CN108969880A - A kind of solubility micropin film and preparation method thereof - Google Patents

A kind of solubility micropin film and preparation method thereof Download PDF

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CN108969880A
CN108969880A CN201810598273.9A CN201810598273A CN108969880A CN 108969880 A CN108969880 A CN 108969880A CN 201810598273 A CN201810598273 A CN 201810598273A CN 108969880 A CN108969880 A CN 108969880A
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micropin
film
preparation
soluble
mold
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CN108969880B (en
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韩韦红
葛翠兰
钱锵
曹小霞
万睿
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SHANGHAI BAIYI BIOLOGICAL ENGINEERING Co Ltd
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SHANGHAI BAIYI BIOLOGICAL ENGINEERING Co Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0019Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0021Intradermal administration, e.g. through microneedle arrays, needleless injectors
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M37/00Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M37/00Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0023Drug applicators using microneedles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M37/00Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0046Solid microneedles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M37/00Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0053Methods for producing microneedles

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  • Health & Medical Sciences (AREA)
  • Dermatology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Biomedical Technology (AREA)
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  • Heart & Thoracic Surgery (AREA)
  • Anesthesiology (AREA)
  • Medical Informatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Cosmetics (AREA)
  • Medicinal Preparation (AREA)
  • Media Introduction/Drainage Providing Device (AREA)

Abstract

The invention discloses a kind of soluble micropin films and preparation method thereof, and preparation method includes following operating procedure: A1) preparation of micropin mold;A2) the preparation of premixed solution;A3) the molding of micropin film;A4 it) demoulds, encapsulate, sterilizing.After soluble micropin film is mixed in proportion by Sodium Hyaluronate, water soluble chitosan, other function component, it is prepared according to method provided by the invention.The present invention is produced using the groove structure mold through Laser Micro-Machining, and production process is simple and convenient, suitable for scale production;Solubility micropin film provided by the invention, film-strength are able to satisfy requirement, have moisturizing, promote reparation, antibacterial, whitening and anti-aging function.

Description

A kind of solubility micropin film and preparation method thereof
Technical field
The present invention relates to beauty and percutaneous drug delivery field, and in particular to a kind of solubility micropin film and preparation method thereof.
Background technique
Micropin technology is widely applied in beauty treatment fields and percutaneous drug delivery field at present.Micropin be it is a kind of by metal, The materials such as silicon, polymer are made, length is 25~2000 μm, needle point is micron-sized in symmetrical conical or asymmetric scarf Array structure.Soluble micropin generally by can the high molecular material of biological dissolution or degradation be prepared, be coated on soluble micro- Bioactive substance in needle is gradually released and is played a role with dissolution of the soluble material in skin.It is soluble micro- Needle has better biocompatibility and bigger drugloading rate than insolubility micropin, receive more and more attention and grind Study carefully.Soluble micropin film is widely used on America and Europe, Japan and Korea S and other places, is applied to resisting age of skin, desalination wrinkle, repairs fibre Significant effect in terms of the beauty such as dimension elasticity, treatment acne, removal dead skin.
Ideal solubility beauty micropin film should have following feature: 1) safety, will not cause to infect;2) it imitates Fruit property, the effects of anti-aging, whitening can be reached;3) practicability, the strength of materials are met the requirements;4) cost performance, micropin film produced Journey is simply, conveniently, suitable for scale production.
Currently, the material for being used to prepare soluble micropin film mostlys come from Sodium Hyaluronate, and it is added as needed Its ingredient is to enhance cosmetic result, such as collagen, polysaccharose substance and glycerol ingredient is added, and can enhance the strong of micropin film Degree, promotees prosthetic and whitening and other effects at moisture retention.
Sodium Hyaluronate is called sodium hyaluronate, is that one kind is widely present in vertebrate connective tissue, mucous tissue, eyeball Crystalline lens and certain bacteriums folder film in polysaccharide material, play key player in human skin skin corium, to keep skin Skin spring function plays an important role.With age, Sodium Hyaluronate loss speed is faster than the speed of growth in skin, leads to flesh Skin gradually loses gloss elasticity, the aging phenomena such as wrinkle occurs.The Sodium Hyaluronate of studies have shown that exogenous supplement also has machine The holding skin elasticity function of the original Sodium Hyaluronate of body rises and slows down aging action.It and is a kind of effective by micropin technology Exogenous supplement Sodium Hyaluronate mode.
It take Sodium Hyaluronate as the micropin of main host material preparation, after it is pierced into human skin, Sodium Hyaluronate will It dissolves and is stranded in skin under liquid effects, play beautification function.High molecular Sodium Hyaluronate hydrophily is strong, can inhale The moisture for receiving 1000 times of own vol, can quickly fill and lead up the fine wrinkles of skin, but solution viscosity is with concentration after water swelling Increase and sharply increase, this is unfavorable for the production of micropin injection molding;Low molecular Sodium Hyaluronate can stimulate in skin in collagen The generation of albumen increases the elasticity and plumpness of skin, but needle body mechanical strength is not enough to be pierced into skin.It can be seen that only with single point The Sodium Hyaluronate of son amount cannot meet production and the performance requirement of micropin simultaneously.
The preparation process of soluble micropin mainly by by functional liquid inject micropin mold, drying later, stripping, cutting and ?.Micropin mold is a key factor of micropin production cost, production operation simplicity.Currently, domestic micropin mold is general After the solid formpiston micropin prepared before this by micro electro mechanical processing or chemical etching, mould is answered by PDMS and obtains former, it will be pre- Mixed perfusion obtains after dry in former.In this technique, mould is answered by formpiston and is that former process is complicated, prepares micropin to subsequent Production and processing make troubles, and these preparation methods are complicated, expensive, lead to the increased costs of micropin product, for The price of consumer is also very high always, and drop is not got off.
In recent years, domestic the preparation of micropin product is had made intensive studies: wherein Publication No. CN103893018A Sodium Hyaluronate micropin involved in Chinese patent lowers its mechanical performance because joined hyperbranched polysulfones amine or polyester, and And easy mold release, micropin molding be not poor during the preparation process.The Chinese patent of Publication No. CN102178616B, a kind of sodium hyaluronate are micro- Needle pad pasting and preparation method thereof, the needle adhesive film are made of sodium hyaluronate, collagen, polyalcohol, efficacy active component etc., but should Patent is not related to the molecular weight of sodium hyaluronate, causes injection molding in production process difficult.In Chinese patent CN101687090B Mention hyaluronic acid micropin, but the standby micropin of the patent system is in addition to containing hyaluronic acid, also includes 50%~70% glue Former albumen.It has been reported that inflammatory reaction, and the patent can be caused after the microneedle patch containing collagen is pierced into skin Preferably molecular weight is 400,000 or more Sodium Hyaluronate, is also unfavorable for casting film-forming or injects in the micropore of micropin mold.In It is mentioned in state patent CN104027324 A by chitosan, collagen, the micropin of Sodium Hyaluronate preparation, but the patent provides Preparation method complex process, be not suitable for industrialization production.Chinese patent CN105078880A and CN201610913515 institute It joined chitosan and Sodium Hyaluronate in the composition for the micropin film stated, but not clear to the Sodium Hyaluronate of which kind of specification It limits, it cannot be said that the function of bright hyaluronic acid.It is also mentioned that the hyalomitome of two kinds of molecular weight in Chinese patent CN107184417A Sour sodium shares, but does not account for antibiotic property, and in addition the patent needs to prepare respectively, pours needle point liquid and substrate liquid, and process is numerous It is trivial, it is unfavorable for industrialization production.
In conclusion the preparation process of water solubility micropin there has been no a kind of can completely consider safety, practical at present Property, whitening anti-aging effect and optimize production line technique.
Summary of the invention
The purpose of the present invention is to provide a kind of soluble micropin membrane preparation method, which uses Laser Micro-Machining Groove structure mold produced, production process is simple to operate, suitable for scale production;Mold energy Reusability, benefit In reducing cost.Requirement is able to satisfy by the strength of materials of the soluble micropin film of its method preparation.
Present invention simultaneously provides a kind of soluble micropin film, specifically it is to provide and a kind of protects having of generally acknowledging of modern times Wet, rush repair function Sodium Hyaluronate and the water soluble chitosan composition with moisturizing, rush reparation, antibacterial functions are newly formulated, And other function ingredient is added, such as glycerol, pentanediol, hexylene glycol, water soluble collagen, epidermal growth factor, vitamin C, rice bran stoste or arbutin etc. is one or more, and being prepared into has the function of moisturizing, promotees reparation, antibacterial, whitening and anti-aging Soluble micropin film.
The present invention provides a kind of preparation method of soluble micropin film, including following operating procedure:
A1) the preparation of micropin mold: using laser micro-machining system, and progress laser is micro- on special groove structure mold adds Work obtains micropin mold, which can Reusability;
A2) the preparation of premixed solution: will be in macromolecule Sodium Hyaluronate, small-molecular-weight Sodium Hyaluronate, water soluble chitosan It is one or more mixed with purified water, stirring and dissolving;Other function substance is added in the completely backward system of dissolution, as glycerol, One of pentanediol, hexylene glycol, water soluble collagen, epidermal growth factor, vitamin C, rice bran stoste or arbutin or It is a variety of, it is uniformly mixed and vacuumizes bubble removing up to premixed solution;
A3) moulding of micropin film, molding: premixed solution is disposably poured into special micropin mold, vacuumizes, dries later Case is dry;
A4) demould, encapsulate, sterilizing: removing demoulds up to soluble micropin film, cuts, and encapsulation finally carries out irradiation sterilization.
The present invention also advanced optimizes a kind of mold for preparing soluble micropin film: the mold be use by wavelength for The laser micro-machining system of 355nm purple light carries out Laser Micro-Machining to molding groove structure mold under certain parameter, leads to Laser power and process velocity are overregulated to adjust the taper and smoothness of micropin length, external morphology, to obtain for making The mold of standby solubility micropin film, further optimizes soluble micropin film die.
Preferably, the molding groove structure mold includes crescent, rectangle, rectangular, diamond shape, circle or ellipse Shape, groove height are 5~50mm, 1~100 μm of groove inner surface horizontal departure;
Preferably, the side plate (1) of the micropin mold and microneedle array (2) distance are 5~50mm, and micropin mold height is 10~100mm, micropin die width are 50~1000 mm;
Preferably, the material of the micropin mold includes stainless steel material, polytetrafluoroethylene (PTFE), silica gel, PDMS.
The present invention also provides a kind of soluble micropin films mainly by Sodium Hyaluronate, water soluble chitosan and other function Group is grouped as;
The Sodium Hyaluronate is 10~100 kDa Sodium Hyaluronate of 500~2000 kDa of macromolecule and small-molecular-weight One or both of;
The water soluble chitosan is carboxymethyl chitosan, chitosan hydrochloride, chitosan quaternary ammonium salt, chitosan lactate, shell The one or more of glycan sulfuric ester, chitosan oligosaccharide, hyaluronic acid-like chitosan;
The other function component be glycerol, pentanediol, hexylene glycol, water soluble collagen, epidermal growth factor, vitamin C, The one or more of rice bran stoste or arbutin.
The macromolecule Sodium Hyaluronate of the solubility micropin film, small-molecular-weight Sodium Hyaluronate, water soluble chitosan, The weight content of other function component is respectively 0~3%: 0~15%: 0~3%: 0~2%, remaining as purified water Content.
The micropin component prepares soluble micro- according to a kind of preparation method of soluble micropin film of the application Needle film, has the feature that
Preferably, the micropin is cone, triangular pyramidal, quadrangle taper, hexagonal pyramidal, crescent;
Preferably, the length of the micropin is 10~3000 μm;
Preferably, the base diameter of the micropin is 50~1000 μm;
Preferably, the spacing of the micropin is 50~3000 μm.
Under the conditions of the specification that the present invention limits, the soluble micropin film for enabling to the present invention to obtain is effective rapidly in time Functional component is inputted target effect site by ground, is played moisturizing, is promoted reparation, antibacterial, whitening and anti-aging function, while the application Soluble micropin film have higher-security, will not cause to infect.
In conclusion beneficial effects of the present invention:
1, soluble micropin membrane preparation method provided by the invention, for the mold of structure obtained in Laser Micro-Machining, fluted On be irrigated the solution of the different component containing beauty functions and prepare micropin film through moulding, molding, demoulding, encapsulation, sterilizing, This method is simple to operate, suitable for scale production;The mold of structure that Laser Micro-Machining obtains, fluted can make repeatedly With conducive to production cost is reduced;Requirement is able to satisfy by the strength of materials of the soluble micropin film of its method preparation.
2, the mold that one of present invention prepares soluble micropin film can be prepared by laser micro-machining system, The taper and smoothness of micropin length, external morphology are adjusted by adjusting laser power and process velocity, so that the present invention can It to significantly simplify processing step, further reduces the cost, is convenient for industrialization production, there is very strong practicability.
3, the groove height of micropin mold is 5~50mm, can be used for the solution that loading prepares micropin film, is conducive to primary fill Note;1~100 μm of groove inner surface horizontal departure, conducive to preparation micropin film is smooth, thickness is uniform;The side plate of micropin mold It (1) is 5~50mm with microneedle array (2) distance, convenient for removing of the micropin film after dry.It is prepared using this micropin mold micro- Needle film, it is simple to operate, it is suitable for scale production.
4, the present invention passes through the concentration and component for changing micropin premixed solution, and the Sodium Hyaluronate for overcoming small-molecular-weight obtains The micropin film mechanical strength arrived is inadequate;The Sodium Hyaluronate of macromolecule because viscosity large fluidity is bad, is unable to get knot again The problem of structure uniform micropin film, the soluble micropin film of intensity and good toughness can be prepared.
5, the small-molecular-weight Sodium Hyaluronate used in the present invention has moisturizing, promotees reparation, anti-inflammatory, bacteriostasis, and water Also moisturizing, rush reparation, antibacterial action, the two play synergistic effect to soluble chitosan, and cosmetic result is more preferably.
6, the other function component in micropin film of the present invention, glycerol, pentanediol, hexylene glycol play better moisture-keeping function; Water soluble collagen, epidermal growth factor have good anti-aging effects, while in vitamin C, rice bran stoste, arbutin Play the role of good whitening.
7, the needle body mechanical strength of micropin film of the present invention is enough, can successfully be pierced into keratoderma, can be effectively by micropin Film functional component inputs target effect site, works rapidly, can play apparent moisturizing, promote reparation, antibacterial, whitening and anti-ageing Old effect.
Detailed description of the invention
Fig. 1 micropin die structure dwg.
The micropin membrane sample of Fig. 2 preparation.
Fig. 3 micropin micro-structure diagram.
Specific embodiment
The present invention is further explained combined with specific embodiments below, cited specific embodiment is only several preferred sides Formula is not construed as limiting the scope of the invention.
Embodiment 1:
The soluble micropin film major function of the present embodiment is moisturizing, promotees reparation and antibacterial, and specific preparation process is as follows:
1, the preparation of micropin mold: using wavelength for the laser micro-machining system of 355nm purple light, contains groove structure special Stainless steel mould on carry out Laser Micro-Machining, the micropin mold needle point of acquisition is cone shape, and the length of needle point is 100 μ M, the base diameter of needle point are 600 μm, and the spacing between needle point is 300 μm, the number of per square centimeter on average micropin needle point About 300;
2, the preparation of premixed solution: by macromolecule Sodium Hyaluronate 1g, small-molecular-weight Sodium Hyaluronate 8g, carboxymethyl chitosan 1g and purified water 89g mixing, stirring and dissolving;Glycerol 1g is added in the completely backward system of dissolution, is uniformly mixed and vacuumizes degasification It steeps up to premixed solution;
3, the moulding of micropin film, molding: premixed solution is disposably poured into special micropin mold, is vacuumized, drying is dry It is dry;
4, demould, encapsulate, sterilizing: removing demoulds up to soluble micropin film, cuts, and encapsulation finally carries out irradiation sterilization.
Embodiment 2:
The soluble micropin film major function of the present embodiment is anti-aging, moisturizing, promotees reparation and antibacterial, and specific preparation step is such as Under:
1, the preparation of micropin mold: using wavelength for the laser micro-machining system of 355nm purple light, contains groove structure special Teflon mould on carry out Laser Micro-Machining, the micropin mold needle point of acquisition is cone shape, and the length of needle point is 150 μm, the base diameter of needle point is 500 μm, and the spacing between needle point is 600 μm, per square centimeter on average micropin needle point Number be about 144;
2, the preparation of premixed solution: by macromolecule Sodium Hyaluronate 2g, small-molecular-weight Sodium Hyaluronate 10g, chitosan hydrochloric acid Salt 1g and purified water 86.4g mixing, stirring and dissolving;Water soluble collagen 0.6g, mixing is added in the completely backward system of dissolution Uniformly bubble removing is vacuumized up to premixed solution;
3, the moulding of micropin film, molding: premixed solution is disposably poured into special micropin mold, is vacuumized, drying is dry It is dry;
4, demould, encapsulate, sterilizing: removing demoulds up to soluble micropin film, cuts, and encapsulation finally carries out irradiation sterilization.
Embodiment 3:
The soluble micropin film major function of the present embodiment is whitening, moisturizing, promotees reparation and antibacterial, and specific preparation process is as follows:
1, the preparation of micropin mold: using wavelength for the laser micro-machining system of 355nm purple light, contains groove structure special PDMS mold on carry out Laser Micro-Machining, the micropin mold needle point of acquisition is cone shape, and the length of needle point is 200 μm, The base diameter of needle point is 600 μm, and the spacing between needle point is 700 μm, and the number of per square centimeter on average micropin needle point is about It is 100;
2, the preparation of premixed solution: by macromolecule Sodium Hyaluronate 1g, small-molecular-weight Sodium Hyaluronate 10g, chitosan hydrochloric acid Salt 3g and purified water 85.0g mixing, stirring and dissolving;Rice bran stoste 0.8g, arbutin 0.2g is added in the completely backward system of dissolution It is uniformly mixed and vacuumizes bubble removing up to premixed solution;
3, the moulding of micropin film, molding: premixed solution is disposably poured into special micropin mold, is vacuumized, drying is dry It is dry;
4, demould, encapsulate, sterilizing: removing demoulds up to soluble micropin film, cuts, and encapsulation finally carries out irradiation sterilization.
Embodiment 4:
The morphologic observation of 4.1 films and hardness determination
The micropin film of preparation is placed under 40 times of optical microscopies, micropin form is observed, is shown in Table 1;And use texture Instrument detects the micropin intensity in different embodiments, the results are shown in Table 1.
Cell toxicity test
Cell toxicity test is carried out according to method as defined in GB/T16886.5~2003 (contact method), is shown in Table 1.
1 Examples 1 to 3 form of table and performance detection
4.3 bacteriostatic test
Hybrid NC machine tool base plate is prepared first, picks them separately a little cultured staphylococcus aureus, green pus with oese Bacteria suspension is made in sterile saline 5ml in bacillus and Escherichia coli inclined-plane culture substratess.Bacteria suspension 1.0ml is taken to be added to In the culture dish of sterilizing-drying, addition is cooled to 50 DEG C or so of ordinary nutritional broth agar culture medium, shakes up, to abundant It is spare after condensation.Then bacteriostatic test is carried out, sample film is cut into the disk of 1.0cm, is affixed on Hybrid NC machine tool base plate, 35~37 DEG C of inversions are cultivated 20~24 hours, are observed bacterial growth situation, are shown in Table 2.
2 Examples 1 to 3 bacteriostatic experiment result of table
4.4 micropin film anti-aging effects
To 10 45-60 years old ages, have obvious crow's feet (wrinkle cannot intersect, and main wrinkle at least 2cm long) from It is willing to that the side crow's feet position of subject carries out treatment as treatment group using the micropin film of embodiment 2, other side crow's feet is not Clinical protocol as a control group is treated, half an hour is treated with micropin film sooner or later daily by treatment group, and control group is without controlling It treats, is measured using the crow's feet after two weeks to treatment group and control group, the crow's feet phase for the treatment of group is found after statistical analysis Control group is significantly shorter, control group crow's feet average length is 2.6, and control group is not into and the crow's feet for the treatment of group Crow's feet of the average length in 1.7 treatment groups.Illustrate that the soluble micropin of the invention patent has the anti-wrinkle anti-senescence function of skin.
Micropin film whitening effect
Skin color (skin etc. is measured according to Lab chrominance space as defined in international lighting association to 36 volunteer's skins Grade classification declaration: it is divided into I, II, III, IV, V totally five ranks from shallow to deep by skin), it, will after pressing skin color classification to subject Above-mentioned micropin film pressing removes after 4 hours in subject's face, daily using once, observes whitening effect after two weeks: discovery 36 Name subjects skin obtains certain whitening effect, and concrete outcome is shown in Table 3.
3 Examples 1 to 3 whitening effect of table
It should be understood that the foregoing is merely presently preferred embodiments of the present invention, it is not intended to limit the invention, it is all in the present invention Spirit and principle within, any modification, equivalent replacement, improvement and so on, should be included in protection scope of the present invention it It is interior.

Claims (8)

1. a kind of preparation method of solubility micropin film, which is characterized in that including following operating procedure:
A1) the preparation of micropin mold;
A2) the preparation of premixed solution;
A3) the molding of micropin film;
A4 it) demoulds, encapsulate, sterilizing.
2. a kind of soluble micropin film as described in claim 1, which is characterized in that
The premixed solution is by one of Sodium Hyaluronate, water soluble chitosan and other function component or a variety of forms;Institute Micropin mold is stated to be prepared by laser micro-machining system.
3. a kind of soluble micropin film as claimed in claim 2, which is characterized in that
The Sodium Hyaluronate is 10~100 kDa Sodium Hyaluronate of 500~2000 kDa of macromolecule and small-molecular-weight One or both of;
The water soluble chitosan is carboxymethyl chitosan, chitosan hydrochloride, chitosan quaternary ammonium salt, chitosan lactate, shell Glycan sulfuric ester, chitosan oligosaccharide, hyaluronic acid-like chitosan it is one or more;
The other function component be glycerol, pentanediol, hexylene glycol, water soluble collagen, epidermal growth factor, vitamin C, One of rice bran stoste, arbutin are a variety of.
4. a kind of soluble micropin film as claimed in claim 3, which is characterized in that the macromolecule Sodium Hyaluronate, small Molecular weight hyaluronic acid sodium, water soluble chitosan, other function component weight content be respectively 0~3%: 0~15% : 0~3%: 0~2%, remaining as the content of purified water.
5. a kind of preparation method of soluble micropin film as described in claim 1, which is characterized in that
The needle point of the micropin film is one of cone, triangular pyramidal, quadrangle taper, crescent;
The length of the micropin needle point is 10~3000 μm;
The base diameter of the micropin needle point is 50~1000 μm;
The spacing of the micropin needle point is 50~3000 μm.
6. a kind of preparation method of soluble micropin film as described in claim 1, which is characterized in that walked including following operation It is rapid:
A1) the preparation of micropin mold: using wavelength for the laser micro-machining system of 355nm purple light, in special groove structure mould Laser Micro-Machining is carried out on tool obtains micropin mold;
A2) the preparation of premixed solution: will be in macromolecule Sodium Hyaluronate, small-molecular-weight Sodium Hyaluronate, water soluble chitosan It is one or more mixed with purified water, stirring and dissolving;Other function component is added in the completely backward system of dissolution, as glycerol, One of pentanediol, hexylene glycol, water soluble collagen, epidermal growth factor, vitamin C, rice bran stoste or arbutin or It is a variety of, it is uniformly mixed and vacuumizes bubble removing up to premixed solution;
A3) the molding of micropin film: premixed solution is disposably coated in special micropin mold, vacuumizes by moulding, it is subsequent It is dry that vacuum environment is held in continuation of insurance;
A4) demould, encapsulate, sterilizing: removing demoulds up to soluble micropin film, cuts, and encapsulation finally carries out irradiation sterilization.
7. a kind of preparation method of soluble micropin film as described in claim 1 or 6, which is characterized in that
The side plate (1) of the micropin mold and microneedle array (2) distance are 5~50mm, micropin mold height is 10~ 100mm, micropin die width are 50~1000 mm;
The groove structure of the micropin mold includes crescent, rectangle, rectangular, diamond shape, circle, ellipse, and groove is high Degree is 5~50mm, 1~100 μm of groove inner surface horizontal departure;
The material of the micropin mold includes stainless steel material, polytetrafluoroethylene (PTFE), silica gel, PDMS.
8. a kind of solubility micropin film, which is characterized in that the soluble micropin film uses claim 1~7 any one The method is made.
CN201810598273.9A 2018-06-12 2018-06-12 Soluble microneedle film and preparation method thereof Active CN108969880B (en)

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CN110339474B (en) * 2019-07-19 2021-07-06 怡定兴科技股份有限公司 Needle base composition for microneedle patch and microneedle patch comprising same
CN110339474A (en) * 2019-07-19 2019-10-18 怡定兴科技股份有限公司 For microneedle patch needle bottom composition and include its microneedle patch
CN110664646A (en) * 2019-11-14 2020-01-10 广州新济薇娜生物科技有限公司 Composition with whitening effect, high-drug-loading-rate whitening soluble microneedle patch and preparation method thereof
CN110664646B (en) * 2019-11-14 2022-04-29 广州新济薇娜生物科技有限公司 Composition with whitening effect, high-drug-loading-rate whitening soluble microneedle patch and preparation method thereof
CN111084929A (en) * 2019-12-27 2020-05-01 广东工业大学 Antibacterial biological membrane composite microneedle and application thereof
CN110917489A (en) * 2019-12-27 2020-03-27 广东工业大学 Antibacterial chitosan microneedle and application thereof
CN111450405A (en) * 2020-05-08 2020-07-28 无锡元旭生物技术有限公司 Rapid preparation method of soluble microneedle patch stock solution
CN112870089A (en) * 2021-02-05 2021-06-01 华东师范大学 Soluble hyaluronic acid mask with microneedle structure and preparation method thereof
CN114228054A (en) * 2021-12-14 2022-03-25 优微(珠海)生物科技有限公司 Microneedle mould and preparation method of microneedle patch
CN114228054B (en) * 2021-12-14 2022-08-16 优微(珠海)生物科技有限公司 Microneedle mould and preparation method of microneedle patch
CN115400341A (en) * 2022-08-30 2022-11-29 华中科技大学 Soluble polymer microneedle and preparation method thereof
CN115400341B (en) * 2022-08-30 2024-02-02 华中科技大学 Soluble polymer microneedle and preparation method thereof
CN116548205A (en) * 2023-04-24 2023-08-08 南京师范大学 Microneedle preparation, microneedle patch, and preparation methods and applications thereof
CN116548205B (en) * 2023-04-24 2024-02-13 南京师范大学 Microneedle preparation, microneedle patch, and preparation methods and applications thereof

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