CN117653586A - Soluble microneedle and preparation method thereof - Google Patents

Soluble microneedle and preparation method thereof Download PDF

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Publication number
CN117653586A
CN117653586A CN202211064937.6A CN202211064937A CN117653586A CN 117653586 A CN117653586 A CN 117653586A CN 202211064937 A CN202211064937 A CN 202211064937A CN 117653586 A CN117653586 A CN 117653586A
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solution
microneedle
soluble
chitosan
soluble microneedle
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万昱
邓静怡
庄嘉琅
林素静
林宝茹
杨文龙
陈嘉
古晓曼
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Shenzhen Polytechnic
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Shenzhen Polytechnic
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    • 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
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • 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
    • 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
    • A61M2037/0053—Methods for producing microneedles

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Abstract

The embodiment of the invention discloses a soluble microneedle and a preparation method thereof. The preparation method comprises, for example: dialyzing the cross-linked framework aqueous solution by using a semipermeable membrane to obtain dialysate; adding the dialysate into a lubricant water solution and stirring to obtain a chitosan dilute solution; performing rotary evaporation drying treatment on the chitosan dilute solution to obtain a chitosan concentrated solution; adding the supporting material aqueous solution into the chitosan concentrated solution, stirring and centrifuging to obtain a soluble microneedle base solution; placing the soluble microneedle substrate solution into a microneedle female die, centrifuging and solidifying to obtain an initial soluble microneedle; and coating a backing skeleton solution onto the initial soluble microneedle and curing to obtain the soluble microneedle. The soluble microneedle provided by the embodiment of the invention has good mechanical property and drug release property in water, and the whole preparation process has the characteristics of high integration level, simplicity and rapidness in production, low cost, material saving and flexible processing.

Description

Soluble microneedle and preparation method thereof
Technical Field
The invention relates to the technical field of medicines. And more particularly, to a soluble microneedle based on a composite material and a method for preparing the same.
Background
At present, transdermal drug delivery technology is a research hotspot in biomedical technology and medical community. However, most transdermally administered drugs have low transmittance due to the natural barrier effect of the stratum corneum, and particularly water-soluble drugs or macromolecular drugs cannot permeate. The micro-needle transdermal administration is a minimally invasive administration mode integrating double advantages of injection administration and the traditional transdermal patch, and the micro-needle can assist the medicine to enter the skin through the stratum corneum, has the length insufficient for touching the subcutaneous pain nerve, and has the advantages of painless minimally invasive, safety and high skin permeability. The microneedles can be generally classified into solid microneedles, coated microneedles, hollow microneedles, and soluble microneedles, according to the mode of administration. Among them, soluble microneedles, which are made of biodegradable polymers, are receiving more and more attention and research, and drugs can be carried by the polymers and released as the polymers dissolve after the microneedles are inserted into the skin. The current preparation process of the soluble microneedle is complex, and in addition, the mechanical emphasis is insufficient due to the small size.
Disclosure of Invention
Aiming at least part of the defects and the defects in the prior art, the embodiment of the invention provides the soluble microneedle based on the composite material and the preparation method thereof, so that the preparation process of the soluble microneedle is simpler, and the prepared soluble microneedle has stronger mechanical strength.
In one aspect, a method for preparing a soluble microneedle provided by an embodiment of the present invention includes: mixing a polydimethylsiloxane curing agent and a prepolymer in a mass ratio of (0.5-3:5-20) in a vacuum environment to obtain a polydimethylsiloxane mixed solution, casting the polydimethylsiloxane mixed solution on a metal microneedle male die, and curing to obtain a microneedle female die; dialyzing the cross-linked skeleton aqueous solution by using a semipermeable membrane to obtain a dialysate, adding the dialysate into a lubricant aqueous solution, stirring to obtain a chitosan dilute solution, and performing rotary evaporation drying treatment on the chitosan dilute solution to obtain a chitosan concentrated solution; wherein the mass percentage range of the cross-linked skeleton in the cross-linked skeleton aqueous solution is 1% -3%, and the mass percentage range of the lubricant in the lubricant aqueous solution is 4% -8%; the temperature range of the rotary steaming drying treatment is 40-70 ℃ and the drying time is 0.5-3h; adding the supporting material aqueous solution into the chitosan concentrated solution, stirring and centrifuging to obtain a soluble microneedle base solution; wherein the mass percentage range of the supporting material in the supporting material aqueous solution is 10% -30%; placing the soluble microneedle substrate solution into the microneedle female die for centrifugation and solidification treatment to obtain an initial soluble microneedle; coating a backing skeleton solution on the initial soluble micro-needle for curing and demolding to obtain the soluble micro-needle; wherein the mass percentage range of the backing skeleton in the backing skeleton solution is 30-50%.
In another aspect, a method for preparing a soluble microneedle provided by an embodiment of the present invention includes: dialyzing the cross-linked framework aqueous solution by using a semipermeable membrane to obtain dialysate; adding the dialysate into a lubricant water solution and stirring to obtain a chitosan dilute solution; performing rotary evaporation drying treatment on the chitosan dilute solution to obtain a chitosan concentrated solution; adding the supporting material aqueous solution into the chitosan concentrated solution, stirring and centrifuging to obtain a soluble microneedle base solution; placing the soluble microneedle substrate solution into a microneedle female die, centrifuging and solidifying to obtain an initial soluble microneedle; and coating a backing skeleton solution on the initial soluble micro-needle and curing to obtain the soluble micro-needle.
In one embodiment of the present invention, the cross-linked skeleton in the aqueous solution of cross-linked skeleton has a mass percentage ranging from 1% to 3%, the lubricant in the aqueous solution of lubricant has a mass percentage ranging from 4% to 8%, and the support material in the aqueous solution of support material has a mass percentage ranging from 10% to 30%.
In one embodiment of the present invention, the spin-evaporating and drying the dilute chitosan solution to obtain a concentrated chitosan solution is specifically: the dilute chitosan solution was stirred and dried under vacuum for 0.5-3 hours, at a pressure of 100Mbar and a temperature in the range of 40-70 ℃.
In one embodiment of the invention, the cross-linked backbone is chitosan; the lubricant is one or more of trehalose, starch and cellulose.
In one embodiment of the present invention, the support material is one or more of carboxymethyl cellulose, hexylene glycol, sorbitol, polyethylene glycol, sodium hyaluronate, polyvinylpyrrolidone, and polyvinyl alcohol.
In one embodiment of the invention, the backing skeleton is one or more of carbomer, methylcellulose, polyvinylpyrrolidone k60, WI-3 tyrosol-b-agent, silicone rubber.
In one embodiment of the present invention, the preparation method further comprises: and mixing a polydimethylsiloxane curing agent and a prepolymer in a mass ratio of (0.5-3:5-20) in a vacuum environment to obtain a polydimethylsiloxane mixed solution, and casting the polydimethylsiloxane mixed solution on a metal microneedle male mold and curing to obtain the microneedle female mold.
In yet another aspect, the embodiment of the present invention provides a soluble microneedle, for example, a soluble microneedle prepared by the preparation method according to any one of the foregoing methods.
In one embodiment of the present invention, the shape of the microneedle is conical, triangular pyramid or polygonal pyramid.
The technical scheme has the following advantages or beneficial effects: the whole preparation flow of the preparation method of the soluble microneedle provided by the embodiment of the invention has the characteristics of high integration level, simplicity and rapidness in production, low cost, material saving and flexible processing, and is suitable for wide popularization and use. In addition, the preparation method comprises the steps of preparing a chitosan dilute solution by preparing a cross-linked framework aqueous solution and a lubricant aqueous solution, performing rotary evaporation drying treatment on the chitosan dilute solution to obtain a chitosan concentrated solution, and adding a support material aqueous solution to obtain a soluble microneedle substrate solution, so that the prepared soluble microneedle has stronger mechanical strength and can penetrate the skin. In addition, it has better drug release effect and great advantage in administration
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for the description of the embodiments will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
Fig. 1 is a schematic flow chart of a preparation method of a soluble microneedle according to an embodiment of the present invention.
Fig. 2 is a schematic flow chart of another preparation method of a soluble microneedle according to an embodiment of the present invention.
Fig. 3 a-3 c are schematic views of the appearance of a composite soluble microneedle with 8% mass percent of support material, wherein fig. 3a is a schematic view of the appearance of the needle under a 4-fold objective, fig. 3b is a schematic view of the appearance of the needle under a 10-fold objective, and fig. 3c is a schematic view of the overall appearance of the microneedle.
Fig. 4 a-4 c are schematic views of the appearance of a composite soluble microneedle with 20% mass percent of the support material, wherein fig. 4a is a schematic view of the appearance of the needle under a 4-fold objective, fig. 4b is a schematic view of the appearance of the needle under a 10-fold objective, and fig. 4c is a schematic view of the overall appearance of the microneedle.
Fig. 5 is a schematic diagram showing the results of mechanical property test of soluble microneedles prepared by the preparation method provided in the embodiment of the present invention.
Fig. 6a is a schematic view showing the effect of the composite material according to the embodiment of the present invention after the soluble microneedle needles prick the pigskin.
FIG. 6b is a schematic representation of the effect of a pure cross-linked backbone microneedle after needle punching of pigskin.
FIG. 7 is a schematic diagram of the model drug release rate of a pure cross-linked matrix microneedle at different temperatures.
FIG. 8 is a schematic diagram of the model drug release rates of the composite soluble microneedle according to the embodiment of the present invention under different temperature conditions.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
It should be noted that the terms "first," "second," and "one end" and the like in the description and the claims of the present invention are used for distinguishing between similar objects and not necessarily for describing a particular sequential or chronological order. It is to be understood that the terms so used are interchangeable under appropriate circumstances such that the embodiments of the invention described herein are capable of operation in sequences other than those illustrated or otherwise described herein. Furthermore, the terms "comprises," "comprising," and "having," and any variations thereof, are intended to cover a non-exclusive inclusion, such that a process, system, article, or apparatus that comprises a list of steps or elements is not necessarily limited to those steps or elements expressly listed but may include other steps or elements not expressly listed or inherent to such process, article, or apparatus.
As shown in fig. 1, an embodiment of the present invention provides a method for preparing a soluble microneedle based on a composite material. The preparation method of the soluble microneedle comprises the following steps:
s10: dialyzing the cross-linked framework aqueous solution by using a semipermeable membrane to obtain dialysate;
s20: adding the dialysate into a lubricant water solution and stirring to obtain a chitosan dilute solution;
s30: performing rotary evaporation drying treatment on the chitosan dilute solution to obtain a chitosan concentrated solution;
s40: adding the supporting material aqueous solution into the chitosan concentrated solution, stirring and centrifuging to obtain a soluble microneedle base solution;
s50: placing the soluble microneedle substrate solution into a microneedle female die, centrifuging and solidifying to obtain an initial soluble microneedle; and
s60: and coating a backing skeleton solution on the initial soluble micro-needle and curing to obtain the soluble micro-needle.
The whole preparation flow of the preparation method provided by the embodiment of the invention has the characteristics of high integration level, simple and quick production, low cost, material saving and flexible processing. In addition, the preparation method comprises the steps of preparing a cross-linked skeleton aqueous solution and a lubricant aqueous solution to obtain a chitosan dilute solution, performing rotary evaporation drying treatment on the chitosan dilute solution to obtain a chitosan concentrated solution, and adding a support material aqueous solution to obtain a soluble microneedle substrate solution, so that the prepared soluble microneedle has good mechanical property and drug release property in water.
Specifically, the mass percentage of the cross-linked framework in the cross-linked framework aqueous solution ranges from 1% to 3%. The mass percentage range of the lubricant in the aqueous solution of the lubricant is 4-8%, and the mass percentage range of the supporting material in the aqueous solution of the supporting material is 10-30%.
Wherein the cross-linked backbone is, for example, chitosan, in particular, e.g. chitosan. The lubricant is one or more of trehalose, starch and cellulose.
The support material is one or more of carboxymethyl cellulose, hexanediol, sorbitol, polyethylene glycol, sodium hyaluronate, polyvinylpyrrolidone and polyvinyl alcohol.
The backing skeleton is one or more of carbomer, methylcellulose, polyvinylpyrrolidone k60, WI-3 tyrosol-bolone, and silicone rubber.
In addition, in step S30, the spin-drying process specifically includes: the method for preparing the chitosan concentrated solution by carrying out spin evaporation drying treatment on the chitosan dilute solution comprises the following steps:
the dilute chitosan solution was stirred and dried under vacuum for 0.5-3 hours, at a pressure of 100Mbar and a temperature in the range of 40-70 ℃.
Further, step S50 specifically includes:
and placing the soluble microneedle substrate solution into the microneedle female die, centrifuging, scraping off redundant soluble microneedle substrate solution on the microneedle female die, and solidifying at the temperature of 40-70 ℃ for 0.5-2 hours to obtain the initial soluble microneedle.
In addition, step S60 specifically includes:
the backing matrix solution is applied to the initial soluble microneedles and cured at a temperature of 40-70 ℃ for 0.5-2 hours, and then the microneedle negative is peeled off to obtain the soluble microneedles.
Furthermore, as shown in fig. 2, the preparation method of the soluble microneedle provided by the embodiment of the invention may further include a preparation step of a female microneedle mould, specifically:
s70: and mixing a polydimethylsiloxane curing agent and a prepolymer in a mass ratio of (0.5-3:5-20) in a vacuum environment to obtain a polydimethylsiloxane mixed solution, and casting the polydimethylsiloxane mixed solution on a metal microneedle male mold and curing to obtain the microneedle female mold. The polydimethylsiloxane curing agent here is an uncrosslinked cured polydimethylsiloxane curing agent, the prepolymer being, for example, SYLGARD184 silicone rubber.
In addition, the mould of the microneedle female mould according to the embodiment of the invention has high transparency, and if the solution for preparing the soluble microneedle has color, after the solution is added into the micropores of the microneedle female mould, whether the solution permeates into the micropores of the mould is convenient to observe. In addition, the microneedle female die can be reused, so that the cost is reduced. After the soluble microneedle is stripped from the microneedle female mold, the microneedle female mold needs to be soaked in purified water for a period of time and then can be used. The female microneedle mould has strong flexibility and can prepare soluble microneedles with different heights according to the needs. The height of the microneedle negative mould is 1000-2000 μm, for example.
In addition, the soluble microneedle prepared by the preparation method of the soluble microneedle provided by the embodiment of the invention is prepared from two composite materials of a crosslinked framework material and a supporting material in a microneedle female die. The soluble microneedles are, for example, conical, triangular pyramid, polygonal pyramid, or other shaped pyramid.
In order to better understand the properties of the soluble microneedles prepared by the preparation method provided in the examples of the present invention, 3 specific test examples will be described below in comparison with pure crosslinked skeletal microneedles.
Test example 1 mechanical Property test of composite-based soluble microneedles
Sufficient mechanical strength is important for the microneedles to pierce the skin to create a tunnel for drug delivery. When preparing the soluble microneedle based on the composite material, as shown in fig. 3 a-3 c, when the mass percentage of the supporting material in the aqueous solution of the supporting material is 8%, the needle surface of the prepared soluble microneedle is flat, and the needle shape is very sharp. When the mass percentage of the supporting material in the supporting material aqueous solution is 10%, the surface of the needle body of the prepared soluble microneedle is very rugged, and the needle tip is also flexible. When the mass percentage of the supporting material in the supporting material aqueous solution is 20%, the needle surface of the soluble microneedle is greatly improved, and the needle tip becomes straight, as shown in fig. 4 a-4 c.
Furthermore, the composite material soluble microneedle based on 20% by mass of the supporting material is shrunken after drying, the length of the needle body is between 500 and 600 μm, and the length of the needle body of the pure cross-linked skeleton microneedle is between 700 and 800 μm. After mechanical property test by using weights, it was found that although the needle body was reduced due to shrinkage after drying due to the soluble microneedle of the composite material, the hardness was better than that of the pure crosslinked skeletal microneedle. As shown in FIG. 5, after weights of 50g and 200g are respectively pressed, the degree of change of the needle body height of the composite material soluble microneedle is obviously smaller than that of the needle body height of the pure cross-linked skeleton microneedle, so that the mechanical property of the soluble microneedle can be improved after the supporting material is added into the soluble microneedle.
Test example 2 microneedle penetration test of soluble microneedle based on composite material
To test the skin penetration ability of the composite dissolvable microneedles of the examples of the present invention, the human skin was replaced with pigskin. As shown in fig. 6a and 6b, both the pure cross-linked skeleton microneedle and the soluble microneedle based on the composite material can be pricked into the pigskin, but the pricked pigskin trace is shallow because the shrinkage of the soluble microneedle based on the composite material is large and the needle body length is short.
Test example 3 drug Release Capacity test of composite-based soluble microneedles
The test method comprises the following steps: rhodamine B is taken as a model drug, after the soluble microneedle is researched to be loaded with the rhodamine B, the rhodamine B is dissolved in an aqueous solution, and the drug release capacity of the pure cross-linked skeleton microneedle and the soluble microneedle based on the composite material is evaluated by measuring the content of the rhodamine B in the aqueous solution. As shown in fig. 7, the pure cross-linked matrix microneedles swelled within the first 15 minutes, and slowly dissolved after about 15 minutes. The pure crosslinked backbone microneedle took about 6 hours to dissolve completely at 37 ℃ and 12 hours at room temperature. As shown in fig. 8, the composite-based soluble microneedle was rapidly dissolved in about 20 minutes, and then slowly dissolved again, and completely dissolved after about 3 hours at 37 ℃ and 4 hours at normal temperature. Thus, the soluble microneedle based on the composite material can dissolve and release the drug in water, and the speed is faster than that of the pure crosslinked skeleton microneedle, and the sustained release drug delivery possibility can be realized in a very uniform and slow speed in the water-soluble process.
In summary, the whole preparation flow of the preparation method of the soluble microneedle provided by the embodiment of the invention has the characteristics of high integration level, simple and quick production, low cost, material saving and flexible processing, and is suitable for wide popularization and application. In addition, the preparation method comprises the steps of preparing a chitosan dilute solution by preparing a cross-linked framework aqueous solution and a lubricant aqueous solution, performing rotary evaporation drying treatment on the chitosan dilute solution to obtain a chitosan concentrated solution, and adding a support material aqueous solution to obtain a soluble microneedle substrate solution, so that the prepared soluble microneedle has stronger mechanical strength and can penetrate the skin. In addition, the medicine has better medicine release performance and great advantage in the administration aspect.
In addition, it should be understood that the foregoing embodiments are merely exemplary illustrations of the present invention, and the technical solutions of the embodiments may be arbitrarily combined and matched without conflict, fixed or contradiction of technical features and without departing from the purpose of the present invention.
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and are not limiting; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims (10)

1. A method of preparing a soluble microneedle comprising:
mixing a polydimethylsiloxane curing agent and a prepolymer in a mass ratio of (0.5-3:5-20) in a vacuum environment to obtain a polydimethylsiloxane mixed solution, casting the polydimethylsiloxane mixed solution on a metal microneedle male die, and curing to obtain a microneedle female die;
dialyzing the cross-linked skeleton aqueous solution by using a semipermeable membrane to obtain a dialysate, adding the dialysate into a lubricant aqueous solution, stirring to obtain a chitosan dilute solution, and performing rotary evaporation drying treatment on the chitosan dilute solution to obtain a chitosan concentrated solution; wherein the mass percentage range of the cross-linked skeleton in the cross-linked skeleton aqueous solution is 1% -3%, and the mass percentage range of the lubricant in the lubricant aqueous solution is 4% -8%; the temperature range of the spin-steaming drying treatment is 40-70, and the drying time is 0.5-3h.
Adding the supporting material aqueous solution into the chitosan concentrated solution, stirring and centrifuging to obtain a soluble microneedle base solution; wherein the mass percentage range of the supporting material in the supporting material aqueous solution is 10% -30%;
placing the soluble microneedle substrate solution into the microneedle female die for centrifugation and solidification treatment to obtain an initial soluble microneedle;
coating a backing skeleton solution on the initial soluble micro-needle to be cured and demoulded to obtain the soluble micro-needle; wherein the mass percentage range of the backing skeleton in the backing skeleton solution is 30-50%.
2. A method of preparing a soluble microneedle comprising:
dialyzing the cross-linked framework aqueous solution by using a semipermeable membrane to obtain dialysate;
adding the dialysate into a lubricant water solution and stirring to obtain a chitosan dilute solution;
performing rotary evaporation drying treatment on the chitosan dilute solution to obtain a chitosan concentrated solution;
adding the supporting material aqueous solution into the chitosan concentrated solution, stirring and centrifuging to obtain a soluble microneedle base solution;
placing the soluble microneedle substrate solution into a microneedle female die, centrifuging and solidifying to obtain an initial soluble microneedle;
and coating a backing skeleton solution on the initial soluble micro-needle and curing to obtain the soluble micro-needle.
3. The method according to claim 2, wherein the cross-linked skeleton in the aqueous solution of the cross-linked skeleton is in a mass percentage range of 1 to 3%, the lubricant in the aqueous solution of the lubricant is in a mass percentage range of 4 to 8%, and the supporting material in the aqueous solution of the supporting material is in a mass percentage range of 10 to 30%.
4. The preparation method according to claim 2, wherein the spin-evaporating and drying treatment of the chitosan dilute solution to obtain a chitosan concentrated solution comprises the following steps:
the dilute chitosan solution was stirred and dried under vacuum for 0.5-3 hours, at a pressure of 100Mbar and a temperature in the range of 40-70 ℃.
5. The method according to claim 2, wherein the crosslinked skeleton is chitosan; the lubricant is one or more of trehalose, starch and cellulose.
6. The method according to claim 2, wherein the support material is one or more of carboxymethyl cellulose, hexylene glycol, sorbitol, polyethylene glycol, sodium hyaluronate, polyvinylpyrrolidone, and polyvinyl alcohol.
7. The method of claim 2, wherein the backing skeleton is one or more of carbomer, methylcellulose, polyvinylpyrrolidone k60, WI-3 tyrosol-b mixture, silicone rubber.
8. The method of manufacturing according to claim 2, further comprising:
and mixing a polydimethylsiloxane curing agent and a prepolymer in a mass ratio of (0.5-3:5-20) in a vacuum environment to obtain a polydimethylsiloxane mixed solution, and casting the polydimethylsiloxane mixed solution on a metal microneedle male mold and curing to obtain the microneedle female mold.
9. A soluble microneedle, characterized in that the soluble microneedle is a soluble microneedle obtained by the preparation method according to any one of claims 1 to 8.
10. The soluble microneedle of claim 9, wherein the microneedle is conical, triangular pyramid or polygonal pyramid in shape.
CN202211064937.6A 2022-09-01 2022-09-01 Soluble microneedle and preparation method thereof Pending CN117653586A (en)

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