introduced into the skin.
  • the applying the needle crystal to the skin comprises:
  • the needle crystals are mixed with the active ingredient and applied to the skin, or
  • the needle crystals are first applied to the skin and the active ingredient is applied to the skin.
  • the method further includes:
  • Such other percutaneous introduction methods include, but are not limited to, iontophoresis, electrophoresis, electroporation, water jet, air jet, microneedle-based, ultrasonic, laser-grinding, and other grinding processes.
  • the method further includes:
  • the method is applied to cosmetic or regenerative techniques.
  • the non-invasive introduction method provided by the embodiment of the invention applies a microscopic structure of needle-like crystals to the face to form an array of microscopic channels, which promotes the penetration of the active substance through the skin barrier and deeply nourishes the skin.
  • the microneedle structure of the crystal will stimulate the vitality of the skin, allowing the skin itself to produce collagen and other substances, and promote skin regeneration.
  • the natural skin treatment of the skin degrades the crystals in the skin and is absorbed by the skin.
  • Figure 1 is a cross-sectional view of a skin structure.
  • FIG. 2 is a finished view of a roller type microneedle or a push type microneedle in the prior art.
  • Fig. 3 is a view showing a comparison between a roller type microneedle and a push type microneedle and the first embodiment of the present application.
  • Fig. 4 is a view showing a comparison between a roller type microneedle and a push type microneedle and the first embodiment of the present application.
  • Figure 5 is a needle crystal suspended in a homogeneous liquid observed under a microscope (100X).
  • Figure 6 is a side view and a cross-sectional view of the needle crystal.
  • Figure 7 is a needle crystal under an optical microscope (10Xx40X).
  • the non-invasive introduction method provided by the present invention adopts a crystal having a microscopic structure of a needle shape, and after the crystal is applied to the skin, the needle crystal forms an array of microscopic channels in the skin layer, by means of the microscopic channel array The active ingredient is introduced into the skin.
  • the microstructure of the crystal is needle-like, invisible to the naked eye, and suspended in a homogeneous liquid.
  • Figure 5 shows the microstructure of the crystal observed under a 100x microscope.
  • the skin layer 1 of the skin is composed of the stratum corneum 11, the transparent layer 12, the granular layer 13, the spinous layer 14, and the base layer 15.
  • the dermis layer 2 of the skin includes tactile bodies 21, capillaries 22, dermal papilla 23, papillary muscles 24 and sebaceous glands 25, and sweat gland passages 33.
  • Skin thickness also varies greatly due to differences in individual age, gender, photoaging, and body parts. Taking facial skin as an example, see Table 1, the facial skin depth (skin 1 and dermis 2) is between 0.5 mm and 1.5 mm. The thickness of the corresponding facial skin 1 is between 0.05 mm and 0.2 mm, and the thickness of the stratum corneum 11 is between 0.015 mm and 0.02 mm; the stratum corneum 11 is the main skin barrier. For the penetration of important active substances, certain means must be used to make the active ingredients easily pass through the stratum corneum.
  • a dense and uniform array of microscopic channels is formed in the skin layer 1 of the skin with a depth of between 0.02 mm and 0.5 mm, preferably further deepening the microscopic channel by means of other means.
  • the array for example, can be between 0.1 mm and 0.8 mm.
  • the microscopic channel array penetrates the stratum corneum 11 which is the main component of the skin barrier, thereby facilitating further penetration of the active ingredient into the dermis layer 2 through the skin barrier. It should be noted that if the introduction method simultaneously uses massage and the like, a microscopic channel array can be formed at a deeper level, that is, the array of crystals can be deepened by the massage method.
  • the crystal after opening up the microscopic channel array, is typically fully absorbed by the body's natural protective mechanisms within 12 to 48 hours, preferably, it can be completely absorbed by the skin within 6 hours to 1 day. No damage to the skin.
  • the specific constitution of the crystal is not specifically limited in the present application. It is possible to use a crystal which can be absorbed by the skin within 2 to 14 days and which has a microscopic structure and which does not cause damage to the skin.
  • Such crystals can be extracted from nature, for example, from plants.
  • a crystal having a needle-like structure capable of eventually degrading and absorbing the skin can also be artificially synthesized. This is not specifically limited.
  • the plant for extraction may preferably be a plant species of the genus Araceae, and the needle-like crystals present in the cultivar are mainly used in plants to give larvae or other organisms that feed on their roots and leaves, causing a certain pain in eating. In order to protect the plant itself, no toxic side effects, it can be the degradation and absorption of organisms.
  • the size of the needle crystal is usually in the order of ⁇ m and nm, for example, the width can be 0.3 ⁇ m. Between 8 ⁇ m, the length can be between 20 ⁇ m and 600 ⁇ m. This may depend on the size of the needle crystals naturally obtained from nature, or the size of the synthetic crystals, which is not limited in this application to be able to enter the skin without causing interventional wounds.
  • the so-called needle shape is only one in a general shape. Any elongated structure that can facilitate access to the skin can be used.
  • a shuttle shape or an arrow shape is preferred.
  • the cross section may be hollow or solid, and the shape of the cross section may be a variety of geometric shapes, such as round, elliptical, etc., round or round shapes, or square, polygonal, triangular, elongated rectangular, etc. Angled shape. Since the longitudinal width of the needle crystal is relatively large, the difference in shape of the cross section has little effect on the ability to enter the skin, but is preferably a circular cross section.
  • the needle crystal may have some specific shapes of the needle crystal are specifically exemplified below.
  • the needle-like crystal structure of the type 1 has a fusiform shape in the middle of the two ends, and has a cross section of a solid square;
  • the needle crystal structure of the type 2 has a top middle convex portion and a rear concave portion as viewed from the longitudinal direction.
  • the shape of the arrow is a hollow diamond with a cross section in the middle;
  • the needle crystal of type 3 has a fusiform shape in the longitudinal direction and a hollow polygon in cross section;
  • the needle crystal structure of type 4 has a fusiform shape in the longitudinal direction, and the upper portion
  • the cross section and the lower cross section are H-shaped, and the middle cross section is a hollow square crystal structure.
  • the needle crystal may have a needle-shaped crystal bundle formed by agglomeration of a plurality of single crystal clusters due to a synthesis process and a natural extraction process, and enter the skin in units of needle-shaped crystal bundles when applied.
  • the active ingredient penetrates the skin mainly by means of osmosis.
  • this effect is small, and most of it is blocked outside the skin barrier, resulting in waste of the active ingredient.
  • the needle crystal opens up the microscopic channel array, and the active ingredient can penetrate the skin barrier through the formed microscopic channel array, thereby promoting the absorption of the active ingredient.
  • Fig. 2 shows a product diagram of a roller type microneedle (left) and a push type microneedle (right) in the prior art.
  • 3 is a schematic view showing the use of a prior art invasive roller type microneedle (for example, a Derma roller type microneedle) and a push type microneedle and a gel preparation of a non-invasive needle crystal of the present application before the skin.
  • Figure 4 shows a schematic view of the three acting on the skin.
  • both the roller type microneedle and the push type microneedle cause trauma to the skin, and since the diameter of the needle in the microneedle method is about the order of millimeters, the distance between each other is also on the order of millimeters, which results in the skin not getting dense care.
  • a push-type microneedle has a large needle size (0.5 mm - 1 mm), and the distance between the needle and the needle is also large (for example, 0.3 mm), resulting in a large skin area between the needle and the needle, which cannot be uniformly covered uniformly.
  • the needle crystal of the present application does not have skin trauma, and due to the microscopic size, it can also form a very dense microscopic channel. It should be noted that in order to display the arrangement of the needle crystals more intuitively, the needle crystals are drawn into a tangible dense arrangement. In fact, these needle crystals need to be observed by means of a microscope, which is invisible to the naked eye. .
  • the appearance of needle-like crystals in the process of penetrating the skin also stimulates the skin's immune system, allowing the skin to produce new collagen and fibers to improve the dermal structure and enhance the toughness and elasticity of the skin.
  • the active ingredient may be applied to the skin after mixing with the needle crystals, or the active ingredient may be applied after the needle crystals are first applied. When mixed with the active ingredient, a homogeneous liquid is obtained. The needle-like microstructure of the crystal is not visible under the naked eye.
  • the type of the active ingredient is not specifically limited in the present application.
  • the active ingredient may be a cosmetic active ingredient or an active ingredient for medical use.
  • the active ingredient for cosmetic use may have a moisturizing, whitening or anti-aging effect.
  • the active ingredient for medical use can be any of the drugs that can be delivered by the transdermal delivery system in the prior art.
  • the methods of the present application can be used alone or in combination with prior art transdermal delivery systems. Achieve better results.
  • the crystal in the dosage form of the product, can be formed into a liquid dosage form or a paste form, a gel dosage form or the like by using a process in the prior art and an active ingredient.
  • the absorption of the needle crystal can be promoted by manual tapping, massage, rolling, pressing, and the like.
  • the absorption of the needle crystal can be further promoted by other percutaneous introduction techniques, such as iontophoresis, electrophoresis, electroporation.
  • Method water jet method, air jet method, microneedle-based device, ultrasonic, laser grinding and other grinding treatments.
  • Both the iontophoresis method and the electrophoresis method act on the charged particles by means of an electric field, thereby introducing the active substance into the skin non-invasively.
  • the action time of the electrophoresis can be usually in the range of 5 minutes to 2, 3 hours, preferably 5 minutes to 60 minutes, further preferably 10 minutes to 30 minutes, further preferably 10 minutes to 20 minutes.
  • the electrophoresis technique of the present invention can rapidly and largely promote the absorption of active ingredients by means of a microscopic channel array opened by needle crystals.
  • Electroporation is a method of cell introduction.
  • the cell membrane of the dermis layer is mainly composed of phospholipid molecules, and the appropriate current can instantaneously open the bilayer spatial structure of the phospholipid molecule and then recover, so that the active material can easily enter when the spatial structure is opened.
  • This method maintains a complete cell membrane and is a good non-invasive method of introducing cells.
  • the introduction method of the present application can exert a synergistic action of absorbing an active substance in combination with an electroporation method.
  • the water jet method uses high-pressure water to impact the skin of the face, so that the effect of the active substance entering the skin through the sweat gland is better, and the thickness of the stratum corneum is also thinned, thereby facilitating the entry of the active substance.
  • the air jet valve is similar to the water jet method in that it uses high-pressure air to act on the surface of the skin to promote the entry of active substances.
  • the ultrasonic method is to place the liquid on the face, and then ultrasonically treat the liquid to generate a slight gas run.
  • the moment of the explosion of the bubble can promote the active ingredient to enter the skin.
  • Laser grinding and other grinding processes are mainly used to thin the stratum corneum and thus further The step promotes the entry of needle crystals and active substances.
  • the non-invasive introduction method provided by the present application can be used in various cosmetic methods.
  • the active ingredient is a pharmaceutical ingredient, it can also be applied to a method of treatment.
  • the present application is directed to providing a non-invasive introduction method that can be applied to various fields that require absorption of substances through the skin.
  • the active ingredient in the above test is a stem cell extract.
  • the TMT device is turned on and set at 80% power.
  • the rolling action acts annularly on the entire facial skin of the subject.
  • the TMT device is turned on and set at 80% power.
  • the rolling action acts on the entire facial skin of the subject in a ring shape.
  • the active ingredient in the above test is a stem cell extract.
  • the TMT device is from Mesoestetic and is a composite functional device for electrophoresis + electroporation.
  • the absorption time of the active ingredient was significantly accelerated in the subjects treated with the needle crystals, about 53.7%, which improved the skin's ability to absorb the active ingredients.
  • Example 2 According to the comparison between Example 1 and Example 2, it was found that the electroconductive technique was used in combination with the needle crystal, and the absorbed active ingredient was more in almost the same time. It can be seen that the use of needle crystals in combination with the introduction methods common in the prior art can achieve a synergistic effect.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Dermatology (AREA)
  • Epidemiology (AREA)
  • Medical Informatics (AREA)
  • Birds (AREA)
  • Hematology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biomedical Technology (AREA)
  • Anesthesiology (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Gerontology & Geriatric Medicine (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Emergency Medicine (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Botany (AREA)
  • Reproductive Health (AREA)
  • Developmental Biology & Embryology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Cosmetics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Media Introduction/Drainage Providing Device (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

提供了非介入导入方法，涉及经皮导入领域，能够促进活性物质为皮肤吸收。非介入导入方法包括：将针状晶体涂覆于皮肤上；针状晶体在表皮层中形成微观通道阵列。可用于活性成分的经皮导入，更常用于美容方法中。

Description

[根据细则37.2由ISA制定的发明名称]　非介入导入方法
本申请要求于2016年8月19日提交中国专利局、申请号为201610698366.X、申请名称为“一种非介入导入方法”的中国专利申请的优先权，其全部内容通过引用结合在本申请中。
技术领域
本发明涉及经皮导入领域，尤其涉及一种非介入导入方法。该方法可用于美容和真皮再生中。
背景技术
随着年龄的增长，由于皮肤所需的重要化合物形成速度变慢，导致皮肤损失胶原蛋白和弹性纤维，使皮肤真皮结构自身功能衰退。若要保持真皮再生处于最佳状态，需要适当的刺激物质及活性物质。
在使用活性物质的情况下，由于表皮角质层的存在，皮肤对活性物质的吸收受到限制；表皮角质层是由表层细胞形成的保护屏障，防止高分子物质和有机物进入皮肤被人体吸收。因为有很多活性物质不能顺利通过表皮进入真皮或者更深进入到达血管，导致通过涂覆活性物质使真皮再生的效果很差。
为了解决该问题，研发了介入式或非介入式经皮导入技术。
介入式经皮导入技术中，使用带小针的装置刺入表皮，使活性物质通过形成的刺入通道进入皮肤。介入式经皮导入技术的另一种形式是直接将活性物质注入真皮中。这些介入技术效果很好，但也给皮肤带来了损伤，若处理不当，会导致并发症。
非介入式经皮导入技术中，采用各种方法促进活性物质通过角质层和汗腺及毛囊的自然通道一定程度地渗透真皮。非介入式技术示例包括但不限于离子导入法、电泳法、电穿孔法、水射流法、空气射流法、微针基装置、超声、激光磨削术和其他磨削处理等。
尽管非介入式经皮导入技术显示活性物质渗透真皮较深，但其 效果仍然没有介入式技术效果好，这是因为非介入式经皮导入技术中活性物质需要通过角质层渗透，而角质层具有阻止活性成分渗透的功能。
申请内容
本发明的实施例的主要目的在于，提供一种非介入导入方法，在现有的非介入式经皮导入技术的基础上大幅度提高经皮导入功效。
为达到上述目的，本发明的实施例采用如下技术方案：
一种非介入导入方法，包括：
将针状晶体涂覆于皮肤上；
所述针状晶体在表皮层中形成微观通道阵列，借助所述微观通道阵列，活性成分导入到皮肤内。
可选的，所述将针状晶体涂覆于皮肤上包括：
将针状晶体与所述活性成分混合后涂覆于皮肤上，或
先将针状晶体涂覆于皮肤上，再将所述活性成分涂覆于皮肤上。
可选的，该方法还包括：
结合其他经皮导入方法促进所述活性成分导入到皮肤内；
所述其他经皮导入方法包括但不限于离子导入法、电泳法、电穿孔法、水射流法、空气射流法、微针基装置、超声、激光磨削术和其他磨削处理。
可选的，该方法还包括：
按压或揉压皮肤以促进活性成分吸收。
可选的，所述方法应用于美容或再生技术中。
本发明实施例提供的非介入导入方法，采用微观结构为针状的晶体涂覆于脸上，形成微观通道阵列，促进活性物质穿透皮肤屏障，深层滋养皮肤。另外透过皮肤后，晶体的微针结构会激发皮肤的活力，让皮肤自身产生胶原蛋白等物质，促进皮肤再生。最后，通过皮肤的自然疗法使皮肤内的晶体变质而被皮肤吸收。
附图说明
为了更清楚地说明本发明实施例或现有技术中的技术方案，下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本发明的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动性的前提下，还可以根据这些附图获得其他的附图。
图1为皮肤结构剖面图。
图2为现有技术中的滚轮式微针或按压式微针的成品图。
图3为滚轮式微针、按压式微针与本申请实施例1作用于皮肤时的对比图。
图4为滚轮式微针、按压式微针与本申请实施例1作用于皮肤后的对比图。
图5为在显微镜(100X)下观测到的悬浮于均质液体中的针状晶体。
图6为针状晶体的侧视图与截面图。
图7为在光学显微镜(10Xx40X)下的针状晶体。
附图标记
1—表皮层      2—真皮层      3—皮下组织
11—角质层     21—触觉小体   31—毛干       36—小动脉
12—透明层     22—毛细血管   32—汗腺孔     37—小静脉
13—颗粒层     23—真皮乳头   33—汗腺管     38—毛乳头
14—有棘层     24—乳头状肌   34—汗腺       39—小体
15—基底层     25—皮脂腺     35—脂肪组织
具体实施方式
下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述。
下面结合附图对本发明实施例提供的非介入导入方法进行描 述。
本发明提供的非介入导入方法，采用一种微观结构为针状的晶体，将该晶体涂覆到皮肤上后，所述针状晶体在表皮层中形成微观通道阵列，借助所述微观通道阵列，活性成分导入到皮肤内。
晶体的微观结构为针状，肉眼不可见，悬浮于均质液体中。图5示出了在100倍显微镜下观测到的晶体的微观结构。
结合图1可知，皮肤的表皮层1由角质层11、透明层12、颗粒层13、有棘层14和基底层15构成。皮肤的真皮层2包括触觉小体21、毛细血管22、真皮乳头23、乳头状肌24和皮脂腺25和汗腺通道33。
由于个人年龄、性别、光老化和身体部分等不同，皮肤厚度(表皮1和真皮2)也有很大变化。以面部皮肤为例，参见表1，面部皮肤深度(表皮1和真皮2)在0.5mm-1.5mm之间。对应的面部表皮1厚度在0.05mm-0.2mm之间，角质层11对应的厚度在0.015mm-0.02mm之间；角质层11为主要的皮肤屏障。对于重要活性物质的渗透，必须采用一定的手段使活性成分很容易地通过角质层。
表1皮肤厚度测量均值
Figure PCTCN2017098037-appb-000001
Figure PCTCN2017098037-appb-000002
针状结构的晶体施加到皮肤后，在皮肤的表皮层1中形成致密均匀的微观通道阵列，深度在0.02mm-0.5mm之间，优选地，在借助其他手段的情况下可进一步加深微观通道阵列，例如可达到0.1mm-0.8mm之间。微观通道阵列透过了皮肤屏障的主要构成——角质层11，从而促进活性成分透过皮肤屏障进一步渗透到真皮层2。需要说明的是，如果本导入方法同时借助按摩等措施，还可以在更深层次形成微观通道阵列，即利用按摩方式可以加深晶体的阵列。
该晶体在开拓了微观通道阵列之后，通常能够在12小时到48小时内被身体的自然防护机制完全吸收，优选的，能够在6小时到1天内被皮肤完全吸收。对皮肤没有任何损伤。
晶体的具体构成在本申请中并不作具体限定。可采用能够在2-14天内为皮肤吸收的、微观结构为针状、并不对皮肤造成损害的晶体。
这种晶体可从自然界中提取，例如可从植物中提取。当然，也可人工合成这种具有针状结构的能够为皮肤最终降解和吸收的晶体。对此，不作具体限定。
所述用于提取的植物优选可为天南星科植物品种，这种品种中存在的针状晶体在植物中主要是用来给予啃食其根茎叶等的小虫或其他生物造成一定地啃食痛感，以起到对植物自身的保护作用，无毒副作用，可为有机体降解和吸收。
针状晶体的尺寸通常在μm和nm级别，例如宽度可在0.3μm 到8μm之间，长度可在20μm到600μm之间。这可取决于从自然界中自然获得的针状晶体的尺寸，或者人工合成的晶体的尺寸，对此本申请不作更多限定，以能够进入皮肤且不造成介入性创伤为宜。
为了更形象的展示针状晶体的微观结构，除了图5中用100X显微示出的位于悬浮液中的针状晶体外，还示出了图7所示的在光学显微镜(10X x 40X)下的提取自刺芋根中的草酸钙针状晶体。
另外，所谓针状形状，仅仅是一个在大体上的形状。任何可以有利于进入皮肤的细长状的结构均可以。例如在纵向上，优选梭状或箭头状。横截面可以是空心的或者实心的，横截面的形状可以是各种各样的几何图形，例如圆形、椭圆形等四周圆滑的形状，或者方形、多边性、三角形、细长类矩形等四周带角度的形状。由于针状晶体的纵宽比较大，横截面的形状差异对于进入皮肤的能力影响不大，但还是以圆形的横截面为优选。
为了更好的说明针状晶体可能具有的微观形状，下面具体举例说明针状晶体的一些具体形状。如图6，类型1的针状晶体结构从纵向上看为两头尖中间粗的梭形，横截面为实心正方形；类型2的针状晶体结构从纵向上看为顶中凸起、末尾凹陷的箭头状，横截面为中间有隔层的中空菱形；类型3的针状晶体从纵向上看为梭形，横截面为中空多边形；类型4的针状晶体结构从纵向上看为梭形，上部横截面及下部横截面为H型，中部横截面为中空方形的晶体结构。
针状晶体除了包括单个的晶体外，还可以由于合成工艺和自然提取工艺，而具有由多个单晶体团簇聚集而形成的针状晶体束，作用时，以针状晶体束为单位进入皮肤。
现有技术中的非介入性导入方法，活性成分主要借助渗透作用而渗透皮肤，然而这种作用是很小的，绝大部分被阻隔在皮肤屏障外，造成活性成分的浪费。通过采用本方法，针状晶体开辟微观通道阵列，则活性成分可以借助形成的微观通道阵列透过皮肤屏障，从而促进了活性成分的吸收。
相比于现有技术中的介入性导入方法，本申请的晶体对皮肤不造成创伤，并且在皮肤表面的均布性要比介入性美容方法中的微针方法改进很多。图2示出了现有技术中的滚轮式微针(左图)和按压式微针(右图)的产品图。图3示出了利用现有技术中的介入式的滚轮式微针(例如Derma滚轮式微针)和按压式微针与本申请的非介入式的针状晶体的凝胶制剂作用于皮肤前的示意图。图4示出了三者作用于皮肤后的示意图。无论是滚轮式微针还是按压式微针都对皮肤造成了创伤，并且由于微针方法中针头的直径大约为毫米级别，彼此间的间距也在毫米级别，这导致皮肤不能得到致密护理。例如按压式微针，针头的尺寸较大(0.5mm—1mm)，针头与针头之间的间距也较大(例如0.3mm)，导致针头与针头之间的皮肤面积较大，不能全面均匀覆盖。而本申请的针状晶体，则不存在对皮肤的创伤，并且由于微观尺寸作用，还能够形成非常致密的微观通道。需要注意的是，为了能够更直观的显示针状晶体的排列，将针状晶体画出为有形的致密排列，实际上，这些针状晶体需要借助显微镜方能观测到，肉眼是无法看到的。
除了促进活性成分吸收外，在穿透皮肤的过程中，针状晶体的出现也刺激了皮肤的免疫系统，使皮肤产生新的胶原蛋白和纤维以改善真皮结构，提升皮肤的韧度弹性。
活性成分既可以与针状晶体一起混合后涂覆于皮肤上，也可以在首先涂覆针状晶体后，再涂覆活性成分。当与活性成分混合后，可得到均质的液体。晶体的针状微观结构在肉眼下并不可见。对于活性成分的种类，本申请并不作具体限定。例如，活性成分可以为美容用活性成分，或者具有医药用途的活性成分。美容用途的活性成分可以为具有保湿、美白或抗衰老等作用。具体的，可以是玻尿酸、胶原蛋白、维生素C、维生素B3、芦荟、熊果苷、亚麻酸、肉毒毒素、肝细胞、羊胎素、人胎素、各种酶等。具有医药用途的活性成分可以任何现有技术中采用经皮递送系统可以传递的药物。本申请的方法可以单独地或者配合现有技术中的经皮递送系统联用， 实现更佳效果。
另外，在产品的剂型上，晶体可以利用现有技术中的工艺与活性成分形成液体剂型或膏状剂型、凝胶剂型等。
将针状晶体施加到皮肤上后，可以通过手动拍打、按摩、揉压、按压等方式促进针状晶体的吸收。
另外，作为本发明的一个优选实施例，在涂覆了针状晶体和活性成分后，还可以借助其他经皮导入技术，进一步促进针状晶体的吸收，例如离子导入法、电泳法、电穿孔法、水射流法、空气射流法、微针基装置、超声、激光磨削术和其他磨削处理等。
离子导入法和电泳法均借助于电场作用，电场作用于带电粒子，从而将活性物质非介入地导入皮肤内。
电泳的作用时间通常可在5分钟到2、3小时的范围内，优选5分钟到60分钟，进一步优选，10分钟到30分钟，进一步优选10分钟到20分钟。相比于现有技术中单纯采用电泳技术，本发明的电泳技术可以借助针状晶体开辟的微观通道阵列，迅速和大量地促进活性成分的吸收。
电穿孔是一种细胞导入方法。真皮层的细胞膜主要由磷脂分子组成，适当的电流可以瞬时打开磷脂分子的双分子层空间结构，然后恢复，使得活性物质在空间结构打开时容易进入。这种方法保持完整的细胞膜，是一种良好的非介入式导入细胞方法。本申请的导入方法配合电穿孔法能够发挥吸收活性物质的协同作用。
水射流法，采用高压水冲击脸部皮肤，使得活性物质通过汗腺进入皮肤内的效果更佳，同时也能使得角质层的厚度变薄，从而更利于活性物质进入。
空气射流阀，原理类似于水射流法，采用高压空气作用于皮肤表面，对活性物质起到推动进入的作用。
超声法是将液体置于脸部，然后超声处理，使液体产生微小气跑，气泡的爆破的瞬间可起到推动活性成分进入皮肤的作用。
激光磨削术和其他磨削处理主要用于使角质层变薄，从而进一 步促进针状晶体及活性物质的进入。
上述这些方法均可以在施加针状晶体和/或活性成分时同时使用，从而起到联合的协同作用。
根据上述本申请的作用原理，本申请提供的非介入导入方法可以用于各类美容方法中。可选的，如果活性成分为医药成分，还可以应用于治疗方法中。总之，本申请致力于提供一种非介入导入方法，可应用于各个需要透过皮肤促进物质吸收的领域。
为了更好的说明本申请提供的非介入导入方法，下面以具体实施例进行说明。
实施例1
1、使用清洁乳和清洁凝胶清洁受试者面部的化妆品、油脂、尘土。
2、将活性成分施加到受试者面部，施加多次，每次1ml，具体如下：
a.将1ml活性成分施加到面部皮肤上，并使其均匀完全覆盖于面部皮肤上。
b.当面部皮肤上的活性成分经吸收及蒸发变干时，再次将1ml活性成分施加到面部皮肤上，并使其均匀完全覆盖于面部皮肤上。
c.重复步骤a和b，直到总共5ml的活性成分用完。
d.记录从开始施加到施加结束的总时间。
对比例1
受试者在接受实施例1中处理后第五天，接受对比例1的处理。以防止前次试验对后次试验的干扰，并保证实施例1与对比例1的皮肤状况最为接近。
1、使用清洁乳和清洁凝胶清洁受试者面部的化妆品、油脂、尘土。
2、将1ml的针状晶体施加到脸部，并有力按摩1分钟。
3、将活性成分施加到受试者面部，施加多次，每次1ml，具体 如下：
a.将1ml活性成分施加到面部皮肤上，并使其均匀完全覆盖于面部皮肤上。
b.当面部皮肤上的活性成分经吸收及蒸发变干时，再次将1ml活性成分施加到面部皮肤上，并使其均匀完全覆盖于面部皮肤上。
c.重复步骤a和b，直到总共5ml的活性成分用完。
d.记录从开始施加到施加结束的总时间。
注：上述试验中的活性成分为干细胞提取物。
将五名受试者用尽全部活性成分所需要的总时间列于表2中。
表2活性成分的吸收时间
Figure PCTCN2017098037-appb-000003
从表2可以看出，使用针状晶体处理的受试者对于活性成分的吸收时间明显加快，约35.2％，改善了皮肤对于活性成分的吸收能力。
实施例2
1、使用清洁乳和清洁凝胶清洁受试者面部的化妆品、油脂、尘土。
2、将含有20ml活性成分的试剂瓶连接到TMT装置的滚头上。
3、TMT装置打开，并设置在80％功率。
4、滚动作用器以环状作用于受试者的整个面部皮肤。
5、记录从开始施加到活性成分完全能用完的时间。
对比例2
受试者在接受实施例2中处理后第五天，接受对比例2的处理。以防止前次试验对后次试验的干扰，并保证实施例2与对比例2的皮肤状况最为接近。
1、使用清洁乳和清洁凝胶清洁受试者面部的化妆品、油脂、尘土。
2、将2ml的针状晶体施加到脸部，并有力按摩1分钟。
3、将含有20ml活性成分的试剂瓶连接到TMT装置的滚动作用器上。
4、TMT装置打开，并设置在80％功率。
5、滚动作用器以环状作用于受试者的整个面部皮肤。
6、记录从开始施加到活性成分完全能用完的时间。
注：上述试验中的活性成分为干细胞提取物。TMT装置来自于美斯蒂克(Mesoestetic)，为一种电泳+电穿孔的复合功能装置。
将五名受试者的面部皮肤用尽全部活性成分所需要的总时间列于表3中。
表3活性成分的吸收时间
Figure PCTCN2017098037-appb-000004
从表3可以看出，使用针状晶体处理的受试者对于活性成分的吸收时间明显加快，约53.7％，改善了皮肤对于活性成分的吸收能力。
并且根据实施例1和实施例2的对比发现，采用电导技术配合针状晶体，在几乎相同的时间内，所吸收的活性成分更多。可见，采用针状晶体配合现有技术中常见的导入方法，能够起到协同效果。
以上所述，仅为本发明的具体实施方式，但本发明的保护范围并不局限于此，任何熟悉本技术领域的技术人员在本发明揭露的技术范围内，可轻易想到变化或替换，都应涵盖在本发明的保护范围之内。因此，本发明的保护范围应以所述权利要求的保护范围为准。

Claims (6)

  1. 一种非介入导入方法，其特征在于，包括：
    将针状晶体涂覆于皮肤上；
    所述针状晶体在表皮层中形成微观通道阵列，借助所述微观通道阵列，活性成分导入到皮肤内。
  2. 根据权利要求1所述的非介入导入方法，其特征在于，所述将针状晶体涂覆于皮肤上包括：
    将针状晶体与所述活性成分混合后涂覆于皮肤上。
  3. 根据权利要求1所述的非介入导入方法，其特征在于，所述将针状晶体涂覆于皮肤上包括：
    先将针状晶体涂覆于皮肤上，再将活性成分涂覆于皮肤上。
  4. 根据权利要求1-3任一项所述的非介入导入方法，其特征在于，还包括：结合其他经皮导入方法促进所述活性成分导入到皮肤内；
    所述其他经皮导入方法包括但不限于离子导入法、电泳法、电穿孔法、水射流法、空气射流法、微针基装置、超声、激光磨削术和其他磨削处理。
  5. 根据权利要求1-3任一项所述的非介入导入方法，其特征在于，还包括：
    按压或揉压皮肤以促进活性成分吸收。
  6. 根据权利要求1所述的非介入导入方法，其特征在于，所述方法应用于美容方法中。
PCT/CN2017/098037 2016-08-19 2017-08-18 非介入导入方法 Ceased WO2018033141A1 (zh)

Priority Applications (6)

Application Number Priority Date Filing Date Title
US16/323,294 US20200188647A1 (en) 2016-08-19 2017-08-18 Non-invasive transportation method
EP17841113.8A EP3501592A4 (en) 2016-08-19 2017-08-18 NON-INVASIVE RELEASE PROCEDURE
JP2019507913A JP2019528111A (ja) 2016-08-19 2017-08-18 非侵襲的輸送法
SG11201900925YA SG11201900925YA (en) 2016-08-19 2017-08-18 Non-invasive transportation method
BR112019003224A BR112019003224A2 (pt) 2016-08-19 2017-08-18 método de transporte não invasivo
KR1020197004020A KR20190042001A (ko) 2016-08-19 2017-08-18 비침습적 수송 방법

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201610698366.X 2016-08-19
CN201610698366.XA CN106166326A (zh) 2016-08-19 2016-08-19 一种非介入导入方法

Publications (1)

Publication Number Publication Date
WO2018033141A1 true WO2018033141A1 (zh) 2018-02-22

Family

ID=57376568

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2017/098037 Ceased WO2018033141A1 (zh) 2016-08-19 2017-08-18 非介入导入方法

Country Status (8)

Country Link
US (1) US20200188647A1 (zh)
EP (1) EP3501592A4 (zh)
JP (1) JP2019528111A (zh)
KR (1) KR20190042001A (zh)
CN (2) CN114129886A (zh)
BR (1) BR112019003224A2 (zh)
SG (1) SG11201900925YA (zh)
WO (1) WO2018033141A1 (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019231401A1 (en) * 2018-05-30 2019-12-05 Tze Guan Ong Non-invasive transportation method

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114129886A (zh) * 2016-08-19 2022-03-04 王子元 一种非介入导入方法
CN112494796A (zh) * 2020-12-02 2021-03-16 中山大学 一种拍打式微针美容贴片

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090011026A1 (en) * 2005-08-24 2009-01-08 Marc Egen Transcorneal system for delivery of a pharmaceutical agent
CN101626775A (zh) * 2006-10-05 2010-01-13 玛丽亚·维拉尼 Spongilla骨针作为皮肤磨平术设备或表面重建物理疗法的用途
CN103142479A (zh) * 2013-03-29 2013-06-12 中国药科大学 一种磷脂-维生素e琥珀酸聚乙二醇酯胶束的应用
CN105616187A (zh) * 2016-02-04 2016-06-01 上海新肌生物科技有限公司 一种直达真皮层的涂抹式水光针及其制备方法
CN105999535A (zh) * 2016-04-27 2016-10-12 厦门大学 海绵骨针作为皮肤物理促渗剂的应用
CN106166326A (zh) * 2016-08-19 2016-11-30 王子元 一种非介入导入方法

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2787320B1 (fr) * 1998-12-17 2002-11-29 Veronique Simon Nouvelle methode de peeling et preparations pour la mise en oeuvre de cette methode
AU2003278775B2 (en) * 2002-07-01 2010-06-17 Maria Villani Porifera-based therapeutic compositions for treating and preventing skin diseases
WO2013188926A1 (en) * 2012-06-22 2013-12-27 The University Of Queensland Method and composition for delivering a compound through a biological barrier
KR101760045B1 (ko) * 2014-04-08 2017-07-20 (주)파이온텍 해면에서 얻은 천연 바이오 스폰지로부터 미세침의 정제 및 추출 방법

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090011026A1 (en) * 2005-08-24 2009-01-08 Marc Egen Transcorneal system for delivery of a pharmaceutical agent
CN101626775A (zh) * 2006-10-05 2010-01-13 玛丽亚·维拉尼 Spongilla骨针作为皮肤磨平术设备或表面重建物理疗法的用途
CN103142479A (zh) * 2013-03-29 2013-06-12 中国药科大学 一种磷脂-维生素e琥珀酸聚乙二醇酯胶束的应用
CN105616187A (zh) * 2016-02-04 2016-06-01 上海新肌生物科技有限公司 一种直达真皮层的涂抹式水光针及其制备方法
CN105999535A (zh) * 2016-04-27 2016-10-12 厦门大学 海绵骨针作为皮肤物理促渗剂的应用
CN106166326A (zh) * 2016-08-19 2016-11-30 王子元 一种非介入导入方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP3501592A4 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019231401A1 (en) * 2018-05-30 2019-12-05 Tze Guan Ong Non-invasive transportation method
EP3801733A4 (en) * 2018-05-30 2022-07-13 Tze Guan Ong NON-INVASIVE TRANSPORTATION METHOD

Also Published As

Publication number Publication date
US20200188647A1 (en) 2020-06-18
JP2019528111A (ja) 2019-10-10
CN114129886A (zh) 2022-03-04
CN106166326A (zh) 2016-11-30
EP3501592A1 (en) 2019-06-26
EP3501592A4 (en) 2020-06-03
KR20190042001A (ko) 2019-04-23
BR112019003224A2 (pt) 2019-07-16
SG11201900925YA (en) 2019-03-28

Similar Documents

Publication Publication Date Title
Arora et al. Automated microneedling device-a new tool in dermatologist's kit-a review.
US20220226206A1 (en) Cosmetic appearance of skin
US10555896B2 (en) Skin penetration enhancing method and its penetration enhancer
Sasaki Micro-needling depth penetration, presence of pigment particles, and fluorescein-stained platelets: clinical usage for aesthetic concerns
KR20160135792A (ko) 조합된 음파 및 이온영동 스킨 케어 디바이스
Majid et al. Microneedling and its applications in dermatology
CN104826228B (zh) 用于皮肤修复与保养的生物贴
HUE031064T2 (en) A method of skin skin cosmetic treatment by using NGF-containing compositions
WO2018033141A1 (zh) 非介入导入方法
KR102120245B1 (ko) 눈썹 발모 시술 방법
CN206120721U (zh) 无痛揿针
CN206120722U (zh) 无痛揿针电化学贴膏
US20210085945A1 (en) Non-invasive Transportation Method
US20160135889A1 (en) Method for depilation by photothermolysis with melanin
CN206120723U (zh) 足疗手疗的无痛揿针
CN206120724U (zh) 针加灸暖贴式无痛揿针
RU2197952C1 (ru) Способ омоложения кожи (варианты)
CN206228604U (zh) 透皮贴式可排湿排毒的无痛揿针
Elghblawi Medical micro-needling
CN106074153A (zh) 无痛揿针电化学贴膏
CN206252660U (zh) 护肤膜式美容保健无痛揿针
Sharma et al. Drug Diffusion through Nails/an Update Review
Sahoo et al. Transungual drug delivery system a review
CN112274479A (zh) 一种基于毛母干细胞和微针的生发方法
CN113262391A (zh) 紧致皮肤微针贴

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 17841113

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2019507913

Country of ref document: JP

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 20197004020

Country of ref document: KR

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

REG Reference to national code

Ref country code: BR

Ref legal event code: B01A

Ref document number: 112019003224

Country of ref document: BR

ENP Entry into the national phase

Ref document number: 2017841113

Country of ref document: EP

Effective date: 20190319

ENP Entry into the national phase

Ref document number: 112019003224

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20190218

WWW Wipo information: withdrawn in national office

Ref document number: 2017841113

Country of ref document: EP