CN114010579A - Soluble anti-inflammatory repair microneedle and preparation method thereof - Google Patents
Soluble anti-inflammatory repair microneedle and preparation method thereof Download PDFInfo
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
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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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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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
- A61K47/30—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
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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
- A61K47/30—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
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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
- A61K47/30—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
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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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0046—Solid microneedles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0053—Methods for producing microneedles
Abstract
The invention relates to the technical field of skin repair, in particular to a soluble anti-inflammatory repair microneedle and a preparation method thereof. The microneedle comprises a needle body and a substrate; the needle body comprises a shaping material and an anti-inflammatory repairing composition; the anti-inflammatory repair composition comprises one or more of peptide repair compositions, mesenchymal stem cells and exosomes thereof, fibronectin, mussel mucin, cell growth factors, a tranquillizing anti-inflammatory component, and an antioxidant component. The preparation method comprises the following steps: preparing a needle body fluid, preparing a substrate, and preparing the microneedle. The microneedle contains the anti-inflammatory repairing composition, and when the needle body is prepared, the anti-inflammatory repairing composition and the excipient material are integrated and gradually released in the dissolving process of the excipient material; the micro-needle has a certain penetration depth, so that the anti-inflammatory repairing composition can be better absorbed when entering a patient, and the anti-inflammatory repairing effect is improved.
Description
Technical Field
The invention relates to the technical field of skin repair, in particular to a soluble anti-inflammatory repair microneedle and a preparation method thereof.
Background
With the increase of people's age and pressure, many adverse factors such as improper skin care habit, external pollution, too much working pressure, ultraviolet rays and the like can cause the skin to be damaged in different degrees, and phenomena such as wrinkles, color spots, skin relaxation and the like occur, so that the skin aging is accelerated. More seriously, if the damaged skin is not repaired in time, the skin condition may be worsened and even inflammation of various degrees may occur, resulting in serious skin problems.
At present, the method for treating inflammation caused by skin barrier damage mainly comprises the steps of regulating and recovering the skin by oral antiallergic and anti-inflammatory medicines or using light therapy or laser radio frequency, wherein the two methods have certain anti-inflammatory and repairing effects but take a long time, and when the skin is damaged and unprotected, the skin is more easily stimulated by the outside, so that the skin is subjected to secondary damage, and the physical and mental health of a patient is seriously affected.
The soluble micro-needle is a novel transdermal delivery mode, and a micron-sized needle body is utilized to pierce the skin and penetrate the epidermal layer of the skin, and then the needle body absorbs tissue fluid to be dissolved in the body to quickly release the medicine to play a role. Compared with the traditional transdermal administration route and cream smearing, the micro-needle active ingredient transfer efficiency is obviously improved, the micro-needle active ingredient can be accurately and quantitatively administered, and the micro-needle active ingredient transfer agent has wide application prospect in the fields of skin repair and treatment.
Soluble anti-inflammatory repair microneedles have been poorly studied as novel transdermal anti-inflammatory therapeutic patches. The application document CN 112370478A provides a composition with anti-inflammatory and analgesic effects, a soluble microneedle patch and a preparation method thereof, wherein the anti-inflammatory and analgesic composition comprises capsaicin, methyl salicylate, cannabis leaf extract and paeonol, but the capsaicin and methyl salicylate used have greater irritation to skin mucosa. Patent document with application number CN 211675895U discloses an antibiotic transdermal drug delivery's micropin device, antibiotic micropin has the antibacterial coating of ferrous chloride for micropin surface coating, plays antibiotic and anti-inflammatory effect through the hydroxyl free radical that Fe catalysis fenton reaction produced in local tissue, but the drug loading capacity of coating micropin is limited, and the actual reaction degree of Fe catalysis fenton reaction in skin tissue liquid is unknown, and the effect remains to be verified. Therefore, the microneedle which is mild, non-irritant and good in antibacterial and anti-inflammatory effects has important significance for repairing and protecting the skin.
Disclosure of Invention
In order to overcome the defects in the prior art, the invention provides a soluble anti-inflammatory repair microneedle and a preparation method thereof; the microneedle contains the anti-inflammatory repairing composition, and when the needle body is prepared, the anti-inflammatory repairing composition and the excipient material are integrated and gradually released in the dissolving process of the excipient material; the micro-needle has a certain penetration depth, so that the anti-inflammatory repairing composition can be better absorbed when entering a patient, and the anti-inflammatory repairing effect is improved.
The technical scheme of the invention is as follows:
a soluble anti-inflammatory repair microneedle comprising a needle body and a substrate;
the needle body comprises a shaping material and an anti-inflammatory repairing composition;
the anti-inflammatory repair composition comprises one or more of peptide repair compositions, mesenchymal stem cells and exosomes thereof, fibronectin, mussel mucin, cell growth factors, a tranquilization anti-inflammatory component and an antioxidant component.
Preferably, the anti-inflammatory repair composition comprises, in mass percent: peptide repair composition 5-30%, mesenchymal stem cell and its exosome 20-60%, fibronectin and mussel mucin 1-20%, cell growth factor 5-25%, tranquilization and anti-inflammation component 1-15%, and antioxidant component 0.5-10%.
Preferably, the peptide repair composition is one or more combination comprising oligopeptide-1, oligopeptide-3, oligopeptide-32, tripeptide-1 copper, hexapeptide-1, hexapeptide-9, hexapeptide-11, palmitoyl tripeptide-1, palmitoyl tripeptide-5, palmitoyl tetrapeptide-7, palmitoyl pentapeptide-4, decapeptide-4, collagen tripeptide; the tranquilization and anti-inflammation component comprises one or more of herba Centellae extract, folium Cannabis extract, flos Chrysanthemi extract, radix Sophorae Flavescentis extract, Perillae herba extract, cortex Betulae Pendulae or leaf extract, radix Paeoniae extract, radix Hamamelis mollis extract, bisabolol, fructus Anisi Stellati extract, and dipotassium glycyrrhizinate; the antioxidant component comprises one or more of herba Portulacae extract, Glycyrrhiza glabra extract, tetrahydro-methyl pyrimidine carboxylic acid, and allantoin; the cell growth factor comprises one or more of acidic fibroblast growth factor, epidermal cell growth factor, basic fibroblast growth factor, transforming growth factor-beta and keratinocyte growth factor.
The anti-inflammatory repairing composition comprises a repairing component, an anti-inflammatory component and an antioxidant component, and the anti-inflammatory repairing composition is matched to generate a good synergistic interaction effect, so that the anti-inflammatory repairing composition can well treat skin inflammation caused by external stimulation and the like.
Oligopeptides such as oligopeptide-1, oligopeptide-3 and oligopeptide-32, and polypeptides such as hexapeptide-9, hexapeptide-11, palmitoyl tripeptide-1 and palmitoyl tripeptide-5 have strong proliferation and mitosis effects on cells, promote collagen generation, and have important effects on cell regeneration, wound healing and damaged skin repair.
The mesenchymal stem cells and exosomes thereof can activate the immune system at the initial stage of inflammation or when chronic inflammation is weak, so that the closure of wounds with damaged skin is accelerated, tissue fibrosis is reduced, and excessive collagen deposition is inhibited. When the inflammation is serious, the mesenchymal stem cells and the exosomes thereof can also show an anti-inflammatory effect, inhibit the further generation of the inflammation and maintain the balance of the immune system of the organism.
Fibronectin regulates cell polarity, differentiation and growth, and at the early coagulation stage of the wound, fibronectin activates neutrophils, enhances their adhesion, and accelerates aggregation to the wound area. In the middle stage of wound repair, the cross-linked fibronectin helps fibroblasts to move to the wound surface, promotes the formation of granulation tissue, and accelerates wound repair.
Mussel mucin is the only known protein with high DOPA (DOPA) group content at present, and the oxidized DOPA group and the unoxidized DOPA group are mutually crosslinked to form a reticular microscopic biomembrane scaffold, so that epidermal cells, fibroblasts, vascular endothelial cells and the like of normal tissues around a wound surface are orderly promoted to creep and grow from the periphery to the middle or from the bottom to the top, and the wound surface healing is promoted.
The cell growth factor plays an important biological regulation role in various cell physiological functions and metabolic activities, can chemotaxis and induce inflammatory cells, stimulate proliferation and differentiation of target cells and promote the synthesis and secretion of extracellular matrix by the target cells, and has obvious repairing and reconstructing effects on wound surfaces.
Centella asiatica extract, cannabis sativa leaf extract, feverfew extract, sophora flavescens extract, perilla extract, birch bark or leaf extract, paeonia lactiflora extract, witch hazel extract, bisabolol, aniseed fruit extract and other various extracts are tranquilizing and anti-inflammatory components, and have synergistic effect, so that the bacteriostatic and anti-allergic effects are effectively achieved, and the microcirculation of wound surfaces is improved.
The purslane extract, the glycyrrhiza glabra extract, the tetrahydro-methyl pyrimidine carboxylic acid and the like are antioxidant components, and have the functions of effectively eliminating free radicals and resisting oxidation, so that the repair of wound skin is not influenced by ultraviolet irradiation, and the formation of scar pigment is reduced.
In the technical scheme of the invention, the mesenchymal stem cells and exosomes of the anti-inflammatory repair composition and the peptide repair composition have synergistic effect, so that the activating and immunizing effect of the stem cells and exosomes thereof is remarkably promoted, inflammation is effectively inhibited and anti-inflammatory effects are effectively realized, the wound closure is accelerated, and the cell proliferation and differentiation are promoted by matching with cytokines, fibronectin and the like, so that the repair speed of the wound skin can be effectively improved.
According to the technical scheme, the pure natural plant extract is added for anti-inflammatory and anti-oxidation, so that the anti-inflammatory effect can be further improved, and wound tissues are protected from secondary damage such as sunburn and pigmentation caused by ultraviolet radiation and the like in the repairing process.
Preferably, the needle body is a cone, and the length of the needle body is 100-2000 μm.
Preferably, the length of the needle body is 250-1000 μm.
Preferably, the excipient material comprises one or more of hyaluronic acid and sodium salt thereof, polyvinyl alcohol and polyvinylpyrrolidone.
Preferably, the molecular weight of the hyaluronic acid and the sodium salt thereof is 3kDa to 100 kDa; the alcoholysis degree of the polyvinyl alcohol is 70-95%, and the viscosity is 5-500 cps; the molecular weight of the polyvinylpyrrolidone is 30kDa-200 kDa.
Preferably, the substrate comprises one or more of hyaluronic acid and sodium salt thereof, polyvinylpyrrolidone and derivatives thereof, polyvinyl alcohol and derivatives thereof, hydroxypropyl methylcellulose, hydroxypropyl cellulose, copolymers of vinylpyrrolidone and vinyl acetate, polyethylene glycol, PVM/MA copolymer diacids and sodium/calcium salts thereof, and carboxylated chitosan.
The preparation method of the soluble anti-inflammatory repair microneedle comprises the following steps:
(1) preparing a needle fluid: dissolving the excipient in water, adding the anti-inflammatory repairing composition after uniformly stirring, and continuously stirring until uniform to obtain needle fluid;
(2) preparing a substrate:
dissolving a substrate in water, and uniformly stirring to obtain a substrate solution;
(3) preparing the microneedle:
and (2) injecting the needle body fluid obtained in the step (1) onto a microneedle mould, removing redundant needle body fluid, continuously adding a substrate fluid into the microneedle mould, standing for defoaming, heating for drying, and demoulding to obtain the microneedle.
Preferably, the material of the microneedle mould is one or a combination of polydimethylsiloxane, polymethylphenylsiloxane and polytetrafluoroethylene.
Preferably, the injection molding process for injecting the needle body fluid into the microneedle mould is one or more of vacuum injection molding, centrifugal injection molding, ultrasonic injection molding and shock injection molding.
Compared with the prior art, the invention has the beneficial effects that:
1. in the invention, the used needle body and the used substrate are both made of biocompatible materials, and the anti-inflammatory repairing effect is achieved through the combination of polypeptide, cell growth factors and natural plant extracts; in the preparation process of the needle body, the excipient and the anti-inflammatory repairing composition do not react, so that the efficacy of the anti-inflammatory repairing composition can be effectively ensured, and the microneedle has the advantages of safety and harmlessness to a human body and remarkable anti-inflammatory repairing effect.
2. According to the microneedle provided by the invention, the anti-inflammatory repairing component is wrapped inside the microneedle through the preparation of the body fluid of the microneedle and the forming process of the microneedle, so that the anti-inflammatory repairing composition participates in blood circulation after being absorbed by capillary vessels in a transdermal administration mode, and the anti-inflammatory repairing component is released and plays a corresponding role.
3. The anti-inflammatory repair microneedle provided by the invention is used for animal clinical tests and skin tissue section observation, and the results show that the microneedle can reduce inflammation and promote wound closure, and can repair skin tissue and promote tissue regeneration.
Drawings
Fig. 1 is an SEM image of anti-inflammatory repair microneedles prior to insertion;
fig. 2 is an SEM image of the substrate remaining after anti-inflammatory repair microneedle penetration;
fig. 3 is a schematic flow diagram of an anti-inflammatory repair microneedle fabrication process;
FIG. 4 is a graph of experimental microneedle repair for inflammation and hair growth in mice;
FIG. 5 is a Masson stained section of mouse epidermal tissue;
fig. 6 is a photograph of HE stained sections of epidermal tissue by microneedles.
Detailed Description
In order to make those skilled in the art better understand the technical solutions in the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
A method for preparing soluble anti-inflammatory repair microneedles comprises the following steps:
(1) preparing a needle fluid: weighing 0.1g of polyvinylpyrrolidone and 0.9g of sodium hyaluronate, dissolving in 10.0g of deionized water, and uniformly stirring to obtain a mixed solution; then 0.1g tripeptide-1 copper, 0.05g oligopeptide-1, 0.35g mesenchymal stem cell exosome, 0.03g mussel mucin, 0.15g epidermal cell growth factor, 0.01g bisabolol, 0.01g peony extract, 0.01g feverfew extract, 0.01g purslane extract and 0.01g tetrahydro methyl pyrimidine carboxylic acid are weighed and dissolved in the mixed solution to obtain a needle body fluid;
(2) preparing a substrate:
weighing 0.7g of polyvinylpyrrolidone, 0.2g of polyvinyl alcohol, 0.5g of sodium hyaluronate and 0.1g of glycerol, dissolving in 100g of deionized water, and uniformly mixing to obtain a substrate solution;
(3) preparing the microneedle:
injecting the needle body liquid obtained in the step (1) into a microneedle mould prepared from polydimethylsiloxane, carrying out microneedle injection moulding by a vacuum injection moulding process, removing redundant needle body liquid after injection moulding is finished, adding substrate liquid into the microneedle mould, standing for defoaming, heating and drying for 24 hours at the temperature of 30 ℃, and demoulding to obtain the anti-inflammatory repairing microneedle patch; SEM images of anti-inflammatory repair microneedles before puncture are shown in fig. 1, and SEM images of the remaining substrate after anti-inflammatory repair microneedles puncture are shown in fig. 2; the preparation method is shown in figure 3.
The anti-inflammatory repair microneedle obtained in this example is a 2cm by 2cm array patch with a needle body height of 600 micrometers, a needle body base of 150 micrometers, and a microneedle spacing of 200 micrometers.
Example 2
The soluble anti-inflammatory repair microneedle body fluid of the embodiment is different from that of the embodiment 1 in that 1.0g of sodium hyaluronate is weighed and dissolved in 10.0g of deionized water, and the mixture is uniformly stirred to obtain a mixed solution; then, 0.05g of oligopeptide-1, 0.05g of oligopeptide-3, 0.05g of collagen tripeptide, 0.25g of mesenchymal stem cell exosome, 0.1g of mussel mucin, 0.1g of fibronectin, 0.1g of cell growth factor, 0.01g of centella asiatica extract, 0.01g of witch hazel extract, 0.01g of feverfew extract and 0.02g of tetrahydro-methyl pyrimidine carboxylic acid were dissolved in the above mixture to obtain a needle fluid.
Example 3
The soluble anti-inflammatory repair microneedle body fluid of the embodiment is different from that of the embodiment 1 in that 1.0g of sodium hyaluronate and 0.3g of polyvinyl alcohol are weighed and dissolved in 10.0g of deionized water, and the mixture is uniformly stirred to obtain a mixed solution; then, 0.05g of oligopeptide-1, 0.05g of hexapeptide-1, 0.01g of palmitoyl tripeptide-1, 0.02g of palmitoyl tetrapeptide-7, 0.4g of mesenchymal stem cell exosome, 0.1g of fibronectin, 0.1g of cell growth factor, 0.01g of centella asiatica extract, and 0.01g of tetrahydro-methylpyrimidine carboxylic acid were weighed out and dissolved in the above-mentioned mixture to obtain a needle solution.
Comparative example 1
0.2g of polyvinylpyrrolidone and 1.0g of sodium hyaluronate are weighed and dissolved in 10.0g of deionized water to obtain the body fluid of the microneedle. 0.7g of polyvinylpyrrolidone, 0.2g of polyvinyl alcohol, 0.7g of sodium hyaluronate and 0.1g of glycerol are weighed and dissolved in 100g of deionized water to obtain the base solution of the microneedle. Injecting the body fluid of the microneedle into a microneedle mould prepared from polydimethylsiloxane, carrying out microneedle injection moulding by a vacuum injection moulding process, removing redundant needle body fluid after the injection moulding is finished, adding the microneedle substrate fluid into the microneedle mould, standing, defoaming, heating and drying at 30 ℃ for 24 hours, and then demoulding the microneedle to obtain the blank control microneedle.
Anti-inflammatory repair efficacy experiments were performed on the microneedles of example 1, the methods and results were as follows:
the first experiment method comprises the following steps:
1. 20 Balb/c mice, 10 female mice and 10 male mice were selected. Firstly, anaesthetizing a mouse, removing back hair by using an electric razor, then coating the depilatory cream on the back, scraping the depilatory cream after 10 minutes, and taking the smooth and non-traumatic back of the mouse as the clean depilatory cream, wherein the depilatory area is about 5.5 x 1.5 cm;
2. dividing the back of each mouse into four test areas, and sequentially arranging an anti-inflammatory repair microneedle test area, a comparative example microneedle test area, an inflammation blank treatment area and a blank control area (without inflammation induction) from head to tail, wherein the left image is shown in figure 5;
3. 2, 4-dinitrochlorobenzene is coated on a naked back skin test area (an anti-inflammatory repair microneedle test area, a comparative example microneedle test area and an inflammation blank treatment area) to induce the skin of the mouse to generate inflammatory lesions, and the skin has the phenomena of dryness, severe erythema, bleeding, scars, edema, scratch marks, erosion and the like;
4. experiments were performed using the microneedles of example 1 against an anti-inflammatory repair microneedle test area; the microneedle test zone of comparative example 1 was tested; the method specifically comprises the following steps: aligning the microneedle body to the dorsal epidermis of the mouse, vertically pressing the microneedle to penetrate into the skin by using the finger pad, pressing for about 5 minutes, taking off the microneedle patch twice a day, and continuously using for 21 days.
5. The mice were observed for inflammatory repair and hair growth and were visualized by Masson and HE stained sections of mouse skin tissue, and the results are shown in FIGS. 5 and 6.
Second, experimental results
1. Inflammatory repair and hair growth in the test area of the mouse back is shown in figure 4, which is shown in the right panel of figure 4.
As can be seen in fig. 4, the anti-inflammatory repair microneedle test area had no skin edema and scab after 3 weeks of microneedle treatment and the back hair had regenerated.
Compared with an anti-inflammatory repair microneedle test area, the microneedle test area still has scabbing, purulence and red swelling phenomena, but has a small amount of regenerated hair compared with an inflammation induction blank treatment area, probably because sodium hyaluronate and the like in a microneedle body shaping material can repair skin injury, promote proliferation and differentiation of epidermal cells, preserve moisture and remove oxygen radicals, but does not contain anti-inflammatory repair components, so that the regulation and control effect on inflammation is very weak.
The blank area induced by inflammation still has the phenomena of scabbing, purulence, erythema and edema.
Hair regrowth in the placebo zone.
2. Mouse skin tissue observation
The result of Masson stained section of mouse skin tissue is shown in FIG. 5, and HE stained section is shown in FIG. 6.
The results show that mild to moderate inflammatory cell infiltration continues in the epidermis and upper dermis of the test area and the inflammation blank area of the control microneedle. The anti-inflammatory repairing microneedle test area plays a beneficial role in stabilizing, repairing and regenerating body tissues due to the anti-inflammatory function of microneedle medicines, relieves and inhibits the formation of scars, and promotes the repair of inflammatory skin.
In conclusion, after the skin of the mouse with dermatitis was continuously treated for 3 weeks using the anti-inflammatory repair microneedle patch of the present invention, it was observed that inflammation phenomena of the back skin such as edema, suppuration, scab disappeared, the inflammatory repair speed was fast, and the hair regeneration was accelerated. The anti-inflammatory repair microneedle patch not only plays an obvious role in inflammation regulation, but also accelerates the repair of damaged skin.
Although the present invention has been described in detail by referring to the preferred embodiments, the present invention is not limited thereto. Various equivalent modifications or substitutions can be made on the embodiments of the present invention by those skilled in the art without departing from the spirit and scope of the present invention, and these modifications or substitutions are within the scope of the present invention/any person skilled in the art can easily conceive of the changes or substitutions within the technical scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.
Claims (10)
1. A soluble anti-inflammatory repair microneedle, comprising a needle body and a substrate;
the needle body comprises a shaping material and an anti-inflammatory repairing composition;
the anti-inflammatory repair composition comprises one or more of peptide repair compositions, mesenchymal stem cells and exosomes thereof, fibronectin, mussel mucin, cell growth factors, a tranquilization anti-inflammatory component and an antioxidant component.
2. The soluble anti-inflammatory repair microneedle of claim 1, wherein said anti-inflammatory repair composition comprises, in mass percent: peptide repair composition 5-30%, mesenchymal stem cell and its exosome 20-60%, fibronectin and mussel mucin 1-20%, cell growth factor 5-25%, tranquilization and anti-inflammation component 1-15%, and antioxidant component 0.5-10%.
3. A soluble anti-inflammatory repair microneedle according to claim 2, wherein said peptide repair composition is one or more combinations comprising oligopeptide-1, oligopeptide-3, oligopeptide-32, tripeptide-1 copper, hexapeptide-1, hexapeptide-9, hexapeptide-11, palmitoyl tripeptide-1, palmitoyl tripeptide-5, palmitoyl tetrapeptide-7, palmitoyl pentapeptide-4, decapeptide-4, collagen tripeptide; the tranquilization and anti-inflammation component comprises one or more of herba Centellae extract, folium Cannabis extract, flos Chrysanthemi extract, radix Sophorae Flavescentis extract, Perillae herba extract, cortex Betulae Pendulae or leaf extract, radix Paeoniae extract, radix Hamamelis mollis extract, bisabolol, fructus Anisi Stellati extract, and dipotassium glycyrrhizinate; the antioxidant component comprises one or more of herba Portulacae extract, Glycyrrhiza glabra extract, tetrahydro-methyl pyrimidine carboxylic acid, and allantoin; the cell growth factor comprises one or more of acidic fibroblast growth factor, epidermal cell growth factor, basic fibroblast growth factor, transforming growth factor-beta and keratinocyte growth factor.
4. The soluble anti-inflammatory repair microneedle of claim 1, wherein said excipient material comprises one or more of hyaluronic acid and its sodium salt, polyvinyl alcohol, polyvinylpyrrolidone.
5. The soluble anti-inflammatory repair microneedle according to claim 4, wherein the molecular weight of each of hyaluronic acid and its sodium salt is 3kDa-100 kDa; the alcoholysis degree of the polyvinyl alcohol is 70-95%, and the viscosity is 5-500 cps; the molecular weight of the polyvinylpyrrolidone is 30kDa-200 kDa.
6. The soluble anti-inflammatory repair microneedle of claim 1, wherein said needle body is a cone, and the length of the needle body is 100-2000 μm.
7. A soluble anti-inflammatory repair microneedle according to claim 1, wherein said substrate comprises one or more combinations of hyaluronic acid and its sodium salt, polyvinylpyrrolidone and its derivatives, polyvinyl alcohol and its derivatives, hydroxypropylmethylcellulose, hydroxypropylcellulose, copolymers of vinylpyrrolidone and vinyl acetate, polyethylene glycol, PVM/MA copolymer diacid and its sodium/calcium salt, carboxylated chitosan.
8. The method of preparing a soluble anti-inflammatory microneedle according to claim 1, wherein the process comprises:
(1) preparing a needle fluid: dissolving the excipient in water, adding the anti-inflammatory repairing composition after uniformly stirring, and continuously stirring until uniform to obtain needle fluid;
(2) preparing a substrate:
dissolving a substrate in water, and uniformly stirring to obtain a substrate solution;
(3) preparing the microneedle:
and (2) injecting the needle body fluid obtained in the step (1) onto a microneedle mould, removing redundant needle body fluid, continuously adding a substrate fluid into the microneedle mould, standing for defoaming, heating for drying, and demoulding to obtain the microneedle.
9. The method for preparing a soluble anti-inflammatory repair microneedle according to claim 8, wherein the microneedle mould is made of one or more of polydimethylsiloxane, polymethylphenylsiloxane and polytetrafluoroethylene.
10. The method for preparing soluble anti-inflammatory repair microneedles in claim 8, wherein the injection molding process for injecting the needle body fluid into the microneedle mold is one or more of vacuum injection molding, centrifugal injection molding, ultrasonic injection molding and concussion injection molding.
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