CN104826228B - For skin repair and the biological paste of maintenance - Google Patents
For skin repair and the biological paste of maintenance Download PDFInfo
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- CN104826228B CN104826228B CN201510268656.6A CN201510268656A CN104826228B CN 104826228 B CN104826228 B CN 104826228B CN 201510268656 A CN201510268656 A CN 201510268656A CN 104826228 B CN104826228 B CN 104826228B
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- micropin
- skin
- microneedle array
- raw material
- maintenance
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Abstract
The application is related to a kind of biological paste for being used for skin repair and maintenance with different release gradients, and it has more preferable skin repair and cosmetic result, and this biological paste is made up of two parts, is used cooperatively：One includes substrate and multiple micropins in substrate, and another is back of the body coating, is also gel cold compress layer.The microneedle array of solubility first, the second microneedle array of upper surface of substrate.First microneedle array has different dissolution velocities from the second microneedle array.First microneedle array includes some first micropins, and the second microneedle array includes some second micropins.
Description
Technical field
The application is related to a kind of biological paste, in particular it relates to it is a kind of with it is different release gradients be used for skin repair with
The biological paste of maintenance.
Background of invention
How human senescence is resisted, it is the eternal topic of beauty treatment fields skin is improved elastic, anti-aging.Human body occurs
During aging, skin of face can form wrinkle and color spot.Drug cosmetics and surgery beauty are two kinds of main intervention forms, but skin
Particularly cuticula has barrier action to Drug Percutaneous Absorption, and absorption of the skin to medicine, surgery are beautiful when hindering drug cosmetics
Container has the shortcomings that applicability is not wide, risk is high, complication and side effect are more, and drug cosmetics and surgery beauty usually can be by
Improper generation pain and spot are controlled or operate in dosage.In recent years, a kind of microneedle patch for beauty, or make a living
Thing patch is increasingly used by users, and this micropin has higher security and nonirritant.This biological paste include substrate and
Multiple micropins in substrate, alternatively also include back of the body coating, the thing of such as skin repair and beauty is applied on the micropin
Matter, or micropin directly is made in itself in the solid-like of these materials, back of the body coating is affixed on into microneedle substrate face in use leads to
Finger pressure micropin back of the body coating is crossed gradually to be absorbed by the body.
The skin of human body has three-layer weave：Positioned at outermost cuticula, living Epidermis's layer and positioned at innermost corium
Layer.Cuticle thickness is about 30~50 microns, is made up of the horn cell of densification, its permeability to most medicines is very
Low, being these medicines passes through the major obstacle that percutaneously conveys；Skin layer thickness is about 50~100 microns, containing competent cell and
Minimal amount of nerve fiber, but there is no blood vessel；It is skin corium below epidermis, it is the chief component of skin, is contained
Substantial amounts of living cells, nerve fiber and vascular tissue.Conventional subcutaneous injection needs professional to be operated, and syringe needle external diameter is general
For 0.4~3.4 millimeter, syringe needle need to penetrate skin and be deep into muscle, can touch blood vessel and damage a large amount of nerve fibers, usually draw
Play patient's bleeding and pain.And use microneedle array, pressing apply pin by way of can moment in keratoderma and epidermis
Layer produces the duct of a large amount of micron dimension sizes, so as to significantly improve the permeability of medicine.Because micropin medicine-feeding part is in body surface
Nerve fiber and blood vessel are not touched, therefore will not produce pain and bleeding；In addition, need not be special using micropin administration
Industry personnel are operated, flexible and convenient to use, can interruption of the administration at any time, so being easier to be easily accepted by the patient.In addition, micropin pierces
The stratum corneum barrier for wearing skin produces the capillary network that microchannel makes medicine penetrate into dermal layer of the skin by micropin hole, with blood
The through treatment target position of liquid circulation, can reach and quickly and efficiently absorb the drug or the purpose of cosmetic material, at the same micropin stimulate it is true
Cortex, percutaneous self-healing ability promote ossein hyperplasia, and micropin can improve the absorptivity of medicine and reduce the wave of medicine
Take.Further, since micropin is thin and sharp, paracentesis depth does not contact nerve endings only in cuticula and dermis, therefore to body
The degree of injury of tissue reduces.
Micropin biological paste includes many different forms at present, soluble micro- mainly including solid microneedles, empty micropin
Pin.Wherein, solid microneedles are generally formed by polymer insoluble in skin, monocrystalline silicon and metal, and drug coat is micro-
Pin outer surface；Empty micropin is that each micropin includes a passage, applies medicine by passage target area on earth from substrate,
Empty micropin has the advantages of continuing, controllable drug delivery；Soluble micropin refers to that micropin is made up of medicine in itself, and biological paste is pressed
After on to human body skin, micropin gradually dissolves, last only to peel off residual substrate layer from skin, with pain it is small,
The advantages that easy to operate.
Specific to the biological microneedle patch for skin repair and beauty, it can be solid microneedles, and microneedle array surface applies
It is covered with skin repair and cosmetic material is pierced into skin again, or skin repair and beauty thing is applied again after microneedle array is pierced into skin
Matter.Biological microneedle patch for skin repair and beauty can be soluble micropin, and microneedle array is repaiied by having to skin in itself
Multiple and cosmetic result material is formed, and micropin is integrally formed, and each micropin shape is identical and including identical material, during use not
A point gradient can be carried out to skin to be administered.
The content of the invention
The application provides a kind of biological paste for being used for skin repair and maintenance with different release gradients, and it has more preferable
Skin repair and cosmetic result.
According to biological paste described herein, including substrate, the microneedle array of solubility first positioned at upper surface of substrate,
Two microneedle arrays and back of the body coating.First microneedle array has different dissolution velocities from the second microneedle array.First micropin battle array
Row include some first micropins, and the second microneedle array includes some second micropins.
In one embodiment, the back of the body coating in biological paste can play cold compress effect and can as adhered layer and strengthen giving birth to
Thing pastes the bonding force with skin.
The arrangement of first microneedle array, the second microneedle array can arbitrarily be set as needed, for example, independent first micropin with
It is arranged at intervals between second micropin, or the first micropin, the second micropin are arranged in column, each micropin of row first and each row second are micro-
Pin is arranged at intervals, or the first micropin, the second micropin lopping arrangement, and each first micropin that encloses is arranged at intervals with the second micropin of each circle.
First micropin includes kernel and controlled-release coating, and the second micropin is integrally formed.
The kernel of first micropin and the second micropin can be made up of same micropin raw material, raw material be 30K~
The non-crosslinked hyaluronic acid of the non-crosslinked hyaluronic acid of 4000000 dalton, preferably 500~2000000 dalton, Huo Zhewei
The mixture of PVA and hyaluronic acid is to realize the transdermal control of large hydrophilic molecular such as albumen, polypeptide, DNA, RNA and other drugs
Release.
Prior art fully proves：Hyaluronic acid has moisturizing, maintenance and trophism to skin, and it can be pinned greatly
Measure hydrone, skin is kept full high resilience, reduce wrinkle, can also mild dilation capillary, increase blood circulation, change
Kind intermediate supersession, promotes the absorption of skin-nourishing and the discharge of waste, and hyaluronic acid is good transdermal again while moisturizing
Sorbefacient.The non-crosslinked hyaluronic acid of the dalton of 30K~4000000, preferably 500~2000000 dalton is non-crosslinked
Micropin intensity made of hyaluronic acid is high, and absorption efficiency is high, soak time is lasting.
In one embodiment, micropin raw material are that the molecular weight of different molecular weight is the dalton of 30K~3000000
The mixing of non-crosslinked hyaluronic acid, is preferably also mixed with cross-linked-hyaluronic acid, and cross-linked-hyaluronic acid can be natural crosslinking
Hyaluronic acid, or the hyaluronic acid with BDDE crosslinking.It is demonstrated experimentally that molecular weight be 30K~
Micropin intensity made of the non-crosslinked hyaluronic acid of 3000000 dalton is high, and the hyaluronic acid for mixing different molecular weight not only enters
One step improves micropin intensity, and it is slow to be easy to degradation speed in dissolving, skin in skin so that cosmetic result is more preferable, more holds
Long.
It is highly preferred that active component can be added in biological paste raw material：Skin moisturizer, such as glycerine or intermediate filament are related
Albumen；Beneficial to the vigor and nutriment of skin repair, such as：Stem cell, EGF, vitamin C, vitamin A or dimension
Raw plain E, chestnut stoste, rice bran stoste, Chinese yam stoste etc.；Skin-whitening agents, such as：Hydroquinones, ursin, kojic acid, hydroxyl
Acetic acid or niacinamide etc..
In a detailed embodiment, micropin raw material are that molecular weight is the non-crosslinked of the dalton of 30K~3000000
Bright matter is sour, natural cross-linked-hyaluronic acid, fat stem cell, EGF, vitamin E, hydroquinones, chestnut stoste, rice
Chaff stoste, Chinese yam stoste, high-molecular gel, glycerine etc..
In another embodiment, formed gel adhered layer raw material include chestnut stoste, rice bran stoste,
Chinese yam stoste, high-molecular gel, glycerine etc., help that there is cold compress effect when being bonded on skin to skin.
Stem cell is a kind of multipotential cell with self-renewing, infinite copy and Multidirectional Differentiation ability, and medical field claims
For " general-purpose cell ".Wherein, fat stem cell has extremely strong in-vitro multiplication ability, can be to fat, bone, muscle, endothelium, pancreas
The cell such as island, nerve direction breaks up.Compared with other stem cells, there is fat stem cell biological characteristics to stablize, source is sufficient,
The advantages such as easy acquisition and condition of in vitro culture are simple.Fat stem cell can with secrete cytokines and growth factor, play nutrition,
The function of the senile cell of body injury is repaired and replaced, antioxidant, scavenging activated oxygen, heat shock protein can also be provided
To part, local toxicity material is eliminated, promotes cell and tissue repair, in addition, fat stem cell can increase collagen egg
White secretion, swallows pigment removal color spot, improves skin elasticity, therefore fat stem cell has extraordinary crease-resistant, nti-freckle effect
Fruit.
EGF, which can promote cytotrophy material to be transported to from extracellular active, into the cell, increases intracellular battalion
Support.Promote corium confluent monolayer cells secretion synthesis collagenous fibres, make dermal tissue full, so as to reduce and smooth away wrinkles.In addition, epidermis
Growth factor has the accumulation such as stronger facilitation, and residual of less pigment and dead cell to the propagation of epidermal cell,
Color spot and pigmentation are eliminated, goes out cutaneous manifestations tender white.Therefore, EGF, which also has, smoothes away wrinkles and prevents color spot
Effect.
Chestnut stoste contains the nutriments such as carbohydrate, starch, protein, fat, vitamin B1 and B2, according to《Compendium of Materia Medica》
Record：Chestnut " it is smash scattered, and sweet painting face, make light suddenly remove wrinkle ".
Rice bran stoste, which helps skin, becomes that water is tender, bright, and long-term use can be with skin whitening, can be with decontamination for having one's hair wash
Maintaining hair simultaneously.Shown according to modern study, abundant vitamin A, B1, B2, C, E, amino acid and nicotinic acid etc. are contained in rice bran
It nutriment needed for skin, can stimulate circulation, accelerate the metabolism of Skin Cell.In addition, also containing rich in rice bran
Rich cytotrophy composition and the bioactie agent of multiple functions, can delaying skin aging.Can be to spot, wrinkle, coarse, dark sore
Or the skin of surface moisture deficiency is effectively improved.Also there is the function of moisturizing, can effectively prevent scaly dry skin, delaying skin
Aging, the effect for preventing pigment deposition；According to《Japanese agriculture news》In report, Korean and Japanese university's young scientist Yamamoto great generation, use old
The comparative experiments result that mouse is carried out shows that the effect that the ceramide glucoside extracted from rice bran suppresses melanin generation is
29%, 39% than the kojic acid with same effect is slightly lower.Yamamoto is said, compared with other materials, ceramide glucoside is
A kind of safer cosmetic material, because it does not contain the toxin of the cell of attack manufacture pigment, while it can also mitigate ultraviolet
Injury of the line to skin.So skin wet, fair and clear can be made.
Controlled-release coating is preferably bioabsorbable medical grade substance, and its dissolution velocity in skin is more former than above-mentioned micropin
The dissolution velocity of material is slow, the silicon coating formed for example with porous silicon particle, or uses bioabsorbable polymer,
Such as poly- DL- lactides, polylactide -co- second lactide；Polylactide -co- polycaprolactone, it is poly- (L- lactide-cos-
1,3-PD carbonic ester), poly- 1,3-PD carbonic ester and copolymer；Poly butyric ester and copolymer；Poly- hydroxypentanoic acid
Ester and copolymer；Poe and copolymer；Polyanhydride and copolymer；Poly- iminocarbonic ester and copolymer.
When using the biological paste of the application, first the skin of target area is cleaned, dried, then by the biology of the application
Back of the body coating in patch is entirely attached on human body skin after being affixed on microneedle substrate face, is carried on the back coating by finger pressure micropin, is made micropin battle array
Row are pierced into human body skin, the second microneedle array directly starts to dissolve, discharge active ingredient and the first microneedle array due to outer layer painting
Cover controlled-release coating, through after a period of time, such as just start after the second microneedle array is completely dissolved to dissolve, discharge effectively into
Point, so as to realize that a point gradient is administered.The biological paste of the application includes the non-crosslinked hyaluronic acid of the dalton of 30K~4000000, excellent
Select micropin intensity made of the non-crosslinked hyaluronic acid of 500~2000000 dalton high, and absorption efficiency is high, soak time is held
Long；The hyaluronic acid or cross-linked-hyaluronic acid for mixing different molecular weight not only further improve micropin intensity, and in skin
It is easy to dissolving, degradation speed is slow in skin so that cosmetic result is more preferable, more longlasting；Add stem cell, EGF, chestnut
Sub- stoste, rice bran stoste, Chinese yam stoste, acted synergistically with hyaluronic acid, can further improve that biological paste is crease-resistant, effect of nti-freckle
Fruit.
Brief description of the drawings
Fig. 1：According to the front view of biological paste described herein；
Fig. 2：According to the top view of biological paste described herein；
Fig. 3：The zoomed-in view of first micropin.
Embodiment
Referring to accompanying drawing 1,2, according to biological paste described herein, including substrate 1, and positioned at the upper surface of substrate 1 can
The first microneedle array of dissolubility A, the second microneedle array B.Microneedle array A has different dissolution velocities from microneedle array B.Micropin battle array
Row A includes some first micropin a, and microneedle array B includes some second micropin b.In one embodiment, the back of the body of biological paste applies
Layer can play the bonding force that cold compress effect and can strengthens biological paste and skin as adhered layer.
Microneedle array A, microneedle array B arrangement can arbitrarily be set as needed, such as independent first micropin and second micro-
It is arranged at intervals between pin, or micropin a, micropin b arrange in column, each row micropin a and each row micropin b is arranged at intervals, Huo Zhewei
Pin a, micropin b lopping arrangement, each micropin a and each circle micropin b that encloses are arranged at intervals.
Relative to micropin b, micropin a outer layers also include one layer of controlled-release coating 3, that is to say, that micropin a includes kernel 4 and sustained release
Coating 3, as shown in Figure 3.
Micropin a kernel 4 and micropin b can be made up of same micropin raw material, and raw material are hyaluronic acid, Huo Zhewei
The mixture of PVA and hyaluronic acid is to realize the transdermal control of large hydrophilic molecular such as albumen, polypeptide, DNA, RNA and other drugs
Release.
More specifically, micropin raw material are molecular weight be the dalton of 30K~3000000 non-crosslinked hyaluronic acid or mixing
The hyaluronic acid or cross-linked-hyaluronic acid of different molecular weight, cross-linked-hyaluronic acid can be natural cross-linked-hyaluronic acids, or
Person and the hyaluronic acid of BDDE crosslinking.It is demonstrated experimentally that molecular weight is the dalton of 30K~3000000
Non-crosslinked hyaluronic acid made of micropin intensity it is high, mixing the hyaluronic acid of different molecular weight, not only further to improve micropin strong
Degree, and be easy to dissolving in skin, degradation speed is slow in skin so that cosmetic result is more preferable, more longlasting.
Active component can be added in biological paste raw material：Skin moisturizer, such as glycerine or filaggrin；It is beneficial to
The vigor and nutriment of skin repair, such as：Stem cell, EGF, vitamin C, vitamin A or vitamin E, chestnut
Stoste, rice bran stoste, Chinese yam stoste etc.；Skin-whitening agents, such as：Hydroquinones, ursin, kojic acid, hydroxyacetic acid or nicotinoyl
Amine etc..
In a detailed embodiment, micropin raw material are that molecular weight is the non-crosslinked of the dalton of 30K~3000000
Bright matter is sour, natural cross-linked-hyaluronic acid, back of the body coating raw material be fat stem cell, EGF, vitamin E, to benzene two
Phenol, chestnut stoste, rice bran stoste, Chinese yam stoste, high-molecular gel, glycerine etc..
The preferably bioabsorbable medical grade substance of controlled-release coating 3, its dissolution velocity in skin are more former than above-mentioned micropin
The dissolution velocity of material is slow, the silicon coating formed for example with porous silicon particle, or uses bioabsorbable polymer,
Such as poly- DL- lactides, polylactide -co- second lactide；Polylactide -co- polycaprolactone, it is poly- (L- lactide-cos-
1,3-PD carbonic ester), poly- 1,3-PD carbonic ester and copolymer；Poly butyric ester and copolymer；Poly- hydroxypentanoic acid
Ester and copolymer；Poe and copolymer；Polyanhydride and copolymer；Poly- iminocarbonic ester and copolymer.
When using the biological paste of the application, first the skin of target area is cleaned, dried, then by the biology of the application
Back of the body coating in patch is affixed on microneedle substrate face carries on the back coating by finger pressure micropin makes microneedle array be pierced into human body skin, microneedle array B
Directly start to dissolve, discharge active ingredient and microneedle array A due to outer layer coating controlled-release coating 3, through after a period of time, example
Such as just start to dissolve after microneedle array B is completely dissolved, discharge active ingredient, so as to realize that a point gradient is administered.
Claims (7)
1. a kind of be used for skin repair and the biological paste of maintenance, including substrate with different release gradients, and positioned at substrate
The microneedle array of solubility first, the second microneedle array of upper surface；It is characterized in that：
First microneedle array has different dissolution velocities from the second microneedle array；Wherein the first microneedle array includes some first
Micropin, the second microneedle array include some second micropins；
Wherein the first micropin includes kernel and controlled-release coating, and the second micropin is integrally formed, wherein the kernel of the first micropin and
Two micropins can be made up of same micropin raw material；The micropin raw material are that molecular weight is the non-of the dalton of 30K~4000000
Cross-linked-hyaluronic acid is the mixing that the molecular weight of different molecular weight is the non-crosslinked hyaluronic acid of the dalton of 30K~3000000；
It is arranged at intervals between independent first micropin and the second micropin, or the first micropin, the second micropin are arranged in column, each row
First micropin and each micropin of row second are arranged at intervals, or the first micropin, the second micropin lopping arrangement, it is each enclose the first micropin with it is each
Enclose the second micropin interval setting；
Also include gel sticking layer in the substrate, it can play cold compress effect and can as adhered layer and strengthen biological paste and skin
The bonding force of skin.
2. according to claim 1 also include being coated in base for skin repair and the biological paste of maintenance, wherein biological paste
The adhesive layer of bottom upper surface, it can strengthen the bonding force of biological paste and skin.
3. it is according to claim 1 or 2 for skin repair with maintenance biological paste, wherein micropin raw material be 30K~
The non-crosslinked hyaluronic acid of 4000000 dalton.
4. it is according to claim 3 for skin repair with maintenance biological paste, wherein micropin raw material be 500~
The non-crosslinked hyaluronic acid of 2000000 dalton.
5. according to claim 1 for skin repair and the biological paste of maintenance, wherein micropin raw material are different molecular
The mixture of the non-crosslinked hyaluronic acid of 500~2000000 dalton of amount.
6. it is according to claim 5 for skin repair and the biological paste of maintenance, also include handing over wherein in micropin raw material
Join hyaluronic acid.
7. it is according to claim 6 for skin repair and the biological paste of maintenance, skin is wherein also included in micropin raw material
Skin NMF, stem cell, EGF, vitamin C, VitAVitE, chestnut stoste, rice bran stoste, Chinese yam are former
One or more in liquid, hydroquinones, ursin, kojic acid, hydroxyacetic acid or niacinamide；In the raw material of gel adhered layer
Including the one or more in chestnut stoste, rice bran stoste, Chinese yam stoste, high-molecular gel, glycerine.
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| CN201510268656.6A CN104826228B (en) | 2015-05-25 | 2015-05-25 | For skin repair and the biological paste of maintenance |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201510268656.6A CN104826228B (en) | 2015-05-25 | 2015-05-25 | For skin repair and the biological paste of maintenance |
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| CN104826228B true CN104826228B (en) | 2017-12-29 |
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| KR102547455B1 (en) * | 2017-05-30 | 2023-06-23 | 닛샤 가부시키가이샤 | Microneedle patch and package thereof |
| JP7345792B2 (en) * | 2017-09-19 | 2023-09-19 | エルジー ハウスホールド アンド ヘルスケア リミテッド | Hyaluronic acid filler using microneedle patch |
| CN107648589A (en) * | 2017-11-28 | 2018-02-02 | 苏州汇涵医用科技发展有限公司 | A kind of skin repair gel and preparation method thereof |
| WO2019143293A1 (en) * | 2018-01-16 | 2019-07-25 | Nanyang Technological University | Self-implantable micro-drug-reservoirs for localized and controlled ocular drug delivery |
| CN108325068A (en) * | 2018-04-04 | 2018-07-27 | 陈彦彪 | A kind of auxotype solubility micropin and micropin slide glass |
| CN108607157A (en) * | 2018-04-18 | 2018-10-02 | 北京化工大学 | A kind of soluble crosslinking-non-crosslinked compound micropin of hyaluronic acid |
| US11318292B2 (en) * | 2018-05-28 | 2022-05-03 | Microneedles Inc. | Microneedle patch for transdermal injections |
| CN111686309A (en) * | 2019-04-09 | 2020-09-22 | 珠海天威飞马打印耗材有限公司 | Preparation method of 3D printed skin |
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