CN110947088A - Eye-protecting combined patch and preparation method thereof - Google Patents
Eye-protecting combined patch and preparation method thereof Download PDFInfo
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- CN110947088A CN110947088A CN201911244515.5A CN201911244515A CN110947088A CN 110947088 A CN110947088 A CN 110947088A CN 201911244515 A CN201911244515 A CN 201911244515A CN 110947088 A CN110947088 A CN 110947088A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
-
- 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
-
- 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
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- 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
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0021—Intradermal administration, e.g. through microneedle arrays, needleless injectors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/10—Ophthalmic agents for accommodation disorders, e.g. myopia
-
- 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
Abstract
The invention relates to an eye-protecting combined patch and a preparation method thereof. The eye-protecting combined patch comprises a microneedle patch and a hydrogel patch; the microneedle patch consists of a microneedle body and a microneedle substrate layer, wherein the microneedle body is prepared from an active ingredient and a microneedle auxiliary material; the active ingredient is at least one of retinol acetate, lutein and lutein ester; the microneedle auxiliary material consists of a high molecular material and a water-soluble micromolecular compound; the hydrogel patch is prepared by attaching hydrogel to a patch substrate; the hydrogel is prepared from the following raw materials: glycerol, sodium polyacrylate, sodium hyaluronate, tartaric acid, aluminum glycinate, EDTA-2Na, lutein, retinol acetate and water. The eye-protecting combined patch has a good eye-protecting effect, and can effectively improve the eyesight of myopia patients.
Description
Technical Field
The invention belongs to the field of microneedles, and particularly relates to an eye-protecting combined patch and a preparation method thereof.
Background
Everyone wants to have a pair of clear and bright eyes with clear objects, but with the development of modern science and technology, the electronic products are updated, and the way of work and rest and the time of work and rest are changed, so that the eyesight of children, teenagers, the middle-aged and the elderly people is obviously reduced.
Year 2019, month 4, 29, the national health council held a routine news bulletin. The results of the 2018-year myopia investigation work of children and teenagers conducted by the organization of the ministry of education and finance of the national health and health committee are introduced, the investigation covers the kindergarten in 1033 and the primary and secondary schools in 3810 all the country, the total screening number is 111.74 ten thousand, including 6.92 ten thousand of children in the kindergarten (6 years old) and 104.92 ten thousand of primary and secondary school students in each grade segment. The investigation result shows that the general myopia incidence situation of children and teenagers in China is severe. In 2018, the total myopia rate of children and teenagers in China is 53.6%, wherein the myopia rate of pupils is 36.0%, the myopia rate of junior high school students is 71.6%, and the myopia rate of high school students is 81.0%. Meanwhile, the myopia problem at low age is prominent. The survey results show that the myopia rate rapidly increases with the increase of grades in primary schools and junior and middle schools, the primary schools increase from 15.7% of grades to 59.0% of grades in six years, the junior and middle schools increase from 64.9% of grades in first year to 77.0% of grades in first third year, and the primary schools and the junior and middle schools are key age stages for myopia prevention and control in China. Meanwhile, the problem of high myopia cannot be ignored. The proportion of high myopia (myopia degree higher than 600 degrees) of students in third-class is up to 21.9%, and high myopia is one of blindness-causing eye diseases, is easy to cause a series of serious complications and needs to cause high vigilance and attention. According to investigation, the related harm factors of myopia of students in China widely exist, 67% of students have outdoor activity time less than 2 hours every day, 29% of students have outdoor activity time less than 1 hour, 73% of students have sleep time not reaching standards every day, and bad eye using behaviors such as overlong eye using time in short distance and unscientific use of electronic products generally exist. The factors play a main role in the high myopia incidence, and are important influence factors for causing high myopia rate of children and juveniles in China.
The middle-aged and the elderly people with age, the metabolic capability of the organism is reduced, the vision is also reduced more and more, and the eye problems such as blurred vision, presbyopia and even macular degeneration cataract and the like occur.
The microneedle transdermal drug delivery technology is a novel drug delivery mode developed under the condition that the micro-electro-mechanical system processing technology and the transdermal penetration technology are increasingly mature. The micro-needle array has the advantages of small size, high strength, capability of accurately controlling the puncturing position and depth, painless puncture and the like, can be used for transdermal drug delivery of chemical drugs, proteins, vaccines and the like, and has great development prospect. Microneedle technology has been widely used not only in the biomedical and biomedical fields but also in the cosmetic field, and has been widely used in europe, the united states of america, japan, korea, and the like. The micro-needle has wide application in the field of beauty, can be used for body shaping and beauty and skin care, and has good effects on treating visual deterioration, protecting eyes, losing hair, repairing bubble marks and the like; in general, the application of microneedles in the aspect of beauty and body can be summarized as the following aspects: improving eyesight, protecting eyes, resisting skin aging, preventing and treating alopecia, reducing weight, treating acne, removing dead skin tissue, reducing local accumulation of fat, and relieving dry skin.
However, most of the microneedle products in the market use water-soluble microneedles, and the microneedles are used alone to directly penetrate into the stratum corneum of the skin, so that the water-soluble components are slowly dissolved and absorbed in the dermis, and the problems that the quantity of the loaded active components of the microneedles is too small and the use effect of the microneedles is affected due to the slow dissolution and absorption rate of the water-soluble microneedles are caused exist.
Disclosure of Invention
Based on the technical scheme, the eye protection combined patch has a good eye protection effect, has a good prevention and treatment effect on myopia of various ages, and can effectively improve the eyesight of myopia patients.
The specific technical scheme is as follows:
an eye-protecting combined patch comprises a microneedle patch and a hydrogel patch;
the microneedle patch consists of a microneedle body and a microneedle substrate layer, wherein the microneedle body is prepared from an active ingredient and a microneedle auxiliary material;
the active ingredient is at least one of retinol acetate, lutein and lutein ester;
the microneedle auxiliary material consists of a high molecular material and a water-soluble micromolecular compound; the high polymer material is selected from at least one of polyvinylpyrrolidone, sodium hyaluronate, hyaluronic acid, hydroxypropyl methyl cellulose, polyvinyl alcohol, hydroxypropyl cellulose, methyl cellulose, sodium alginate, gelatin, polyethylene glycol and hydroxyethyl starch; the water-soluble small molecular compound is selected from at least one of glucosamine, glucose, mannitol, glutamic acid, aspartic acid, sodium dihydrogen carbonate and sodium dihydrogen phosphate;
the hydrogel patch is prepared by attaching hydrogel to a patch substrate; the hydrogel is prepared from the following raw materials in parts by weight:
in some of these embodiments, the hydrogel patch is prepared by attaching a hydrogel to a water-repellent nonwoven fabric and covering the surface with a transparent textured film.
In some embodiments, the sodium hyaluronate has an average molecular weight of 3000-100000, the hyaluronic acid has an average molecular weight of 100000-300000, the hydroxypropyl methylcellulose has an average molecular weight of 164000-400000, the polyvinyl alcohol has an average molecular weight of 30000-200000, the methylcellulose has an average molecular weight of 10000-100000, the sodium alginate has an average molecular weight of 32000-250000, the gelatin has an average molecular weight of 15000-150000, and the polyethylene glycol has an average molecular weight of 900-7800.
In some embodiments, the hydrogel is prepared from the following raw materials in parts by weight:
in some of these embodiments, the polymeric material consists of polyvinylpyrrolidone and sodium hyaluronate; the water-soluble small molecular compound is mannitol.
In some embodiments, the polymer material is composed of sodium hyaluronate and polyvinylpyrrolidone in a mass ratio of 1: 1-3. Wherein the molecular weight of the sodium hyaluronate is preferably 4500-5500; the polyvinylpyrrolidone is preferably polyvinylpyrrolidone K90.
In some of these embodiments, the active ingredients are retinol acetate and lutein esters.
In some of the examples, the active ingredients are retinol acetate and lutein ester at a mass ratio of 1: 1-2.
In some embodiments, the mass ratio of the active ingredient to the microneedle adjuvant is 1: 2-12; the mass ratio of the high molecular material to the water-soluble small molecular compound is 1-10: 1.
In some embodiments, the mass ratio of the active ingredient to the microneedle adjuvant is 1: 6-8; the mass ratio of the high molecular material to the water-soluble small molecular compound is 5-7: 1.
In some embodiments, the microneedle body is prepared from the following raw materials in parts by weight:
in some embodiments, the microneedle body is prepared from the following raw materials in parts by weight:
in some of these embodiments, the microneedle substrate layer is prepared from adjuvant a and adjuvant B, the adjuvant a is selected from at least one of sodium hyaluronate, hyaluronic acid and collagen; the auxiliary material B is at least one selected from hydroxypropyl cellulose, hydroxypropyl methylcellulose, glycerol, polyvinylpyrrolidone, polyvinyl alcohol, methylcellulose, sodium alginate, gelatin, polyethylene glycol and hydroxyethyl starch. Wherein the molecular weight of the sodium hyaluronate is preferably 25-30W.
In some embodiments, the auxiliary material A is sodium hyaluronate, the auxiliary material B is hydroxypropyl cellulose, and the mass ratio of the auxiliary material A to the auxiliary material B is 1: 2-4.
In some embodiments, the height of the needle body of the microneedle is 200-.
The invention also provides a preparation method of the eye-protecting combined patch.
The specific technical scheme is as follows:
a preparation method of an eye-protecting combined patch comprises the following steps:
preparation of microneedle patch:
(1) dissolving the active ingredients and the microneedle accessories with water to obtain a needle body solution, then injecting the needle body solution into a microneedle female die, placing the microneedle female die in an environment of 0.4-0.6MPa for pressurizing for 3-8min to infuse the needle body solution into a needle point micropore, removing the redundant needle body solution, and drying;
(2) dissolving a material for preparing a microneedle substrate layer by using water to obtain a substrate layer solution, uniformly coating the substrate layer solution on the surface of the mould treated in the step (1), placing the mould in an environment of 0.12-0.2MPa, instantly pressurizing for 8-12s, drying, and demolding to obtain the microneedle patch;
preparation of hydrogel patch:
(a) adding the lutein, sodium polyacrylate, retinol acetate and aluminum glycinate into glycerol, and stirring until the components are uniformly dispersed to obtain an oil phase solution;
(b) adding the EDTA-2Na, the tartaric acid and the sodium hyaluronate into water, and stirring until the powder is completely dissolved to obtain a water phase solution;
(c) under the condition of stirring, adding the water phase solution into the oil phase solution, uniformly stirring, and vacuumizing to remove bubbles in the hydrogel to obtain hydrogel fluid;
(d) and attaching the hydrogel fluid to a patch substrate, drying the patch substrate in a rotary dryer, and continuously blowing the hydrogel fluid through compressed air subjected to drying and sterilizing filtration in the rotary dryer to obtain the hydrogel patch.
In some of these embodiments, the drying conditions in step (2) comprise: the relative humidity is 5-15%, and the temperature is 20-30 ℃.
The eye-protecting combined patch and the preparation method thereof have the advantages that:
the eye protection combined patch is formed by matching a microneedle patch and a hydrogel patch, wherein the microneedle patch selects ester-soluble retinol acetate, lutein ester or lutein as active ingredients, and selects a specific high molecular material and a water-soluble small molecular compound to form an auxiliary material of a microneedle body, so that the obtained microneedle patch has good biocompatibility, degradability and good hardness and mechanical strength, the hardness and flexibility of a microneedle can sufficiently penetrate through a skin natural barrier-stratum corneum, the stratum corneum can be effectively punctured to generate an active ingredient transportation micro-channel, an eye protection fat-soluble active ingredient is transferred to a real cortex, and meanwhile, the microneedle patch can be quickly dissolved in the skin, and the active ingredient in the microneedle patch can be quickly absorbed and transferred to an eye blood vessel through the micro-blood vessel, so that a good eye protection effect is achieved; in addition, the hydrogel patch is prepared by selecting fat-soluble retinol acetate and lutein as active ingredients and matching with specific auxiliary materials, and can obtain unexpected eye protection effect when being used together with the microneedle patch. When the micro-needle patch is used, the micro-needle patch is firstly attached to the lower eyelid to form the micropore channel for the active molecules to enter the dermis layer of the skin and quickly absorb the active molecules, and then the hydrogel patch is attached to the back of the micro-needle patch to enable the hydrogel patch to be attached to the lower eyelid and release the active ingredients, so that the effects of relieving eye fatigue and improving eyesight are achieved. The inventor finds that the effect of the microneedle patch and the hydrogel patch in matching use is far better than the eye protection effect of the microneedle patch and the hydrogel patch when the microneedle patch and the hydrogel patch are used independently, the eyesight of myopia patients can be effectively improved, the microneedle patch has a good prevention and treatment effect on myopia of various ages, and the microneedle patch can be used for relieving eye fatigue and improving eyesight.
Furthermore, the eye protection effect of the eye protection combined patch can be further improved through further optimization of the types and the dosage of the raw materials, and the prevention and treatment effect on myopia is better.
The eye-protecting combined patch of the invention solidifies fat-soluble eye-protecting active ingredients and improves the stability of the active ingredients in the product.
The preparation method of the eye-protecting combined patch is simple and quick in process, the preparation method of the hydrogel patch shortens more than half of the time compared with the conventional method, the conventional hydrogel preparation method adopts a natural airing mode at present, the drying can be completed within 24-48 hours, the drying mode of drying by compressed air through rotary sterilization and filtration is adopted, the drying can be completed within 6-12 hours, and the production efficiency is greatly improved.
Detailed Description
In order that the invention may be more readily understood, reference will now be made to the following more particular description of the invention, examples of which are set forth below. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. These embodiments are provided so that this disclosure will be thorough and complete.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.
The present invention will be described in further detail with reference to specific examples.
The room temperature in the following examples refers to a room temperature of 20 to 30 ℃.
Example 1
The present example provides an eye-protecting combined patch, which is composed of a microneedle patch and a hydrogel patch.
The microneedle patch comprises a microneedle body and a microneedle substrate layer, wherein the microneedle body is prepared from the following raw materials in parts by weight:
the microneedle substrate layer is prepared from the following raw materials in parts by weight:
5 portions of sodium hyaluronate (molecular weight is 28W)
15 portions of hydroxypropyl cellulose
80 parts of water.
The preparation method of the microneedle patch comprises the following steps:
(1) dissolving lutein, sodium hyaluronate (molecular weight of 5000), polyvinylpyrrolidone K90 and mannitol with water to obtain needle solution, injecting the needle solution into a 100 × 100 PDMS female mold, placing the whole mold in an environment of 0.5MPa, pressurizing for 5min, injecting the needle solution into needle point micropores, removing the redundant needle solution, and drying the mold in a dryer (relative humidity of 10%) at room temperature for 2 h.
(2) Dissolving sodium hyaluronate and hydroxypropyl cellulose in water to obtain a basal layer solution, uniformly coating the basal layer solution on the surface of the mould treated in the step (1), quickly placing the whole mould in an environment of 0.2MPa, instantly pressurizing for 10s, taking out the mould, quickly placing the mould in a dryer (with the relative humidity of 10%), drying at room temperature for 6 hours, and demolding to obtain the microneedle patch.
The hydrogel patch is prepared from the following raw materials in parts by weight:
the preparation method of the hydrogel patch comprises the following steps:
(1) adding lutein, sodium polyacrylate, retinol acetate and aluminum glycinate into glycerol, and stirring to disperse uniformly to obtain oil phase solution for use;
(2) adding EDTA-2Na, tartaric acid and sodium hyaluronate (molecular weight is 28W) into water, and stirring until the powder is completely dissolved to obtain an aqueous solution for later use;
(3) adding the water phase solution into the oil phase solution under the condition of stirring, starting vacuum after uniformly stirring, keeping the vacuum degree at-0.1 MPa, and extracting bubbles in the hydrogel to obtain transparent to semitransparent hydrogel fluid;
(4) uniformly coating the obtained hydrogel fluid on water-repellent non-woven fabric, covering with transparent mesh film, placing in a rotary dryer, continuously drying the hydrogel patch in the rotary dryer with compressed air subjected to drying and sterilizing filtration for 6.5 hours, and cutting into specific patch shape.
Example 2
The present example provides an eye-protecting combined patch, which is composed of a microneedle patch and a hydrogel patch.
The microneedle patch comprises a microneedle body and a microneedle substrate layer, wherein the microneedle body is prepared from the following raw materials in parts by weight:
the microneedle substrate layer is prepared from the following raw materials in parts by weight:
5 portions of sodium hyaluronate (molecular weight is 28W)
15 portions of hydroxypropyl cellulose
80 parts of water.
The preparation method of the microneedle patch comprises the following steps:
(1) dissolving lutein, retinol acetate, sodium hyaluronate (molecular weight of 5000), polyvinylpyrrolidone K90 and mannitol in water to obtain needle solution, injecting the needle solution into a 100 × 100 PDMS female mold, placing the whole mold in an environment of 0.5MPa, pressurizing for 5min, injecting the needle solution into needle micropores, removing the redundant needle solution, and placing the whole mold in a dryer (relative humidity of 10%) for drying at room temperature for 2 h.
(2) Dissolving sodium hyaluronate (molecular weight of 28W) and hydroxypropyl cellulose in water to obtain a basal layer solution, uniformly coating the basal layer solution on the surface of the mould treated in the step (1), quickly placing the whole mould in an environment of 0.2MPa, instantly pressurizing for 10s, taking out the mould, quickly placing the mould in a dryer (relative humidity of 10%), drying at room temperature for 6 hours, and demolding to obtain the microneedle patch.
The hydrogel patch is prepared from the following raw materials in parts by weight:
the preparation method of the hydrogel patch comprises the following steps:
(1) adding lutein, sodium polyacrylate, retinol acetate and aluminum glycinate into glycerol, and stirring to disperse uniformly to obtain oil phase solution for use;
(2) adding EDTA-2Na, tartaric acid and sodium hyaluronate (molecular weight is 28W) into water, and stirring until the powder is completely dissolved to obtain an aqueous solution for later use;
(3) adding the water phase solution into the oil phase solution under the condition of stirring, starting vacuum after uniformly stirring, keeping the vacuum degree at-0.1 MPa, and extracting bubbles in the hydrogel to obtain transparent to semitransparent hydrogel fluid;
(4) uniformly coating the obtained hydrogel fluid on water-repellent non-woven fabric, covering with transparent mesh film, placing in a rotary dryer, continuously drying the hydrogel patch in the rotary dryer with compressed air subjected to drying and sterilizing filtration for 6.5 hours, and cutting into specific patch shape.
Example 3
The present example provides an eye-protecting combined patch, which is composed of a microneedle patch and a hydrogel patch.
The microneedle patch comprises a microneedle body and a microneedle substrate layer, wherein the microneedle body is prepared from the following raw materials in parts by weight:
the microneedle substrate layer is prepared from the following raw materials in parts by weight:
5 portions of sodium hyaluronate (molecular weight is 28W)
15 portions of hydroxypropyl cellulose
80 parts of water.
The preparation method of the microneedle patch comprises the following steps:
(1) dissolving lutein ester, retinol acetate, sodium hyaluronate (molecular weight of 5000), polyvinylpyrrolidone and mannitol with water to obtain needle body solution, injecting the needle body solution into a PDMS female mold with 100 x 100, placing the whole mold in an environment of 0.5MPa, pressurizing for 5min, injecting the needle body solution into needle point micropores, removing the redundant needle body solution, and placing the whole mold in a dryer (relative humidity of 10%) to dry at room temperature for 2 h.
(2) Dissolving sodium hyaluronate (molecular weight of 28W) and hydroxypropyl cellulose in water to obtain a basal layer solution, uniformly coating the basal layer solution on the surface of the mould treated in the step (1), quickly placing the whole mould in an environment of 0.2MPa, instantly pressurizing for 10s, taking out the mould, quickly placing the mould in a dryer (relative humidity of 10%), drying at room temperature for 6 hours, and demolding to obtain the microneedle patch.
The hydrogel patch is prepared from the following raw materials in parts by weight:
the preparation method of the hydrogel patch comprises the following steps:
(1) adding lutein, sodium polyacrylate, retinol acetate and aluminum glycinate into glycerol, and stirring to disperse uniformly to obtain oil phase solution for use;
(2) adding EDTA-2Na, tartaric acid and sodium hyaluronate (molecular weight is 28W) into water, and stirring until the powder is completely dissolved to obtain an aqueous solution for later use;
(3) adding the water phase solution into the oil phase solution under the condition of stirring, starting vacuum after uniformly stirring, keeping the vacuum degree at-0.1 MPa, and extracting bubbles in the hydrogel to obtain transparent to semitransparent hydrogel fluid;
(4) uniformly coating the obtained hydrogel fluid on water-repellent non-woven fabric, covering with transparent mesh film, placing in a rotary dryer, continuously drying the hydrogel patch in the rotary dryer with compressed air subjected to drying and sterilizing filtration for 6.5 hours, and cutting into specific patch shape.
Example 4 mechanical Strength testing of microneedles
This example tests the mechanical strength of microneedle patches prepared in examples 1-3.
The method comprises the following steps: and taking out the prepared microneedle sample, exposing the microneedle sample in the air for about 2min, and shearing off the protrusions around the microneedle by using scissors after the microneedle is softened, so that the microneedle is flat and flat, the test is convenient, and the error is reduced. The microneedle tip was placed up on the test platform and an axial vertical force was applied using a P/6 type flat head stainless steel cylindrical probe at a steady speed of 0.1mm/sec with an excitation force of 0.05N. The test software is opened, and the parameters are selected: the probe descending speed is 0.1mm/s, the probe compression speed is 0.1mm/s, the probe lifting speed is 0.1mm/s, the compression amount is 90%, the trigger force is 5g, the data acquisition rate is 200pps, and the mechanical change of the probe contacting with the needle point until the preset height (the microneedle height is 800 mu m) is reached is recorded by the analyzer. After the test is finished, taking out the tested microneedle sample on the carrying platform, and observing the local morphological change of the microneedle after the acting force of the probe of the texture analyzer by using a digital microscope.
The results are shown in Table 1.
| Serial number | Group of | hardness/N | Extension distance/mm |
| 1 | Example 1 microneedle patch | 4.83±0.15 | 0.365±0.03 |
| 2 | Example 2 microneedle patch | 4.68±0.17 | 0.379±0.03 |
| 3 | Example 3 microneedle patch | 4.81±0.18 | 0.367±0.04 |
| 4 | Aonis hyaluronic acid micro-needle eye paste | 2.81±0.15 | 0.48±0.05 |
As can be seen from the data in the table, the microneedle patches of examples 1 to 3 had very good mechanical strength and hardness about 2N higher than that of the Aunies hyaluronic acid microneedle eye patch.
Example 5 dissolution and absorption Rate comparative experiments
The microneedle patches obtained in examples 1 to 3 were used alone, respectively, as a control group, an anis hyaluronic acid microneedle eye patch, and the dissolution rate and absorption rate of microneedles were examined, and a white rat was used as an experimental animal model. Shaving hair on the back of a rat, respectively and independently sticking microneedle patches on the back of the rat, observing the time required for completely dissolving the microneedles of each group, and extracting blood from the tail vein of the rat after dissolving to determine the content of the active ingredients.
After dissolving the microneedle patch of each group, 0.5ml of blood of the tail vein of the great white rat is respectively extracted by a sterile syringe and stored at the temperature of minus 20 ℃ to be detected. Example 1 blood samples of microneedle patch group were tested for lutein content, blood samples of microneedle patch group of example 2 were tested for lutein content, and blood samples of microneedle patch group of example 3 were tested for lutein ester (as lutein) content.
The method for measuring the content of the lutein is as follows:
the measurement is carried out by high performance liquid chromatography (0512 of the fourth portion of the pharmacopoeia 2015 edition).
Chromatographic conditions and system applicability test: octadecylsilane chemically bonded silica was used as a filler (Kromasil-C18250X 4.6mm, 5 μm;); 100% acetonitrile is used as a mobile phase; the detection wavelength is 450nm, the flow rate is 0.8ml/min, and the column temperature is 25 ℃. Weighing 10mg of lutein reference substance, placing the lutein reference substance in a 100ml measuring flask, dissolving the lutein reference substance by using absolute ethyl alcohol, diluting the lutein reference substance to a scale, shaking up, precisely transferring 1ml to 10ml measuring flask, fixing the volume by using absolute ethyl alcohol to the scale, shaking up to obtain a system applicability solution, injecting 5 mu l of the system applicability solution into a liquid chromatograph, recording a chromatogram, and calculating the number of theoretical plates according to the lutein peak to be not less than 3000.
Preparation of control solutions: taking a proper amount of lutein reference substance, precisely weighing, adding water to dissolve, and quantitatively diluting to obtain a solution containing 0.1mg of lutein per lmL.
Preparation of a test solution: respectively weighing 0.1g of each of the white mouse blood samples obtained from the serial numbers 1-3, placing the white mouse blood samples into a 25ml measuring flask, adding absolute ethyl alcohol to dissolve the white mouse blood samples and fixing the volume to a scale, shaking up the white mouse blood samples, centrifuging the white mouse blood samples at 10000rpm for 3 minutes, filtering the white mouse blood samples, and taking the subsequent filtrate as a sample solution.
The determination method comprises the following steps: precisely measuring 5 μ l of each of the reference solution and the sample solution, respectively injecting into a liquid chromatograph, recording chromatogram, and calculating according to external standard method by peak area.
Calculating the formula: (1)
in the formula: f is a correction factor for lutein;
CcontrolThe concentration of lutein (mg/ml) in the control solution;
AcontrolIs the peak area of lutein in the control solution.
(2)
In the formula: f. ofAverageAn average correction factor for lutein;
Asample (A)Is the peak area of the main peak in the test solution;
VbodyIs the volume (ml) of the test sample;
and m is the sample weighing amount of the test sample.
The results are shown in table 2:
table 2 experimental results of dissolution and absorption of microneedle patch
| Serial number | Group of | Time required for dissolution | Content of active ingredients in blood |
| 1 | Example 1 microneedle patch | 35 minutes | 52ng/L |
| 2 | Example 2 microneedle patch | 32 minutes | 55ng/L |
| 3 | Example 3 microneedle patch | 30 minutes | 60ng/L |
| 4 | Aonis hyaluronic acid micro-needle eye paste | 60 minutes | N/A |
By comparison, it can be found that the microneedle patches prepared in examples 1 to 3 have a dissolution rate and an absorption rate of the active ingredient, which are much better than those of commercially available oeniss hyaluronic acid microneedle eye patches.
Example 6 stability comparative experiment
The microneedle patch and the hydrogel patch obtained in examples 1 to 3, and the control group's pearl eye drops and lutein eye patch were placed in a 45 ℃ stability test chamber, and the active substance content of each product was measured on 0 day, 10 days, 30 days, and 90 days, respectively. Example 1 microneedle patches, example 2 microneedle patches, example 1 hydrogel patches, example 2 hydrogel patches, example 3 hydrogel patches, lutein eye patches were tested for lutein content, example 3 microneedle patches were tested for lutein ester content (in terms of lutein), and pearl eye drops were tested for natural borneol content. The samples of each group are respectively placed in a stability test box at 45 ℃ on the basis of 100% of the content determination in 0 day, and are respectively sampled and determined in 0 day, 10 days, 30 days and 90 days, and the content of the samples is compared with the content of the samples in 0 day.
The xanthophyll content was measured in the same manner as in example 5 by high performance liquid chromatography (0512, the fourth guideline of the 2015 edition of Chinese pharmacopoeia).
The method for measuring the content of the natural borneol comprises the following steps: measured according to gas chromatography (appendix VI E of 2010 version of the Chinese pharmacopoeia).
Chromatographic conditions and system applicability test: using polyethylene glycol 20000(PEG-20M) as stationary phase, and coating concentration is 10%; temperature programming: the initial temperature was 140 ℃ and held for 12 minutes; the temperature was raised to 170 ℃ at a rate of 10 ℃ per minute and held for 10 minutes. The number of theoretical plates is not less than 1900 according to the calculation of the dextroborneol peak.
And (3) determination of a correction factor: a proper amount of methyl salicylate was taken, and ethyl acetate was added to make a solution containing 1mg per 1ml as an internal standard solution. And another preferable borneol reference substance of 12.5mg is precisely weighed and placed in a 25ml measuring flask, the internal standard solution is used for dissolving and diluting to the scale, the mixture is shaken up, 2ul of the mixture is absorbed, and the mixture is injected into a gas chromatograph to calculate the correction factor.
And (3) determination: precisely weighing 5ml of the Zhenshiming eye drop, placing in a test tube with a plug, precisely adding 5ml of internal standard solution, shaking for extraction, standing for layering, collecting supernatant, sucking 2ul, injecting into a gas chromatograph, and measuring.
The results are shown in Table 3: the liposoluble active ingredients (lutein, lutein ester, retinol acetate) are solid-stated to be made into microneedle patch or hydrogel patch, which can greatly improve stability and prolong shelf life.
Table 3 stability test data of microneedle patch
Example 7 drying of hydrogel Patches comparative experiment
A batch of hydrogel sheets was prepared according to the composition of the hydrogel patch raw material of example 3, and was divided into 3 groups for drying, the first group was dried in a natural air-drying manner, the second group was dried in a heated air circulation box at 60 ℃, the third group was dried in a rotary dryer with compressed air through drying and sterilizing filtration (i.e., the drying manner of example 3), and the time required for completing the drying (the drying end point was that the transparent reticulated film on the hydrogel patch could be peeled off from the hydrogel and did not adhere to the hydrogel), the active ingredient content after drying, and the microorganism content after drying were examined, respectively.
The content of the active ingredient was determined by taking the content of lutein in the hydrogel sheet before drying as a 100% reference, and the lutein content of the hydrogel sheet after drying was measured and compared with the content before drying.
The xanthophyll content was measured in the same manner as in example 5 by high performance liquid chromatography (0512, the fourth guideline of the 2015 edition of Chinese pharmacopoeia).
The total bacteria count was determined as follows:
one, equipment and materials:
a constant-temperature incubator: 36 +/-1 ℃; constant temperature water bath: 55 +/-1 ℃ of temperature; balance: the sensory quantity is 0.1 g; homogenizer, alcohol burner, autoclave, graduated flask: 200 ml; a conical flask: capacity 250mL, 500 mL; sterilizing the culture dish: the diameter is 90 mm; sterilizing the graduated straw: 1ml, 10ml or micropipettes and tips.
II, culture medium and reagent:
lecithin tween 80-nutrient agar medium: weighing 51g of lecithin Tween 80-nutrient agar, adding 1000mL of distilled water or deionized water, stirring, heating, boiling to dissolve completely, packaging into conical flask, and autoclaving at 121 deg.C for 20 min.
Sterile physiological saline: weighing 8.5g of sodium chloride, dissolving in 1000mL of distilled water, subpackaging in conical flasks with stirrer, each flask containing 90mL of sodium chloride, and autoclaving at 121 deg.C for 20 min.
Sterilized Tween 80: collecting Tween 8050 ml, and autoclaving at 121 deg.C for 20 min.
Thirdly, experimental steps:
1. dilution of samples
Weighing 10g of hydrogel sample, adding into 90mL of sterilized normal saline, fully shaking and uniformly mixing to disperse and suspend the hydrogel sample, standing, and taking supernatant as a detection solution with a ratio of 1: 10.
2. Manipulation and culture of samples
A sterile pipette is used to aspirate 1ml of 1:10 of test solution and inject the solution into a 9ml sterile physiological saline test tube to prepare a 10-fold serial dilution sample. Each incremental dilution was replaced with 1mL sterile pipette or tip. Respectively injecting 1mL of 2-3 sample homogeneous solutions with proper dilution into a sterilization plate, respectively injecting 2 plates for each dilution, pouring lecithin and Tween 80-nutrient agar culture medium which is melted and cooled to 45-50 ℃ into the plates, wherein each plate is about 15mL, immediately rotating the plates to fully and uniformly mix the samples and the culture medium, turning the plates after the agar is solidified, and culturing for 48 +/-2 h in an incubator at 36 +/-1 ℃. And adding about 15mL of lecithin and Tween 80-nutrient agar culture medium into another sterile empty plate without the sample, turning the plate after the agar is solidified, and culturing in an incubator at 36 +/-1 ℃ for 48 +/-2 h to serve as a blank control.
3. Colony counting method
The number of colonies is counted by visual observation, and then the colonies are checked by a magnifying glass with the magnification of 5-10 times to prevent omission. After counting the number of colonies on each plate, the average number of colonies grown on each plate at the same dilution was determined. If the plate contains colonies which are connected into a sheet shape or colonies which are flower-like spread, the plate is not suitable for counting. If the number of plate-shaped colonies is less than half of the number of colonies in the plate, and the number of colonies in the other half is uniformly distributed, the number of colonies in the half plate can be counted and multiplied by 2 to represent the number of colonies in the whole plate.
The results are shown in Table 4: the drying mode that adopts rotary dryer to be equipped with through drying and aseptic filterable compressed air and weather can accelerate the drying rate of aquogel paster, can keep active ingredient not to be heated simultaneously and decompose and prevent that the bacterium from breeding.
TABLE 4 Effect of drying Pattern on hydrogel Patches
| Group of | Naturally drying in the air | Hot air circulating windCase 60 deg.C | Rotary dryer |
| Active ingredient content before drying | 100％ | 100％ | 100％ |
| Content of active ingredient after drying | 99.6％ | 95.6％ | 99.8％ |
| Total number of bacteria before drying | 1cfu/g | 1cfu/g | 1cfu/g |
| Total number of bacteria after drying | 100cfu/g | 3cfu/g | 2cfu/g |
| Time required for drying | 42 hours | 6 hours | 6.5 hours |
Example 8 Effect experiment for improving eyesight
Randomly extracting 140 patients suffering from myopia at the ages of 10-60, wherein the myopia degree is 100-; the first group was the eye-protecting combined patch of example 3, which was used once in the morning and evening for 60 minutes, the second group was the microneedle patch of example 3, which was used once in the morning and evening for 60 minutes, the third group was the hydrogel patch of example 3, which was used once in the morning and evening for 60 minutes, the fourth group was the lutein patch, which was used once in the morning and evening for 60 minutes, the fifth group was the microneedle patch of example 3 and the lutein patch, which were used once in the morning and evening for 60 minutes, the sixth group was the rare eyesight eye drops, which was used once in the morning and evening, and the seventh group was the microneedle patch and the rare eyesight eye drops of example 3, which were used once in the morning and evening for 60 minutes, and the degree of myopia decline of 7 groups of patients after 1 month and 2 months of use of each product was examined.
The microneedle patch of example 3 was used as follows: after the eyelids were cleaned with water and wiped dry, 2 microneedle patches were applied to the eyelid areas of both eyes, and gently pressed for 60 minutes and then removed, once in the morning and evening.
The hydrogel patch of example 3 was used as follows: after the eyelids were cleaned with water and wiped dry, 2 pieces of hydrogel patches were applied to the eyelid areas of both eyes, and gently pressed, and taken down after 60 minutes, once in the morning and evening.
The eye-protecting combination patch of example 3 was used as follows: cleaning eyelid with water, wiping to dry, applying 2 pieces of microneedle patch to eyelid parts of two eyes, pressing gently, applying 2 pieces of hydrogel patch to eyelid parts of two eyes (applying on the microneedle patch), pressing gently, and taking down after 60 min, wherein the application is performed once in the morning and at night.
The application method of the lutein patch comprises the following steps: cleaning eyelid with water, wiping to dry, applying 2 pieces of xanthophyll patch to eyelid parts of two eyes, pressing gently, and taking down after 60 min, once in the morning and evening.
The method for using the microneedle patch and the lutein patch of example 3 together is as follows: cleaning eyelid with water, wiping, applying 2 microneedle patches to eyelid parts of two eyes, pressing gently, applying 2 lutein eye patches to eyelid parts of two eyes (on the microneedle patches), pressing gently, and taking down after 60 min, wherein the two patches are applied respectively in the morning and evening
The application method of the Zhenshiming eye drops comprises the following steps: dripping the Zhenshiming eye drop 2 into the eye once in the morning and at night.
The method of using the microneedle patch of example 3 together with the pearl eye drops is as follows: cleaning eyelid with water, wiping to dry, applying 2 pieces of microneedle patch to eyelid of two eyes, pressing gently, applying 2 drops of Zhenshiming eye drop to eye, and removing microneedle patch after 60 min.
The results are shown in Table 5: the eye-protecting combined patch of the embodiment 3 has a remarkable eyesight improving effect, and the eyesight improving effect is obviously better than that of a microneedle patch and a hydrogel patch which are used independently, and is better than that of the microneedle patch of the embodiment 3 and a commercially available product.
TABLE 5 Effect of the eye-protecting combined patch of the present invention on treating myopia
The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (10)
1. An eye-protecting combined patch is characterized by comprising a microneedle patch and a hydrogel patch;
the microneedle patch consists of a microneedle body and a microneedle substrate layer, wherein the microneedle body is prepared from an active ingredient and a microneedle auxiliary material;
the active ingredient is at least one of retinol acetate, lutein and lutein ester;
the microneedle auxiliary material consists of a high molecular material and a water-soluble micromolecular compound; the high polymer material is selected from at least one of polyvinylpyrrolidone, sodium hyaluronate, hyaluronic acid, hydroxypropyl methyl cellulose, polyvinyl alcohol, hydroxypropyl cellulose, methyl cellulose, sodium alginate, gelatin, polyethylene glycol and hydroxyethyl starch; the water-soluble small molecular compound is selected from at least one of glucosamine, glucose, mannitol, glutamic acid, aspartic acid, sodium dihydrogen carbonate and sodium dihydrogen phosphate;
the hydrogel patch is prepared by attaching hydrogel to a patch substrate; the hydrogel is prepared from the following raw materials in parts by weight:
2. an eye-protecting combined patch according to claim 1, wherein the hydrogel is prepared from raw materials comprising, in parts by weight:
3. an eye-protecting combination patch according to claim 1, wherein the polymeric material is comprised of polyvinylpyrrolidone and sodium hyaluronate; the water-soluble small molecular compound is mannitol.
4. An eye-protecting combination patch according to claim 1, wherein the active ingredients are retinol acetate and lutein ester.
5. An eye-protecting combined patch according to any one of claims 1-4, wherein the polymeric material consists of sodium hyaluronate and polyvinylpyrrolidone in a mass ratio of 1: 1-3; and/or the presence of a catalyst in the reaction mixture,
the active ingredients are retinol acetate and lutein ester with the mass ratio of 1: 1-2.
6. An eye-protecting combined patch according to any one of claims 1-4, wherein the mass ratio of the active ingredient to the microneedle adjuvant is 1: 2-12; the mass ratio of the high molecular material to the water-soluble small molecular compound is 1-10: 1.
7. The eye-protecting combined patch as claimed in claim 6, wherein the mass ratio of the active ingredient to the microneedle adjuvant is 1: 6-8; the mass ratio of the high molecular material to the water-soluble small molecular compound is 5-7: 1.
8. An eye-protecting combined patch according to any one of claims 1-4, wherein the microneedle body is prepared from raw materials comprising the following components in parts by weight:
9. an eye-protecting combined patch according to any one of claims 1-4, wherein the microneedle substrate layer is prepared from adjuvant A and adjuvant B, wherein the adjuvant A is at least one selected from the group consisting of sodium hyaluronate, hyaluronic acid and collagen; the auxiliary material B is at least one selected from hydroxypropyl cellulose, hydroxypropyl methylcellulose, glycerol, polyvinylpyrrolidone, polyvinyl alcohol, methylcellulose, sodium alginate, gelatin, polyethylene glycol and hydroxyethyl starch.
10. A method for preparing an eye-protecting combined patch according to any one of claims 1-9, which comprises the steps of preparing a microneedle patch and preparing a hydrogel patch, wherein the preparation of the microneedle patch comprises the following steps:
(1) dissolving the active ingredients and the microneedle accessories with water to obtain a needle body solution, then injecting the needle body solution into a microneedle female die, placing the microneedle female die in an environment of 0.4-0.6MPa for pressurizing for 3-8min to infuse the needle body solution into a needle point micropore, removing the redundant needle body solution, and drying;
(2) dissolving a material for preparing a microneedle substrate layer by using water to obtain a substrate layer solution, uniformly coating the substrate layer solution on the surface of the mould treated in the step (1), placing the mould in an environment of 0.12-0.2MPa, instantly pressurizing for 8-12s, drying, and demolding to obtain the microneedle patch;
the preparation of the hydrogel patch comprises the following steps:
(a) adding the lutein, sodium polyacrylate, retinol acetate and aluminum glycinate into glycerol, and stirring until the components are uniformly dispersed to obtain an oil phase solution;
(b) adding the EDTA-2Na, the tartaric acid and the sodium hyaluronate into water, and stirring until the powder is completely dissolved to obtain a water phase solution;
(c) under the condition of stirring, adding the water phase solution into the oil phase solution, uniformly stirring, and vacuumizing to remove bubbles in the hydrogel to obtain hydrogel fluid;
(d) and attaching the hydrogel fluid to a patch substrate, drying the patch substrate in a rotary dryer, and continuously blowing the hydrogel fluid through compressed air subjected to drying and sterilizing filtration in the rotary dryer to obtain the hydrogel patch.
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| CN113813221A (en) * | 2021-10-29 | 2021-12-21 | 湖北省麦诗特生物科技有限公司 | Soluble beauty microneedle patch composition for removing wrinkles and resisting aging of skin and preparation method thereof |
| CN113876656A (en) * | 2021-10-29 | 2022-01-04 | 湖北省麦诗特生物科技有限公司 | Black eye and pouch removing soluble beautifying microneedle patch composition and preparation method thereof |
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