CN110755529B - Microneedle patch for improving skin acne and preparation method thereof - Google Patents

Microneedle patch for improving skin acne and preparation method thereof Download PDF

Info

Publication number
CN110755529B
CN110755529B CN201911236031.6A CN201911236031A CN110755529B CN 110755529 B CN110755529 B CN 110755529B CN 201911236031 A CN201911236031 A CN 201911236031A CN 110755529 B CN110755529 B CN 110755529B
Authority
CN
China
Prior art keywords
microneedle
substrate
acne
microneedle patch
improving skin
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN201911236031.6A
Other languages
Chinese (zh)
Other versions
CN110755529A (en
Inventor
温新国
张敏敏
萧子杰
陈航平
杨思超
任春艳
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Neworld Pharmaceutical Co ltd
Original Assignee
Guangzhou Xinji Weina Biotechnology Co ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Guangzhou Xinji Weina Biotechnology Co ltd filed Critical Guangzhou Xinji Weina Biotechnology Co ltd
Priority to CN201911236031.6A priority Critical patent/CN110755529B/en
Publication of CN110755529A publication Critical patent/CN110755529A/en
Application granted granted Critical
Publication of CN110755529B publication Critical patent/CN110755529B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/537—Salvia (sage)
    • 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
    • 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
    • A61K31/075—Ethers or acetals
    • A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/203—Retinoic acids ; Salts thereof
    • 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
    • A61K31/327—Peroxy compounds, e.g. hydroperoxides, peroxides, peroxyacids
    • 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
    • A61K31/60—Salicylic acid; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/287—Chrysanthemum, e.g. daisy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/886—Aloeaceae (Aloe family), e.g. aloe vera
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • 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
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • 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
    • 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
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/10—Anti-acne agents
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Medical Informatics (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Botany (AREA)
  • Biotechnology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Dermatology (AREA)
  • Inorganic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

The invention relates to a microneedle patch for improving skin acne and a preparation method thereof. The microneedle patch comprises a needle tip and a substrate with a hole; the raw materials of the needle tip comprise soluble materials and medicines for improving skin acne; the raw materials of the porous substrate comprise an excipient, a penetrant and a medicament for improving skin acne; the medicine for improving skin acne is at least one of vitamin A medicine, Saviae Miltiorrhizae radix extract, flos Chrysanthemi extract, benzoyl peroxide, eugenol, Aloe extract, azelaic acid and salicylic acid in needle tip and porous substrate; the soluble material comprises at least one of hyaluronic acid and a hyaluronate salt; the excipients include polyvinyl alcohol and lactic acid/glycolic acid copolymer. The microneedle patch disclosed by the invention can quickly exert a good anti-acne effect and can also effectively prevent pore blockage and secondary infection.

Description

Microneedle patch for improving skin acne and preparation method thereof
Technical Field
The invention relates to the field of medicines, in particular to a microneedle patch for improving skin acne and a preparation method thereof.
Background
Facial acne, commonly known as pox, is a common facial skin disease. The pathogenesis of acne has not yet been fully elucidated. Hormone-induced excessive secretion of lipids from sebaceous glands in genetic background, abnormal keratinization of pilosebaceous vessels, hair follicle microorganism proliferation such as Propionibacterium acnes, inflammation, immune response and the like are related to the above. Genetic factors play an important role in the development of acne, particularly severe acne; androgens are the major causative factors in sebaceous gland hyperplasia and lipid mass secretion, and other hormones such as insulin-like growth factor-1 (IGF-1), insulin, growth hormone, etc. may also be associated with acne; the massive secretion of lipid from sebaceous glands is considered as a precondition for the occurrence of acne, but the change of lipid components such as oxidized squalene, wax ester, increased content of free fatty acid, increased proportion of unsaturated fatty acid, reduced content of linoleic acid and the like are also important factors causing the occurrence of acne; the hair follicle microorganisms such as propionibacterium acnes participate in the occurrence and development of acne through natural and acquired immunity. Abnormal keratinization of pilosebaceous ducts, inflammation and immune response are the main pathological features of acne, and the inflammatory response extends through the whole process of the disease. Follicular microorganisms and/or abnormal lipids produce Interleukin (IL) -1 α and other related inflammatory mediators by activating Toll-like receptors (TLRs), IL-1 α being currently believed to be a major factor in sebaceous duct keratinization and the formation of comedones and comedones; as the disease progresses, massive accumulation of lipids leads to further proliferation of lipotrophic and anaerobic propionibacterium acnes, and adaptive immunity is activated. The ever-increasing inflammatory response induces rupture of the hair follicle wall, and lipids, microorganisms, hair, etc. enter the dermis to produce a foreign body-like response. Erythema, pigmentation and scarring often remain after the acne lesions have subsided, which is closely related to the severity of the acne, individual differences or improper treatment.
The mature external acne removing product has a certain acne removing effect, but has a slow curative effect, and is still difficult to treat the facial acne with moderate or more severe degrees.
At present, in the medical and beauty project of micro-needle acne removal, a pore channel is opened on the skin by using a metal micro-needle, and then the medicine is applied. The method increases the action efficiency of the acne removing component, activates the regeneration of skin through the micro-wound of the micro-needle, and enables excessive tissue fluid to flow out in the operation process of medical and cosmetic projects, so that the method is one of the most direct means for removing acne, and the acne removing effect is visual and obvious. However, microneedle acne removal programs are expensive and require specialized people to be found in specialized medical and aesthetic institutions. In addition, the operation process of the medical and beauty project is very painful, pain can be felt even if the anesthetic is used, and the pain and the itch are more serious after the anesthetic is used. In addition, after the operation of the medical and cosmetic project is finished, subsequent nursing products are required to be used, and the cost is high.
For the existing microneedle patch products on the market, for 'relatively mature' acne, tissue fluid exudation can occur after the products penetrate into the skin, sebum, propionibacterium acnes, staphylococcus and the like exist, the exudation is still on the surface of the skin and is wrapped by the patch to form a closed multi-bacterium environment, the uninfected skin in the patch can be infected, and more serious acne is formed. Therefore, there is a need to provide a microneedle patch having a better acne improvement effect in view of the above-mentioned problems of the existing microneedle patch.
Disclosure of Invention
Based on this, it is an object of the present invention to provide a microneedle patch for improving skin acne. The microneedle patch can rapidly exert a good anti-acne effect, and effectively prevent pore blockage and secondary infection.
The specific technical scheme is as follows:
a microneedle patch for improving skin acne comprises a needle tip and a substrate with holes; the raw materials of the needle tip comprise soluble materials and medicines for improving skin acne; the raw materials of the porous substrate comprise an excipient, a penetrant and a medicament for improving skin acne;
the medicine for improving skin acne is at least one of vitamin A medicine, Saviae Miltiorrhizae radix extract, flos Chrysanthemi extract, benzoyl peroxide, eugenol, Aloe extract, azelaic acid and salicylic acid in needle tip and porous substrate;
the excipients include polyvinyl alcohol and lactic acid/glycolic acid copolymer.
Another object of the present invention is to provide a method for preparing the microneedle patch, comprising the steps of:
(1) preparation of the perforated substrate: mixing the excipient, the penetrant and the medicine for improving skin acne with water and dichloromethane, pouring the obtained substrate solution into a microneedle substrate female die, pressing under a vacuum degree, repeating freezing and melting for 1-3 times, and dehydrating to obtain a substrate with holes;
(2) preparation of microneedle liquid: dissolving the soluble material in water, and adding the medicine for improving skin acne to obtain a microneedle solution;
(3) preparation of microneedle patch: pouring the microneedle liquid into a microneedle female die, placing the substrate with the hole on the microneedle liquid with the hole facing downwards, pressing under vacuum degree, and removing water and other solvents.
Compared with the prior art, the invention has the following beneficial effects:
according to the patch microneedle, a specific lactic acid/glycolic acid copolymer is selected to be matched with polyvinyl alcohol to serve as a substrate material, the substrate and the needle point have different solubilities, so that the substrate with the needle point dissolved still has a stable structure, a porous structure capable of containing exudates is formed in situ, a capillary-shaped microporous structure formed in the substrate by the polyvinyl alcohol in an excipient is combined, the substrate has a good rewet effect and an absorption effect on exudates, and the formed capillary-shaped microporous structure can control slow release of active ingredients of the substrate. Meanwhile, the penetrant in the substrate can also promote polyvinyl alcohol to form a capillary-shaped microporous structure, and further promote the rewet and absorption of exudates.
In the microneedle patch, the substrate has good rewet effect and absorption effect on exudates, secondary infection and pore blockage of the exudates can be effectively prevented, and the effective components of the substrate are continuously and slowly released, so that skin irritation caused by overhigh concentration of local active components due to burst release is avoided.
The invention starts from a plurality of acne pathogenesis mechanisms, and specific medicines for improving skin acne are respectively added into the needle point and the substrate with the holes, so that the acne symptom is effectively relieved from multiple angles, and the application range is wide.
Drawings
FIG. 1 is a schematic view of the structure of a negative mold 1 of example 1 and a process for preparing a substrate;
fig. 2 is a schematic view of the structure of the female mold 2 of example 1 and a process for preparing a microneedle patch;
fig. 3 is a schematic view of the action process of the microneedle patch of the present invention.
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 embodiment provides a microneedle patch for improving skin acne, which comprises a needle point and a substrate with a hole; the raw materials of the needle tip comprise soluble materials and medicines for improving skin acne; the raw materials of the porous substrate comprise an excipient, a penetrant and a medicament for improving skin acne;
the medicine for improving skin acne is at least one of vitamin A medicine, Saviae Miltiorrhizae radix extract, flos Chrysanthemi extract, benzoyl peroxide, eugenol, Aloe extract, azelaic acid and salicylic acid in needle tip and porous substrate;
the excipients include polyvinyl alcohol and lactic acid/glycolic acid copolymer.
In some embodiments, the mass ratio of the lactic acid/glycolic acid copolymer to the polyvinyl alcohol is 1-3: 1, and the preferred mass ratio is 1.5-2.5: 1.
In the research of the inventor, the polyvinyl alcohol (PVA) can be crosslinked into a net structure in the repeated freezing and thawing process, and capillary micropores can be formed after water or a solvent is volatilized, so that the absorption of exudate (capillary effect) and the control of the release speed of the drug are facilitated. However, the dissolution time of polyvinyl alcohol in the exudate is short. The inventor researches and discovers that the lactic acid/glycolic acid copolymer and polyvinyl alcohol are compounded, and the proper dosage ratio (preferably 1-3: 1, more preferably 1.5-2.5: 1) is combined, so that the dissolving time of the substrate in the exudate can be properly prolonged, after the needle tip is dissolved, the slow-soluble (long-soluble) substrate can form a stable porous shape (as shown in figure 3), further, the substrate can continuously absorb the interstitial fluid by means of back permeation, and the effective components in the substrate can be slowly and continuously released.
The microneedle tip of the invention is balanced in mechanical strength and solubility, can provide enough mechanical strength to enable the microneedle tip to enter the skin and reach a target directly, and simultaneously ensures the dissolving efficiency of the microneedle, and the dissolved components have the effects of beautifying and moisturizing the skin and can not cause allergic problems such as inflammation and the like.
After the micro-needle forms the pore channel, the medicine reaches the target, the bonding layer (the outermost layer of the micro-needle patch can be used for being fixed on the adhesive layer of the skin to play a role in fixing) temporarily protects the skin in medicine, and compared with the prior art that the skin pore channel is opened by using the metal micro-needle and then ointment is applied, the micro-needle patch is more environment-friendly and safer.
In some of these embodiments, the osmotic agent is at least one of borneol, menthol and azone, and the osmotic agent is preferably borneol.
The borneol is easy to be absorbed by the skin and easily diffused from the basal layer, not only can play a good role in calming and diminishing inflammation, but also is beneficial to forming capillary micropores in the basal layer and is beneficial to absorbing exudates through the capillary effect.
In some embodiments, the ratio of the raw material penetrant, the excipient and the drug for improving skin acne of the porous substrate is 0.3-0.7: 25-35: 0.5-7, preferably the mass ratio of 0.4-0.6: 28-32: 1 to 5. With the preferred ratio of osmotic agent to excipient, the substrate has a better absorption of the exudate.
In some of these embodiments, the soluble material comprises at least one of hyaluronic acid and a hyaluronate salt; the hyaluronate is sodium hyaluronate; the molecular weight of the sodium hyaluronate is 4000-6000, the sodium hyaluronate with the molecular weight range has good solubility, and the prepared needle point has good hardness.
In some embodiments, the mass ratio of the raw material soluble material of the needle tip to the medicine for improving skin acne is 10-14: 5 to 8.
In some of these embodiments, the soluble material further comprises glycerin; after the glycerol is added, the brittleness of the micro-needle can be improved, and the elasticity of the micro-needle can be improved.
And/or, the vitamin A medicament is selected from at least one of trans-tretinoin, isotretinoin, adapalene and tazarotene.
In some of the embodiments, the upper layer of the microneedle is in a cone shape and is exposed outside the perforated substrate, and the height of the cone is 0.1 mm-1 mm; the lower layer of the micro-needle is embedded in the hole of the substrate with the hole in a cylindrical shape, the height of the cylinder is 0.05 mm-0.5 mm, and the diameter of the bottom surface of the cone or the cylinder is 0.18 mm-0.3 mm;
and/or the hole of the substrate with the hole is a cylinder, the diameter of the bottom surface of the hole is 0.18 mm-0.3 mm, and the depth of the hole is 0.05 mm-0.5 mm.
In some of these embodiments, the microneedles are arranged on the substrate with holes at a density of 90-110/cm2。
The invention can achieve the best natural healing effect after the micro-needle is inserted into the skin by controlling the size, the shape and the array interval of the micro-needle, has low stimulation and can not cause the skin problem due to the needle hole.
In some embodiments, the medicament for improving skin acne in the needle tip comprises the following components in parts by weight: 0.4-0.6 part of vitamin A medicine, 0.2-0.4 part of benzoyl peroxide, 0.4-0.6 part of eugenol, 1-3 parts of aloe extract, 0.5-2 parts of azelaic acid and 4-6 parts of salicylic acid.
In some of these embodiments, the medicament for ameliorating skin acne in the perforated substrate comprises the following components in parts by weight: 0.2-0.4 part of salvia miltiorrhiza extract, 0.4-0.6 part of chrysanthemum extract, 0.5-2 parts of benzoyl peroxide, 0.4-0.6 part of eugenol and 1-3 parts of aloe extract.
Wherein, the vitamin A acid medicine has the functions of improving follicular sebaceous gland duct keratosis, dissolving micro acne and comedo, resisting inflammation, preventing and improving pigmentation after acne inflammation and acne scar. Benzoyl oxide, eugenol and aloe extract are used as antibacterial components, and have good effects of preventing and treating Propionibacterium acnes and inflammation. Especially, benzoyl peroxide can slowly release nascent oxygen and benzoic acid, has the effects of killing propionibacterium acnes, resisting inflammation and slightly dissolving comedo, and has no drug resistance aiming at propionibacterium acnes at present. Azelaic acid and salicylic acid have exfoliative, propionibacterium acnes-inhibiting, anti-inflammatory or mild exfoliative effects. The Saviae Miltiorrhizae radix extract and flos Chrysanthemi extract have good antiinflammatory and analgesic effects, and can be used for relieving slight wound.
The embodiment also provides a preparation method of the microneedle patch, which comprises the following steps:
(1) preparation of the perforated substrate: mixing an excipient, a penetrant and a drug for improving skin acne with water and dichloromethane, pouring the obtained substrate solution into a microneedle substrate female die, pressing under a vacuum degree, repeating freezing and melting for 1-3 times, and dehydrating to obtain a substrate with holes;
(2) preparation of microneedle liquid: dissolving the soluble material in water, and adding the medicine for improving skin acne to obtain a microneedle solution;
(3) preparation of microneedle patch: pouring the microneedle liquid into a microneedle female die, placing the substrate with the hole on the microneedle liquid with the hole facing downwards, pressing under vacuum degree, and removing the solvent and water.
The excipient and the penetrant in the substrate are helpful to be crosslinked into a reticular microporous structure after repeated freezing and thawing processes.
In some of these embodiments, the concentration of excipient in the base solution is 80-150 mg/mL;
and/or the concentration of the penetrating agent in the substrate solution is 0.5-2.5 mg/mL;
and/or the concentration of the drug for improving the skin acne in the substrate solution is 8-25 mg/mL;
and/or the concentration of the soluble material in the microneedle liquid is 10-14% mg/mL;
and/or the concentration of the drug for improving skin acne in the microneedle liquid is 1-10% mg/mL;
and/or in the step (1), the freezing process of the freeze thawing is as follows: freezing for 6 to 12 hours at the temperature of between 10 ℃ below zero and 30 ℃ below zero; the thawing process of the freezing thawing comprises the following steps: melting for 1-2 h at 20-40 ℃;
and/or the vacuum degree of the pressing under the vacuum degree in the step (1) or (3) is-0.08 to-0.05 mpa.
In some embodiments, the method for preparing the microneedle patch comprises the following steps:
(1) preparation of the perforated substrate: dissolving lactic acid/glycolic acid copolymer, eugenol, penetrating agent and benzoyl peroxide in dichloromethane, dissolving polyvinyl alcohol, radix salviae miltiorrhizae extract, chrysanthemum extract and aloe extract in water, mixing and emulsifying, pouring the obtained substrate liquid into a microneedle substrate female die, pressing under a vacuum degree, freezing and melting for 1-3 times, and dehydrating to obtain a substrate with holes;
(2) preparation of microneedle liquid: dissolving the soluble material in water, and adding the medicine for improving skin acne to obtain a microneedle solution;
(3) preparation of microneedle patch: pouring the microneedle liquid into a microneedle female die, placing the substrate with the hole on the microneedle liquid with the hole facing downwards, pressing under vacuum degree, and removing the solvent and water.
The present invention will be described in further detail with reference to specific examples.
Polyvinyl alcohol: model 1788, Shanghai Michelin Biochemical technology, Inc.;
lactic acid/glycolic acid copolymer: molecular Weight (MW): 10000, Dai handle organism;
the red sage root extract: west ampere, chun biotechnology limited;
and (3) chrysanthemum extract: west ampere, chun biotechnology limited;
aloe extract: west ampere, chun biotechnology limited;
sodium hyaluronate: molecular weight 4-6kD, SiAnmeichuan Biotech limited;
aloe extract: xian Chuang En Biotech Co., Ltd.
Example 1
The present disclosure also provides a preparation method of the microneedle patch for acne removal and beauty treatment, comprising the following steps:
(1) preparing a slow-soluble perforated substrate: weighing the following components in parts by weight and mixing: 20 parts of lactic acid/glycolic acid copolymer, 0.5 part of eugenol, 0.5 part of borneol and 1 part of benzoyl peroxide are dissolved in 80 parts of dichloromethane, and 10 parts of polyvinyl alcohol, 0.3 part of salvia miltiorrhiza extract, 0.5 part of chrysanthemum extract and 2 parts of aloe extract are dissolved in 150 parts of water. Mixing and emulsifying the components, preparing a solution, pouring the solution into a special female die 1 capable of being made into a porous shape (the shape of the female die 1 is shown in figure 1), pressing the solution under the vacuum degree of-0.07 mpa, freezing the solution at the temperature of about-20 ℃ for 6 to 12 hours, melting the solution at room temperature for 1 to 2 hours, repeatedly carrying out the freezing and melting process for 1 to 3 times, then carrying out vacuum dehydration treatment, and drying the solution to obtain the long-soluble porous substrate.
(2) Preparing soluble microneedle liquid: weighing the following components in parts by weight and mixing: 12 parts of sodium hyaluronate (5000), 75 parts of sterile water, 0.5 part of tretinoin, 0.3 part of benzoyl peroxide, 0.5 part of eugenol, 2 parts of aloe extract, 1 part of azelaic acid and 5 parts of salicylic acid. Mixing evenly and centrifuging.
(3) Preparing a microneedle patch: the prepared micro-needle liquid is added into a female die 2 (the shape of the female die 2 is shown in figure 2), and a long soluble porous substrate is placed on the micro-needle liquid, with the holes facing downwards. Pressing at room temperature and vacuum degree of-0.06 mpa, removing water and solvent in vacuum, and drying to obtain the microneedle patch.
The female mould 1 is made of Dow Corning SYLGARD184 silicone rubber. Mixing the A, B liquid of Dow Corning SYLGARD184 silicon rubber according to the weight ratio of 10: 1, pouring the mixture into a special metal male mold, and heating the mixture for 2 hours at 160 ℃. The female die made was a cuboid with a groove in the top surface, the groove being a cuboid of 110mm x 10mm (length x width x height). The top surface of the groove is provided with a raised cylindrical matrix of 100/cm2And (4) matrix arrangement. The diameter of the bottom surface of the cylinder is 0.3mm, and the height is 0.5 mm. The bottom surface of the metal plate is 110mm multiplied by 110mm, and the pressing depth is mechanically adjusted to 9mm when the long soluble perforated substrate is used, so that the thickness of the long soluble perforated substrate reaches 1 mm. The schematic diagram is shown in figure 1.
The female mould 2 is made of Dow Corning SYLGARD184 silicone rubber. Mixing the A, B liquid of Dow Corning SYLGARD184 silicon rubber according to the weight ratio of 10: 1, pouring the mixture into a special metal male mold, and heating the mixture for 2 hours at 160 ℃. The manufactured female die 2 is a cuboid, the top surface of which is provided with a groove, and the groove is a cuboid with the size of 110mm multiplied by 10 mm. The top surface of the groove is provided with a conical groove matrix of 100/cm2Arranged in a matrix and positioned to mate with the holes in the female mould 1. The diameter of the conical bottom surface is 0.3mm, and the height is 0.5 mm. When in use, the pressing depth is mechanically adjusted to 9mm, and the long soluble porous substrate and the micro-needle liquid are pressed. The schematic diagram is shown in fig. 2.
Example 2
(1) Preparing a slow-soluble perforated substrate: weighing the following components in parts by weight and mixing: 10 parts of lactic acid/glycolic acid copolymer, 0.5 part of borneol, 0.5 part of eugenol and 1 part of benzoyl peroxide are dissolved in 60 parts of dichloromethane, 20 parts of polyvinyl alcohol, 0.3 part of salvia miltiorrhiza extract, 0.5 part of chrysanthemum extract and 2 parts of aloe extract are dissolved in 180 parts of water. Mixing and emulsifying the components, preparing a solution, pouring the solution into a special female die 1 capable of being made into a porous shape, pressing the female die at a vacuum degree of-0.07 mpa, freezing the female die for 6 to 12 hours at a temperature of about-20 ℃, melting the female die for 1 to 2 hours at room temperature, repeatedly carrying out the freezing and melting process for 1 to 3 times, then carrying out vacuum dehydration and solvent drying to obtain the long-soluble porous substrate.
(2) Preparing soluble microneedle liquid: weighing the following components in parts by weight and mixing: 12 parts of sodium hyaluronate (5000), 75 parts of sterile water, 0.5 part of tretinoin, 0.3 part of benzoyl peroxide, 0.5 part of eugenol, 2 parts of aloe extract, 1 part of azelaic acid and 5 parts of salicylic acid. Mixing evenly and centrifuging.
(3) Preparing a microneedle patch: adding the prepared micro-needle liquid into the female die 2, and placing a long soluble porous substrate on the micro-needle liquid with the holes facing downwards. Pressing at room temperature under vacuum degree of-0.06 mpa. Vacuum dehydrating and solvent drying to obtain the microneedle patch.
Example 3
The present disclosure also provides a preparation method of the microneedle patch for acne removal and beauty treatment, comprising the following steps:
(1) preparing a slow-soluble perforated substrate: weighing the following components in parts by weight and mixing: 20 parts of lactic acid/glycolic acid copolymer, 0.5 part of menthol, 1 part of benzoyl peroxide and 0.5 part of eugenol are dissolved in 80 parts of dichloromethane, and 10 parts of polyvinyl alcohol, 0.3 part of salvia miltiorrhiza extract, 0.5 part of chrysanthemum extract and 2 parts of aloe extract are dissolved in 150 parts of water. Mixing and emulsifying the components, preparing a solution, pouring the solution into a special female die 1 capable of being made into a porous shape, pressing the solution under the vacuum degree of-0.07 mpa, freezing the solution at the temperature of about-20 ℃ for 6 to 12 hours, melting the solution at room temperature for 1 to 2 hours, repeatedly carrying out the freezing and melting process for 1 to 3 times, then carrying out vacuum dehydration treatment, and drying the solution to obtain the long-soluble porous substrate.
(2) Preparing soluble microneedle liquid: weighing the following components in parts by weight and mixing: 12 parts of sodium hyaluronate (5000), 75 parts of sterile water, 0.5 part of tretinoin, 0.3 part of benzoyl peroxide, 0.5 part of eugenol, 2 parts of aloe extract, 1 part of azelaic acid and 5 parts of salicylic acid. Mixing evenly and centrifuging.
(3) Preparing a microneedle patch: adding the prepared micro-needle liquid into the female die 2, and placing a long soluble porous substrate on the micro-needle liquid with the holes facing downwards. Pressing at room temperature under vacuum degree of-0.06 mpa. Vacuum dehydrating and solvent drying to obtain the microneedle patch.
Comparative example 1
(1) Preparing a perforated substrate: weighing the following components in parts by weight and mixing: 20 parts of lactic acid/glycolic acid copolymer, 1 part of benzoyl peroxide, 0.5 part of eugenol, 10 parts of polyvinyl alcohol, 0.3 part of salvia miltiorrhiza extract, 0.5 part of chrysanthemum extract and 2 parts of aloe extract are dissolved in 150 parts of water. Mixing and emulsifying the components, preparing a solution, pouring the solution into a special female die 1 capable of being made into a porous shape, pressing the female die at a vacuum degree of-0.07 mpa, freezing the female die for 6 to 12 hours at a temperature of about-20 ℃, melting the female die for 1 to 2 hours at room temperature, repeatedly carrying out the freezing and melting process for 1 to 3 times, then carrying out vacuum dehydration and solvent drying to obtain the long-soluble porous substrate.
(2) Preparing soluble microneedle liquid: weighing the following components in parts by weight and mixing: 12 parts of sodium hyaluronate (5000), 75 parts of sterile water, 0.5 part of tretinoin, 0.3 part of benzoyl peroxide, 0.5 part of eugenol, 2 parts of aloe extract, 1 part of azelaic acid and 5 parts of salicylic acid. Mixing evenly and centrifuging.
(3) Preparing a microneedle patch: adding the prepared micro-needle liquid into the female die 2, and placing a long soluble porous substrate on the micro-needle liquid with the holes facing downwards. Pressing at room temperature under vacuum degree of-0.06 mpa. Vacuum dehydrating and solvent drying to obtain the microneedle patch.
Comparative example 2
(1) Preparing a perforated substrate: weighing the following components in parts by weight and mixing: 1 part of benzoyl peroxide, 0.5 part of eugenol and 40 parts of dichloromethane are dissolved, 10 parts of polyvinyl alcohol, 0.5 part of borneol, 0.3 part of salvia miltiorrhiza extract, 0.5 part of chrysanthemum extract and 2 parts of aloe extract are dissolved in 150 parts of water. Mixing and emulsifying the components, preparing a solution, pouring the solution into a special female die 1 capable of being made into a porous shape, pressing the female die at a vacuum degree of-0.07 mpa, freezing the female die for 6 to 12 hours at a temperature of about-20 ℃, melting the female die for 1 to 2 hours at room temperature, repeatedly carrying out the freezing and melting process for 1 to 3 times, then carrying out vacuum dehydration and solvent drying to obtain the long-soluble porous substrate.
(2) Preparing soluble microneedle liquid: weighing the following components in parts by weight and mixing: 12 parts of sodium hyaluronate (5000), 75 parts of sterile water, 0.5 part of tretinoin, 0.3 part of benzoyl peroxide, 0.5 part of eugenol, 2 parts of aloe extract, 1 part of azelaic acid and 5 parts of salicylic acid. Mixing evenly and centrifuging.
(3) Preparing a microneedle patch: adding the prepared micro-needle liquid into the female die 2, and placing a long soluble porous substrate on the micro-needle liquid with the holes facing downwards. Pressing at room temperature under vacuum degree of-0.06 mpa. Vacuum dehydrating and solvent drying to obtain the microneedle patch.
Comparative example 3
The present disclosure also provides a preparation method of the microneedle patch for acne removal and beauty treatment, comprising the following steps:
(1) preparing a slow-soluble perforated substrate: weighing the following components in parts by weight and mixing: dissolving polyvinylpyrrolidone K9020 parts, benzoyl peroxide 1 part and eugenol 0.5 part in 40 parts of absolute ethyl alcohol, dissolving polyvinyl alcohol 10 parts, borneol 0.5 part, radix salviae miltiorrhizae extract 0.3 part, chrysanthemum extract 0.5 part and aloe extract 2 parts in 150 parts of water, mixing the components, preparing a solution, pouring the solution into a special female die 1 capable of being made into a porous shape, pressing the female die at a vacuum degree of-0.07 mpa, freezing the female die at a temperature of about-20 ℃ for 6-12 hours, melting the female die at room temperature for 1-2 hours, repeatedly carrying out the freezing and melting processes for 1-3 times, then carrying out vacuum dehydration and solvent drying to obtain the long-soluble porous substrate.
(2) Preparing soluble microneedle liquid: weighing the following components in parts by weight and mixing: 12 parts of sodium hyaluronate (5000), 75 parts of sterile water, 0.5 part of tretinoin, 0.3 part of benzoyl peroxide, 0.5 part of eugenol, 2 parts of aloe extract, 1 part of azelaic acid and 5 parts of salicylic acid. Mixing evenly and centrifuging.
(3) Preparing a microneedle patch: adding the prepared micro-needle liquid into the female die 2, and placing a long soluble porous substrate on the micro-needle liquid with the holes facing downwards. Pressing at room temperature under vacuum degree of-0.06 mpa. Vacuum dehydrating and solvent drying to obtain the microneedle patch.
Effect experiment 1
Formulation of pigmented microneedle patches: edible natural blue pigment is added into the base solution with the holes, and edible natural amaranth pigment is added into the microneedle solution to prepare the microneedle patch with the blue base red needle point. They were placed in an SBF-simulated body fluid and observed with a microscope. The results are shown in table 1:
TABLE 1
Figure BDA0002304897480000111
Figure BDA0002304897480000121
Effect experiment two
And (3) rewet observation: mixing SBF simulated solution with chicken blood and artificial sebum according to the ratio of 1; 1; 8 to simulate acne exudate. Wherein anticoagulant is added into the chicken blood. Wherein the artificial sebum is prepared according to the following proportion: 40% of triolein, 26% of palmitoleic acid, 20% of wax ester, 10% of squalane, 2.0% of palmitic acid and 2.0% of cholesterol. The 3 components were mixed in different proportions and 0.5g was dropped onto a glass plate. Directly after standing for 2h, weighed as a blank control. A long enough soluble perforated substrate is taken with the holes facing down on top of the liquid. After 2h the substrate was removed and weighed. The results are shown in Table 2.
TABLE 2
Figure BDA0002304897480000122
Figure BDA0002304897480000131
From the results in table 2, it can be seen that the slow dissolving apertured substrates of the present invention have good absorbency of simulated acne exudate and provide good rewet.
Effect experiment III
And (3) inspecting the antibacterial effect: dipping with sterile cotton swab to 5 × 10 concentration5～5×106CFU/mL Propionibacterium acnes was spread evenly 3 times on the surface of GIM.162 medium, the plate was rotated 60 degrees each time, and finally a cotton swab was spread around the edge of the plate for one week. The plate was covered and dried at room temperature for 5 min. 4 pieces of microneedle patches of example 1 with a diameter of 5mm, numbered 1, 2, 3 and 4, were cut and placed on the surface of the plate. Two dishes per group are labeled A, B, and after one week of incubation, the rings were observed and measured with a vernier caliperDiameter, measurements were repeated 3 times in different directions. The results are shown in Table 3.
TABLE 3
Figure BDA0002304897480000132
The results in table 3 show that the diameter of the inhibition zone of the microneedle patch of the present invention is greater than 7mm, and the microneedle patch has a good inhibition effect.
Effect experiment four
And selecting 20 volunteers with acne problems on the face of 15-30 years old, and trying 20 micro-needle patches for acne removal and beautifying for men and women. The microneedle patch of example 1 was selected for trial use, twice a week for 3 weeks, applied to the affected area for 2-3 hours, and photographed for recording. Among them, 90% of facial acnes of volunteers were reduced in redness and swelling, and sebum that had spilled significantly was reduced, and facial oil of the test subjects was reduced by using the microneedle patch of example 1. The trial feeling of the revisiting user on the microneedle patch can obviously feel the calming and anti-inflammatory effects on the acne, has slight stabbing pain feeling, but has the relieving effect of the medicine. The experimental results show that the microneedle patch disclosed by the invention has good effects of improving skin acne and removing acne and beautifying.
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 (11)

1. A microneedle patch for improving skin acne is characterized by comprising a needle point and a substrate with a hole; the raw materials of the needle tip comprise soluble materials and medicines for improving skin acne; the raw materials of the porous substrate comprise an excipient, a penetrant and a medicament for improving skin acne;
the medicine for improving skin acne is at least one of vitamin A medicine, Saviae Miltiorrhizae radix extract, flos Chrysanthemi extract, benzoyl peroxide, eugenol, Aloe extract, azelaic acid and salicylic acid in needle tip and porous substrate;
the excipient comprises polyvinyl alcohol and lactic acid/glycolic acid copolymer; the mass ratio of the lactic acid/glycolic acid copolymer to the polyvinyl alcohol is 1-3: 1;
the penetrating agent is at least one of borneol, menthol and azone.
2. The microneedle patch according to claim 1, wherein the mass ratio of the lactic acid/glycolic acid copolymer to the polyvinyl alcohol is 1.5 to 2.5: 1.
3. A microneedle patch according to claim 1, wherein the penetrating agent is borneol.
4. A microneedle patch according to claim 3, wherein the ratio by mass of the penetrating agent, the excipient and the drug for improving acne on the skin in the raw material of the substrate with holes is 0.3-0.7: 25-35: 0.5 to 7.
5. A microneedle patch according to claim 4, wherein the ratio of the raw material of the base with holes to the osmotic agent, the excipient and the drug for improving acne on skin is 0.4-0.6: 28-32: 1 to 5.
6. The microneedle patch according to claim 1, wherein the dissolvable material comprises at least one of hyaluronic acid and hyaluronate; the hyaluronate is sodium hyaluronate, and the molecular weight of the sodium hyaluronate is 4000-6000;
and/or in the raw materials of the needle tip, the mass ratio of the soluble material to the medicine for improving skin acne is 10-14: 5 to 8.
7. A microneedle patch according to claim 6, wherein the dissolvable material further comprises glycerin; and/or, the vitamin A medicament is selected from at least one of trans-tretinoin, isotretinoin, adapalene and tazarotene.
8. A microneedle patch according to any one of claims 1 to 7, wherein the upper layer of the microneedle is in the form of a cone exposed outside the base having the hole, and the height of the cone is 0.1mm to 1 mm; the lower layer of the micro-needle is embedded in the hole of the substrate with the hole in a cylindrical shape, the height of the cylinder is 0.05 mm-0.5 mm, and the diameter of the bottom surface of the cone or the cylinder is 0.18 mm-0.3 mm;
and/or the hole of the substrate with the hole is a cylinder, the diameter of the bottom surface of the hole is 0.18 mm-0.3 mm, and the depth of the hole is 0.05 mm-0.5 mm.
9. A microneedle patch according to any one of claims 1 to 7, wherein the microneedles are arranged on the base having the hole at a density of 90 to 110 pieces/cm2。
10. A method for manufacturing a microneedle patch according to any one of claims 1 to 9, comprising the steps of:
(1) preparation of the perforated substrate: mixing the excipient, the penetrant and the medicine for improving skin acne with water and dichloromethane, pouring the obtained substrate solution into a microneedle substrate female die, pressing under a vacuum degree, repeating freezing and melting for 1-3 times, and dehydrating to obtain a substrate with holes;
(2) preparation of microneedle liquid: dissolving the soluble material in water, and adding the medicine for improving skin acne to obtain a microneedle solution;
(3) preparation of microneedle patch: pouring the microneedle liquid into a microneedle female die, placing the substrate with the hole on the microneedle liquid with the hole facing downwards, pressing under vacuum degree, and removing water and other solvents.
11. The production method according to claim 10,
the concentration of the excipient in the substrate solution is 80-150 mg/mL;
and/or the concentration of the penetrating agent in the substrate solution is 0.5-2.5 mg/mL;
and/or the concentration of the drug for improving the skin acne in the substrate solution is 8-25 mg/mL;
and/or the mass concentration of the soluble material in the microneedle liquid is 10-14%;
and/or the mass concentration of the medicine for improving skin acne in the microneedle liquid is 1-10%;
and/or in the step (1), the freezing process of the freeze thawing is as follows: freezing for 6 to 12 hours at the temperature of between 10 ℃ below zero and 30 ℃ below zero; the thawing process of the freezing thawing comprises the following steps: melting for 1-2 h at 20-40 ℃; and/or the vacuum degree of the pressing under the vacuum degree in the step (1) or (3) is-0.08 to-0.05 mpa.
CN201911236031.6A 2019-12-05 2019-12-05 Microneedle patch for improving skin acne and preparation method thereof Active CN110755529B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201911236031.6A CN110755529B (en) 2019-12-05 2019-12-05 Microneedle patch for improving skin acne and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201911236031.6A CN110755529B (en) 2019-12-05 2019-12-05 Microneedle patch for improving skin acne and preparation method thereof

Publications (2)

Publication Number Publication Date
CN110755529A CN110755529A (en) 2020-02-07
CN110755529B true CN110755529B (en) 2022-02-08

Family

ID=69341094

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201911236031.6A Active CN110755529B (en) 2019-12-05 2019-12-05 Microneedle patch for improving skin acne and preparation method thereof

Country Status (1)

Country Link
CN (1) CN110755529B (en)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111450405A (en) * 2020-05-08 2020-07-28 无锡元旭生物技术有限公司 Rapid preparation method of soluble microneedle patch stock solution
CN113143844B (en) * 2021-04-30 2022-12-30 广东药科大学 Polymer microneedle patch for treating acne and preparation method thereof
CN113521279A (en) * 2021-06-11 2021-10-22 广州新济药业科技有限公司 Intelligent response type soluble microneedle and preparation method thereof
CN115737532A (en) * 2022-11-29 2023-03-07 华中科技大学 Supermolecule salicylic acid composite microneedle patch, and preparation method and application thereof
CN115944561A (en) * 2023-01-05 2023-04-11 深圳市萱嘉生物科技有限公司 Supermolecule microcrystal patch composition for reducing irritation of ionic salt and preparation method

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104755128A (en) * 2012-11-02 2015-07-01 考司美德制药株式会社 Retinoic acid microneedle
CN109528695A (en) * 2019-01-12 2019-03-29 蚌埠医学院 A kind of microneedle cutaneous patch and preparation method thereof for treating rheumatoid arthritis

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107375008B (en) * 2017-07-19 2020-07-10 广州新济药业科技有限公司 Soluble microneedle patch for whitening and preparation method thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104755128A (en) * 2012-11-02 2015-07-01 考司美德制药株式会社 Retinoic acid microneedle
CN109528695A (en) * 2019-01-12 2019-03-29 蚌埠医学院 A kind of microneedle cutaneous patch and preparation method thereof for treating rheumatoid arthritis

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
痤疮的治疗进展;张志娟;《天津药学》;20171231;第29卷(第1期);第62-66页，尤其是第62-64页外用药物治疗 *

Also Published As

Publication number Publication date
CN110755529A (en) 2020-02-07

Similar Documents

Publication Publication Date Title
CN110755529B (en) Microneedle patch for improving skin acne and preparation method thereof
CN100518794C (en) Burn cream
CN108904299B (en) Soluble microneedle with acne removing effect and preparation method thereof
KR101873827B1 (en) Micro-needle patch for pimple treatment and manufacturing method for the same
CN108186711A (en) Promote the pharmaceutical composition of wound healing
CN105250696A (en) Traditional Chinese medicine gel capable of promoting skin wound to heal and preparation method of traditional Chinese medicine gel
CN105251011B (en) A kind of spray-filming agent and preparation method thereof for superficial burns
CN112972436A (en) Application of magnolol, honokiol and derivatives thereof in preparation of scar treatment medicines and medicine composition
CN104983891A (en) Traditional Chinese medicine prescription for treating wound and preparation method of traditional Chinese medicine oil dressing based on traditional Chinese medicine prescription
WO2022022475A1 (en) Use of polypeptide in preparation of wound treatment drug
WO1995030426A1 (en) Cutaneous rejuvenating and healing product, method for its manufacture and uses thereof
CN117883370A (en) Hydrogel of traditional Chinese medicine freeze-dried powder loaded with keratin and oxidized hyaluronic acid and application thereof
CN106539804B (en) A kind of molecule traditional Chinese medicine frostlike-powder and preparation method thereof for relief from osteoarthritis pain
CN116763979A (en) Dressing capable of promoting chronic wound healing
CN109364290A (en) A kind of Lavender liposome liquid adhesive bandage and preparation method thereof
CN103007034A (en) Traditional Chinese medicine composition used for treatment of residual second-degree burn wound, and preparation method thereof
CN101837068B (en) Preparation process of zanthoxylum oil spray and application thereof
RU2329822C1 (en) Antiseptic, anti-inflammatory, analgesic
CN116747209B (en) Flexible dry patch for improving skin acne
RU2612260C1 (en) Ointment for treating superficial thermal burns
CN108310098A (en) A kind of composition of medicine and preparation method thereof for treating acne
CN219462284U (en) Pain relieving dressing for chronic wound after anorectal operation
CN115531237B (en) Acne-removing repairing composition, acne-removing repairing microneedle patch, and preparation method and application thereof
CN115569167B (en) Traditional Chinese medicine composition for treating burns and scalds as well as preparation method and application thereof
KR102194920B1 (en) Extract of mixed herbs for improving acnes, and cosmetic composition comprising the same, and mask pack containing the same

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant
TR01 Transfer of patent right
TR01 Transfer of patent right

Effective date of registration: 20231208

Address after: 510006 Room 501, floor 2, building 1, No. 1078, Xingye Avenue East, Hualong Town, Panyu District, Guangzhou, Guangdong Province

Patentee after: NEWORLD PHARMACEUTICAL Co.,Ltd.

Address before: 510663 Room 411, building G2, 31 Kefeng Road, Huangpu District, Guangzhou City, Guangdong Province

Patentee before: GUANGZHOU XINJI WEINA BIOTECHNOLOGY CO.,LTD.