CN117883691A - Composite micro-eye patch and preparation method and application thereof - Google Patents
Composite micro-eye patch and preparation method and application thereof Download PDFInfo
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- CN117883691A CN117883691A CN202410036070.6A CN202410036070A CN117883691A CN 117883691 A CN117883691 A CN 117883691A CN 202410036070 A CN202410036070 A CN 202410036070A CN 117883691 A CN117883691 A CN 117883691A
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- hyaluronic acid
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Classifications
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- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/0204—Specific forms not provided for by any of groups A61K8/0208 - A61K8/14
-
- 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
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/005—Preparations for sensitive skin
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- 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
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- 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
- A61K2800/91—Injection
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- 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
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- 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
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- 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
- A61M2037/0053—Methods for producing microneedles
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- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Engineering & Computer Science (AREA)
- Gerontology & Geriatric Medicine (AREA)
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- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a composite micro-eye patch for eye skin care and a preparation method and application thereof. The compound micro-eye patch is crescent-shaped and is made of a micro-needle array, and each micro-needle comprises a needle point part and a substrate part. The needle tip part is made of small molecule hyaluronic acid with the molecular weight of 1-100 ten thousand; the substrate part is made of a mixture of macromolecular hyaluronic acid and micromolecular hyaluronic acid with the molecular weight of 20-200 ten thousand, and the mass ratio of the macromolecular hyaluronic acid to the micromolecular hyaluronic acid is 1:1-1:100. The invention adopts the mechanical stimulation of the micro needle and the synergistic action of high and low molecular weight hyaluronic acid, has double functions of internal repair and external maintenance, improves the self-repair capability of the skin, and further enhances the youthful capability of the eye skin after treatment.
Description
Technical Field
The invention belongs to the field of medical cosmetology, and particularly relates to a composite micro-eye patch and a preparation method and application thereof.
Background
Skin aging is a complex process involving a variety of factors and mechanisms. With age, the physiological structure of the skin changes, with loss of collagen and elastin being one of the most predominant changes. These two proteins are key components that impart elasticity and support to the skin, and their loss causes the skin to lose its firmness and elasticity, and to develop wrinkles and sagging. Meanwhile, aging also causes the skin surface stratum corneum to be thickened, and the number of blood vessels and capillaries of the dermis is reduced, so that the skin is more easily damaged and drier. Sebaceous gland hypofunction is also part of the aging process, leading to loss of skin moisture, further exacerbating the appearance of dryness and wrinkles. External environmental factors such as ultraviolet radiation, pollutants, environmental stress, and bad lifestyle (smoking, excessive drinking, etc.) also play an important role in skin aging.
Hyaluronic acid is a polysaccharide, a linear molecular structure consisting of N-acetylglucosamine and glucuronic acid monomers. It is unique in that it can form a network structure in skin and soft tissues, and maintain the hydration state and elasticity of the tissues by absorbing and retaining water molecules. Hyaluronic acid can be classified into a high molecular weight and a low molecular weight according to the molecular weight thereof. High molecular weight hyaluronic acid is commonly used to moisturize and increase skin elasticity. It can form protective film on skin surface to hold water and make skin moist, and has certain functions of resisting oxidation and protecting skin barrier. The hyaluronic acid with low molecular weight has smaller molecules, is easier to be absorbed by skin, can penetrate into the skin, and has better permeability. It is often used in skin care products to help increase skin elasticity, reduce fine lines and wrinkles, and repair damaged tissue, promoting wound healing. Hyaluronic acid is widely used in the cosmetic field in the form of gels for smoothing fine lines, wrinkles on the skin surface, or enhancing facial contours, making facial lines younger and richer. In skin care products, the use of hyaluronic acid aims at improving skin moisturization, elasticity and gloss, reducing wrinkles and fine lines. In addition, hyaluronic acid is used in the medical field for treating diseases such as arthritis, relieving pain by joint injection and enhancing joint lubrication, and is used as an intraocular filler for promoting the healing process of eyes in ophthalmic surgery.
The micro-needle transdermal drug delivery technology is an innovative drug delivery method, and micro-stimulation is formed on the skin surface through the micro-needle, so that drug absorption is promoted, and the treatment effect is improved. Compared with the traditional treatment method, the microneedle transdermal drug delivery technology has a plurality of advantages: firstly, the microneedle can break the barrier of the skin stratum corneum, enhance the skin permeability of the medicine and improve the curative effect. Secondly, the dosage of the medicine is reduced, the side effect is reduced, and the medicine is directly delivered to the target skin site. The technical design is convenient for the patient to use, and does not need to be operated by a professional doctor. The microneedle is made of degradable materials, the microneedle body is gradually degraded, no extra damage is caused to the skin, and no pain is felt. The microneedle transdermal drug delivery technology is widely applied to the fields of drug delivery, wound healing, vaccination, tissue fluid extraction, biomarker detection and the like. Among them, the development of soluble microneedles has made a breakthrough progress in recent years. Microneedle transdermal delivery technology is considered an important drug delivery method, bringing more promise for clinical treatment.
However, there are few reports of the use of microneedle transdermal technology for ocular skin care.
Disclosure of Invention
The invention aims to provide a composite micro-eye patch for caring eye skin and a preparation method thereof. The compound micro-eye patch is made of hyaluronic acid with high and low molecular weight, can effectively penetrate through skin barrier, and can be used for treating and repairing problems of eye skin aging, collagen loss and the like caused by aging or diseases.
The compound micro-eye patch for eye skin care provided by the invention is crescent-shaped and is made of a micro-needle array, a single micro-needle comprises a needle point part and a substrate part,
the length of the composite micro-eye patch is 20-150mm, the width of the composite micro-eye patch is 15-40mm, and the number of micro-needles of the single micro-eye patch is 200-2000; the single microneedle is conical, the diameter of the bottom surface of the cone is 100-600mm, and the height is 200-1000mm; the distance between the tip of the micro needle is 300-800mm;
wherein the needle tip part is made of small molecule hyaluronic acid, and the molecular weight of the small molecule hyaluronic acid is 1-100 ten thousand;
the substrate part is made of a mixture of macromolecular hyaluronic acid and small-molecular hyaluronic acid, the molecular weight of the small-molecular hyaluronic acid is 1-100 ten thousand, the molecular weight of the macromolecular hyaluronic acid is 20-200 ten thousand, and the mass ratio of the macromolecular hyaluronic acid to the small-molecular hyaluronic acid can be 1:1-1:100.
The composite micro-eye patch for caring eye skin is prepared by a method comprising the following steps:
1) Preparing small molecular hyaluronic acid into small molecular hyaluronic acid aqueous solution, and filling the small molecular hyaluronic acid aqueous solution into a cavity of a needle point part of the die;
2) Preparing macromolecule hyaluronic acid and micromolecule hyaluronic acid into macromolecule hyaluronic acid aqueous solution and micromolecule hyaluronic acid aqueous solution respectively, mixing the large-component hyaluronic acid aqueous solution and the micromolecule hyaluronic acid aqueous solution, and filling the mixture into a cavity of a substrate part of a die;
3) Drying and demolding the mold;
4) And covering the substrate part with a viscous material to obtain the composite micro-eye patch.
In the step 1) of the method, the molecular weight of the small molecule hyaluronic acid is 1-100 ten thousand;
the concentration of the small molecule hyaluronic acid aqueous solution is 5-150mg/mL;
in the step 2), the molecular weight of the macromolecular hyaluronic acid is 20-200 ten thousand, and the concentration of the macromolecular hyaluronic acid aqueous solution is 1-40mg/mL;
the molecular weight of the small molecule hyaluronic acid is 1-100 ten thousand; the concentration of the small molecule hyaluronic acid aqueous solution is 5-150mg/mL;
in the preparation method, the concentration of the solution of the macromolecular hyaluronic acid and the solution of the small molecular weight hyaluronic acid has obvious influence on the preparation process smoothly, the concentration is too high, the solution is difficult to enter the needle point, the substrate has fine bubbles, the solution is added for many times when the concentration is too low, the flow is more complex, and the operation is more complicated.
The macromolecular hyaluronic acid aqueous solution and the micromolecular hyaluronic acid aqueous solution are mixed according to the volume ratio of 1:1-1:100.
The liquid adding amount of the macromolecular hyaluronic acid and the micromolecular hyaluronic acid in the preparation process has obvious influence on the flexibility of the obtained micro-eye patch.
The application of the composite micro-eye patch in preparing a product for caring eye skin also belongs to the protection scope of the invention.
The product for caring eye skin can be used for treating and repairing eye skin aging and collagen loss caused by aging or diseases.
According to the invention, the flexible patch is manufactured on the premise of ensuring the mechanical property and the normal efficacy of the needle tip by adjusting the material dosage and the proportion, and the flexible patch can be perfectly attached and quickly dissolved when being used on the skin of eyes, so that the problem of non-attachment to the skin caused by hardness is avoided.
The invention adopts the mechanical stimulation of the micro needle and the synergistic action of high and low molecular weight hyaluronic acid, has double functions of internal repair and external maintenance, improves the self-repair capability of the skin, and further enhances the youthful capability of the eye skin after treatment.
The hyaluronic acid microneedle system, the hyaluronic acid microneedle method and the application are only applied to the field of eye mask, wherein the hyaluronic acid microneedle is designed, prepared and used for releasing hyaluronic acid in eyes or skin areas around eyes so as to achieve the purpose related to eye care
Drawings
FIG. 1 is a side view of a flexible crescent-shaped micro-eye patch made in accordance with the present invention.
Fig. 2 is a side view of a microneedle array of a flexible crescent-shaped micro-eye patch of the present invention taken using an optical microscope.
Fig. 3 is a microneedle array image of a flexible crescent-shaped micro-eye patch made according to the present invention taken using a Scanning Electron Microscope (SEM).
Fig. 4 is a single microneedle image of a flexible crescent-shaped micro-eye patch made according to the present invention taken using a Scanning Electron Microscope (SEM).
Fig. 5 is a graph showing the change in the mechanical force-displacement relationship that the tip of the microneedle can withstand in the micropin of example 2 of the present invention.
Fig. 6 is an image of the micro-eye patch of example 3 of the present invention applied to in vitro pigskin puncture.
Fig. 7 is a photograph showing various time points of the skin wound healing test of the mouse in example 4 of the present invention.
Fig. 8 is a superimposed image of wound area at various time points in example 4 of the present invention.
Fig. 9 is a graph showing the percentage of skin wound area of mice at various time points in example 4 of the present invention.
Detailed Description
The following detailed description of the invention is provided in connection with the accompanying drawings that are presented to illustrate the invention and not to limit the scope thereof. The examples provided below are intended as guidelines for further modifications by one of ordinary skill in the art and are not to be construed as limiting the invention in any way.
The experimental methods in the following examples, unless otherwise specified, are conventional methods, and are carried out according to techniques or conditions described in the literature in the field or according to the product specifications. Materials, reagents and the like used in the examples described below are commercially available unless otherwise specified.
Example 1 preparation of a Flexible crescent micro-eye Patch
First, the mold was thoroughly cleaned using an ultrasonic cleaner for 3 hours and periodically replaced with sterile deionized water during the process. After the cleaning is completed, the mold is dried. 70 milligram of small molecule hyaluronic acid with molecular weight of 10 to 20 ten thousand is dissolved in 1 milliliter of sterile deionized water for complete mixing to prepare a solution with concentration of 70 milligrams/milliliter of small molecule hyaluronic acid. After being sufficiently dissolved by a magnetic stirrer, 400. Mu.L of the prepared solution was poured into a mold using a pipette. The solution was ensured to fully fill the mold cavity by vacuum negative pressure de-bubbling, the valve was closed for about 15 seconds each time, then the vent was opened, and this step was repeated 3 times. The larger bubbles were then removed with a pipette until the solution completely entered the tip. Meanwhile, 20 milligram of hyaluronic acid with molecular weight of 55 to 70 ten thousand and 1 milliliter of sterile deionized water are taken, and macromolecule water-soluble hyaluronic acid solution with concentration of 20 milligrams/milliliter is obtained according to the same solution preparation mode. Fully mixing the glass fiber reinforced plastic material with the prepared 70 mg/ml small molecule water-soluble hyaluronic acid solution according to the volume ratio of 1:4, taking 1.2 ml, and adding the mixture into a die to ensure that the solution fully fills the substrate. And (5) putting the die into a constant-temperature drying oven for drying, and then demolding. The microneedle substrate was covered with 3M glue to make a crescent microneedle patch. The obtained microneedle patch has a length of 46.61 mm, a width of 18.09 mm, a diameter of 280 micrometers at the bottom of each microneedle, a height of 650 micrometers, a needle tip spacing of 800 micrometers, and a crescent moon shape with about 1000 individual microneedles.
Fig. 1 shows a side view of the resulting crescent patch, highlighting its excellent flexibility, being able to perfectly follow the skin surface, with extremely high practical value.
Fig. 2 and fig. 3 and 4 are photographs showing specific morphology of the microneedle, which are taken using an optical microscope and a scanning electron microscope, respectively, showing the detailed structure of the microneedle.
Example 2 mechanical Property test of microneedles
The mechanical stress experienced by the microneedle patch on the horizontal platform was tested by a texture analyzer. The microneedle tips were pressed up vertically at a rate of 0.1mm/s and the compressive force was recorded and stopped when the tip deformation reached 90%.
Fig. 5 shows the mechanical force and displacement experienced by each microneedle as a function of time. The microneedle was judged to be able to successfully penetrate the skin based on the 0.045N mechanical force required for transdermal penetration.
Example 3 in vitro skin penetration test
Full thickness pigskin was used to evaluate the penetration ability of the microneedle patch into the skin. Pig skin was fixed to the bottom of the dish, the skin was penetrated quickly with a microneedle, and pressure was applied for 5 minutes. Figure 6 shows a comparison of the effect of the microneedle before and after application to pigskin in an in vitro experiment.
Example 4, skin wound healing test in mice
Balb/c female mice of eight weeks of age were selected, back hair was removed, and exposed skin was disinfected. Subsequently, a full-thickness skin injury model was made using a disposable 8mm skin perforator, and the mice were randomly divided into three groups, a control group (untreated), a commercially available healing-promoting gel group (coated with a commercially available recombinant bovine basic fibroblast growth factor gel), and a microneedle group. And square micro-needle eye film patches were prepared according to the concentrations and methods described in example 1. After molding, at designated time intervals (days 1, 3, 5, 7, 10, 14), a wound image was acquired and then dressing was changed, with the microneedle patch completely covering the wound area and secured with a bandage. The obtained wound surface Image was evaluated using Image J software. The skin defect area and the inner diameter were measured at each time point after the microneedle was peeled off from the wound surface. The percent skin defect area on days 1, 3, 5, 7, 10 and 14 was calculated using the skin defect area on day 1 as a control (100%).
The photographs of the experimental results of the animal model are shown in fig. 7, and the wound areas after the microneedle treatment at the same time point are smaller than those of the control group.
Wound superposition at various time points as shown in fig. 8, it can be seen that the microneedle array wound area is significantly reduced.
The skin wound area percentage results are shown in fig. 9, and it can be seen that the microneedle group exhibited the most remarkable therapeutic effect.
Wound healing and ocular skin care both involve repair and protection of skin tissue. Even minor injuries such as skin aging and minor trauma around the eyes require repair and protection procedures for the skin tissue. Skin is the largest organ of the body, one of its main functions being to provide barrier protection. The skin around the eyes is similar to the skin of other body parts, and it is also necessary to maintain a barrier function, prevent external irritants from entering the area around the eyes, and at the same time prevent water loss and keep moist. The health of the skin around the eyes is critical to the overall health of the eyes. Thus, maintaining healthy and good healing of the skin in this area can reduce injury and infection of the eye from the external environment.
The present invention is described in detail above. It will be apparent to those skilled in the art that the present invention can be practiced in a wide range of equivalent parameters, concentrations, and conditions without departing from the spirit and scope of the invention and without undue experimentation. While the invention has been described with respect to specific embodiments, it will be appreciated that the invention may be further modified. In general, this application is intended to cover any variations, uses, or adaptations of the invention following, in general, the principles of the invention and including such departures from the present disclosure as come within known or customary practice within the art to which the invention pertains.
Claims (7)
1. The compound micro-eye patch is crescent-shaped and is made of a micro-needle array, wherein a single micro-needle comprises a needle point part and a substrate part,
the length of the composite micro-eye patch is 20-150mm, the width of the composite micro-eye patch is 15-40mm, and the number of micro-needles of the single micro-eye patch is 200-2000; the single microneedle is conical, the diameter of the bottom surface of the cone is 100-600mm, and the height is 200-1000mm; the distance between the tip of the micro needle is 300-800mm;
wherein the needle tip part is made of small molecule hyaluronic acid, and the molecular weight of the small molecule hyaluronic acid is 1-100 ten thousand;
the substrate part is made of a mixture of macromolecular hyaluronic acid and small-molecular hyaluronic acid, the molecular weight of the small-molecular hyaluronic acid is 1-100 ten thousand, the molecular weight of the macromolecular hyaluronic acid is 20-200 ten thousand, and the mass ratio of the macromolecular hyaluronic acid to the small-molecular hyaluronic acid is 1:1-1:100.
2. A method of making the composite micro-eye patch of claim 1, comprising the steps of: 1) Preparing small molecular hyaluronic acid into small molecular hyaluronic acid aqueous solution, and filling the small molecular hyaluronic acid aqueous solution into a cavity of a needle point part of the die;
2) Preparing macromolecule hyaluronic acid and micromolecule hyaluronic acid into macromolecule hyaluronic acid aqueous solution and micromolecule hyaluronic acid aqueous solution respectively, mixing the large-component hyaluronic acid aqueous solution and the micromolecule hyaluronic acid aqueous solution, and filling the mixture into a cavity of a substrate part of a die;
3) Drying and demolding the mold;
4) And covering the substrate part with a viscous material to obtain the composite micro-eye patch.
3. The method according to claim 2, wherein in step 1), the molecular weight of the small molecule hyaluronic acid is 1-100 tens of thousands;
the concentration of the small molecule hyaluronic acid aqueous solution is 5-150mg/mL.
4. The method according to claim 2, wherein in step 2), the molecular weight of the macromolecular hyaluronic acid is 20-200 ten thousand, and the concentration of the macromolecular hyaluronic acid aqueous solution is 1-40mg/mL;
the molecular weight of the small molecule hyaluronic acid is 1-100 ten thousand; the concentration of the small molecule hyaluronic acid aqueous solution is 5-150mg/mL.
5. The method according to claim 2, wherein the aqueous solution of large molecule hyaluronic acid is mixed with the aqueous solution of small molecule hyaluronic acid in a volume ratio of 1:1-1:100.
6. Use of the composite micro-eye patch of claim 1 in the manufacture of a product for ocular skin care.
7. The use according to claim 6, wherein in said use, said product for ocular skin care is used for the treatment and repair of ocular skin aging, collagen loss caused by aging or disease.
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