CN114869861A - Compound lidocaine microneedle patch for analgesia - Google Patents

Compound lidocaine microneedle patch for analgesia Download PDF

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CN114869861A
CN114869861A CN202210298919.8A CN202210298919A CN114869861A CN 114869861 A CN114869861 A CN 114869861A CN 202210298919 A CN202210298919 A CN 202210298919A CN 114869861 A CN114869861 A CN 114869861A
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microneedle patch
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parts
lidocaine
hyaluronic acid
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李军花
吴星
马吉胜
金利泰
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Eye Hospital of Wenzhou Medical University
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Eye Hospital of Wenzhou Medical University
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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
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61P25/00—Drugs for disorders of the nervous system
    • 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
    • A61M2037/0053—Methods for producing microneedles

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
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  • Pharmacology & Pharmacy (AREA)
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  • Engineering & Computer Science (AREA)
  • Dermatology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pain & Pain Management (AREA)
  • Biomedical Technology (AREA)
  • Anesthesiology (AREA)
  • Medical Informatics (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Rheumatology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

The invention discloses a compound lidocaine microneedle patch for analgesia, which comprises a microneedle patch and a backing layer, wherein the microneedle patch is composed of a needle point layer and the backing layer, the needle point layer is made of 1-5 parts by weight of lidocaine hydrochloride, 1-5 parts by weight of prilocaine hydrochloride and 90-98 parts by weight of matrix material, the backing layer is made of 160-240 parts by weight of backing material, the matrix material is selected from one or more of hyaluronic acid, chondroitin sulfate and polyvinylpyrrolidone, and the backing material is selected from one or more of hyaluronic acid, polyvinyl alcohol and dextran.

Description

Compound lidocaine microneedle patch for analgesia
Technical Field
The invention relates to the technical field of medicines, in particular to a compound lidocaine microneedle patch for analgesia.
Background
The chemical name of lidocaine is 2- (diethylamino) -N- (2, 6-dimethylphenyl) acetamide, which has stronger anesthetic effect which is 2 times that of procaine, strong penetrating power and quick response, is considered to be an ideal local anesthetic and is used for various anesthetics and treating arrhythmia.
Prilocaine is commonly used for anesthesia in various operations such as epidural, block and infiltration. The medicine has better effect than procaine, and has similar action strength and speed as lidocaine, but has longer action time, less toxicity, fast metabolism and less accumulation.
Lidocaine and prilocaine have been used as local anesthetics for treating various pains, and most of them are injections, gels and emulsions on the market at home and abroad. However, the injection is inconvenient to administer, the compliance of patients is poor, the injection part is painful, and local tissues are easy to necrotize; the dosage of the emulsion and the gel is large, the administration frequency is frequent, the emulsion and the gel are easy to run off and pollute clothes. Therefore, the development of a compound lidocaine/prilocaine preparation which can be industrialized and has good treatment effect is urgently needed.
Transdermal drug delivery has the advantages of convenience, safety, no liver first-pass effect and the like, and has attracted much attention in recent years, but due to the barrier effect of the skin stratum corneum, the permeation rate and the permeation amount of most drugs are very low, and the treatment requirements cannot be met, so the development of a transdermal permeation promoting technology becomes the key of transdermal drug delivery, and microneedle transdermal drug delivery appearing in recent years is a novel technology for promoting the transdermal permeation of drugs. The micro needle is a needle-shaped micron-scale fine structure processed by micro-electro-mechanical technology, the length of the micro needle is generally between 25 and 1000 mu m, and most of the micro needle is made of silicon, metal, polymer and the like. The mechanism of the microneedle transdermal drug delivery system is that drugs enter the skin through tiny pores formed after microneedles penetrate the stratum corneum of the skin and enter the skin, so that the effects of promoting transdermal penetration and reaching the specific depth of the skin are achieved.
Compared with traditional oral administration and injection administration, the advantages of the microneedle are: almost has no damage and pain, and avoids the stimulation of the medicine to the intestines and stomach and the first pass effect of the liver; pore channels are formed, so that the percutaneous permeability and the bioavailability of the medicine are improved; the selectivity to the physicochemical properties and relative molecular mass of the drug is greatly reduced.
Microneedles have different classifications based on different criteria. Microneedles may be classified into solid microneedles, hollow microneedles, coated microneedles, soluble microneedles and phase-transformed microneedles, according to their mode of drug delivery. In order to effectively increase the transdermal delivery efficiency of the drug and achieve effective therapeutic concentrations of the drug, the microneedles are generally in the form of an array of multiple needles.
The soluble microneedle refers to a microneedle prepared by encapsulating a drug in a needle body using a biodegradable water-soluble polymer or polysaccharide. In use, the microneedle patch is retained in the skin for a period of time such that the needle dissolves to release the drug. Compared with solid microneedles and coated microneedles, the soluble microneedles do not generate sharp waste, increase the loading capacity, can realize controlled release of the drugs by selecting different materials and material combinations, and show significant superiority in transdermal delivery of various drugs such as polypeptides, proteins, antibodies, nucleic acids and other biomolecules.
At present, no report is found on a compound lidocaine/prilocaine microneedle patch which has stable and controllable quality and good pain relieving effect. Therefore, the compound lidocaine microneedle patch for easing pain, which has stable design quality and good treatment effect and can realize industrial production, is very necessary.
Disclosure of Invention
The invention aims to provide a compound lidocaine microneedle patch for relieving pain, which aims to solve the problems in the background technology.
In order to solve the technical problems, the invention provides the following technical scheme: the compound lidocaine microneedle patch for analgesia comprises a microneedle patch, wherein the microneedle patch consists of a needle point layer and a backing layer, the needle point layer is made of 1-5 parts by weight of lidocaine hydrochloride, 1-5 parts by weight of prilocaine hydrochloride and 90-98 parts by weight of matrix material, the backing layer is made of 160-240 parts by weight of backing material, the matrix material is selected from one or more of hyaluronic acid, chondroitin sulfate and polyvinylpyrrolidone, and the backing material is selected from one or more of hyaluronic acid, polyvinyl alcohol and dextran.
According to the technical scheme, the matrix material is a ternary composite matrix consisting of hyaluronic acid, chondroitin sulfate and polyvinylpyrrolidone.
According to the technical scheme, the backing material is polyvinyl alcohol.
According to the technical scheme, the backing material is prepared from 0.1-0.5g/mL polyvinyl alcohol aqueous solution. More preferably, the backing layer is prepared from 0.2g/mL polyvinyl alcohol in water.
According to the technical scheme, the polyvinylpyrrolidone is selected from PVP K25, PVP K30 or PVP K90.
According to the above technical scheme, the molecular weight of the hyaluronic acid is 1 × 104-1 × 105.
According to the technical scheme, the weight ratio of hyaluronic acid to chondroitin sulfate to polyvinylpyrrolidone in the matrix material is (1: 3): (1:3): (1: 3), wherein the weight ratio of the hyaluronic acid to the chondroitin sulfate to the polyvinylpyrrolidone in the matrix material is (2: 3): (2:3): (1: 2), most preferably, the weight ratio of hyaluronic acid, chondroitin sulfate and polyvinylpyrrolidone in the matrix material is 2: 2: 1.
according to the technical scheme, the needle tip layer is made of 2-4 parts by weight of lidocaine hydrochloride, 1-3 parts by weight of prilocaine hydrochloride and 93-97 parts by weight of a matrix material, and the backing layer is made of 180-220 parts by weight of a backing material.
According to the technical scheme, the needle tip layer is made of 3 parts by weight of lidocaine hydrochloride, 2 parts by weight of prilocaine hydrochloride and 95 parts by weight of matrix material, and the backing layer is made of 200 parts by weight of backing material.
Further preferably, the tip layer is made of 3 parts by weight of lidocaine hydrochloride, 2 parts by weight of prilocaine hydrochloride, 38 parts by weight of hyaluronic acid, 38 parts by weight of chondroitin sulfate, and 19 parts by weight of polyvinylpyrrolidone, and the backing layer is made of 200 parts by weight of polyvinyl alcohol.
According to the technical scheme, the pinpoint layer is made of 3 parts by weight of lidocaine hydrochloride, 2 parts by weight of prilocaine hydrochloride, 38 parts by weight of hyaluronic acid with the molecular weight of 1 x 104-1 x 105, 38 parts by weight of chondroitin sulfate and 19 parts by weight of PVP K30, and the backing layer is made of 200 parts by weight of polyvinyl alcohol.
Compared with the prior art, the invention has the following beneficial effects: the inventor of the invention unexpectedly finds out in experiments that the release and in vivo absorption of lidocaine hydrochloride and prilocaine hydrochloride in the microneedle patch are obviously improved by selecting specific matrix materials (hyaluronic acid, chondroitin sulfate and polyvinylpyrrolidone), and the clinical use curative effect of the microneedle patch is improved. In addition, by optimizing the proportion of the composite matrix material, the generation of impurities of lidocaine hydrochloride and prilocaine in the microneedle patch is effectively inhibited, and the stability of the microneedle patch in the production and storage processes is improved.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all 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.
The second aspect of the present invention provides a preparation method of the compound lidocaine/prilocaine microneedle patch, which comprises the following steps:
(1) adding a proper amount of water into lidocaine hydrochloride and prilocaine hydrochloride in a prescription amount, and fully dissolving to obtain a medicinal aqueous solution;
(2) adding a matrix material in a prescription amount into the aqueous solution of the medicine obtained in the step (1), and stirring to obtain a uniform solution;
(3) swelling the solution obtained in the step (2) for 2-6 hours, injecting the solution into a PDMS mold, centrifuging at low temperature, and drying;
(4) and (4) pouring the fully swelled backing material aqueous solution with the prescription amount into the needle point layer obtained in the step (3), centrifuging at low temperature, drying, and demolding to obtain the needle point.
Preferably, the swelling time of the solution of step (3) is 4 hours.
Preferably, the centrifugation time in the steps (3) and (4) is 10 minutes, the centrifugation speed is 4000 r/min, and the centrifugation temperature is 4 ℃.
Preferably, the drying temperature in steps (3) and (4) is 25 ℃.
Preferably, the drying time in the step (3) is 1 hour.
Preferably, the drying time in the step (4) is 12 hours.
The third aspect of the invention provides an application of the compound lidocaine/prilocaine microneedle patch in preparing a medicine for treating pain.
Preferably, the pain is neuropathic pain.
Preferably, the neuropathic pain is postherpetic neuralgia
The present invention will be further described with reference to the following examples, but the embodiments of the present invention are not limited thereto. The experimental procedures used in the following examples are all conventional procedures unless otherwise specified.
Example 1 Compound lidocaine/prilocaine microneedle patch MN1 of the invention
Weighing 0.015g of lidocaine hydrochloride and 0.01g of prilocaine hydrochloride, adding 2.5mL of purified water, and fully dissolving to obtain a medicinal water solution; adding 0.19g hyaluronic acid (relative molecular weight 1 × 104-1 × 105), 0.19g chondroitin sulfate and 0.095g PVP K30 into the above medicinal water solution sequentially, and stirring to obtain uniform solution; after the solution is swelled for 4 hours, 60 mu L of the solution is injected into a PDMS mold, and the solution is centrifuged for 10 minutes at 4 ℃ at 4000 r/min so as to fully fill the needle-shaped cavity of the mold; drying for 1 hour at 25 ℃ after centrifugation, adding 100 mu L of fully swollen 0.2g/mL polyvinyl alcohol aqueous solution backing material, centrifuging under the same condition, removing bubbles in the backing solution, drying for 12 hours at 25 ℃, and demolding to obtain the compound lidocaine/prilocaine microneedle patch MN 1.
Example 2 Compound lidocaine/prilocaine microneedle patch MN2 of the invention
And (3) adjusting the proportion of matrix materials, replacing the composition of 0.19g of hyaluronic acid, 0.19g of chondroitin sulfate and 0.095g of PVP K30 in the example 1 with the composition of 0.095g of hyaluronic acid, 0.19g of chondroitin sulfate and 0.19g of PVP K30, and obtaining the compound lidocaine/prilocaine microneedle patch MN2 by using the same formula and preparation process as the example 1.
Example 3 Compound lidocaine/prilocaine microneedle patch MN3 of the invention
And (3) adjusting the proportion of matrix materials, replacing the composition of 0.19g of hyaluronic acid, 0.19g of chondroitin sulfate and 0.095g of PVP K30 in the example 1 with the composition of 0.19g of hyaluronic acid, 0.095g of chondroitin sulfate and 0.19g of PVP K30, and obtaining the compound lidocaine/prilocaine microneedle patch MN3 by using the same formula and preparation process as the example 1.
Example 4 Compound lidocaine/prilocaine microneedle patch MN4 of the invention
Adjusting the type of the matrix material, replacing 0.095g of PVP K30 in the embodiment 1 with 0.095g of PVP K90, and obtaining the compound lidocaine/prilocaine microneedle patch MN4 by using the same formula and preparation process as the embodiment 1.
Example 5 Compound lidocaine/prilocaine microneedle patch MN5 of the invention
Adjusting the type of the matrix material, replacing 0.095g of PVP K30 in the embodiment 1 with 0.095g of PVP K25, and obtaining the compound lidocaine/prilocaine microneedle patch MN5 by using the same formula and preparation process as the embodiment 1.
Comparative example 1 Compound lidocaine/prilocaine microneedle patch C1
The kind of matrix material is adjusted, the composition of 0.19g hyaluronic acid, 0.19g chondroitin sulfate and 0.095g PVP K30 in example 1 is replaced by 0.475g hyaluronic acid, and the rest of the formula and the preparation process are the same as those in example 1, so as to obtain the compound lidocaine/prilocaine microneedle patch C1.
Comparative example 2 Compound lidocaine/prilocaine microneedle patch C2
The kind of matrix material is adjusted, the composition of 0.19g hyaluronic acid, 0.19g chondroitin sulfate and 0.095g PVP K30 in example 1 is replaced by 0.475g chondroitin sulfate, and the rest of the formula and the preparation process are the same as those in example 1, so as to obtain the compound lidocaine/prilocaine microneedle patch C2.
Comparative example 3 Compound lidocaine/prilocaine microneedle patch C3
The variety of the matrix material is adjusted, the composition of 0.19g of hyaluronic acid, 0.19g of chondroitin sulfate and 0.095g of PVP K30 in example 1 is replaced by 0.475g of PVP K30, and the rest of the formula and the preparation process are the same as those in example 1, so that the compound lidocaine/prilocaine microneedle patch C3 is obtained.
Test example 1 in vitro transdermal penetration study of Compound Lidocaine/Prainocaine microneedle Patch of the present invention
1. Test method
Taking a healthy SD rat, removing cervical vertebrae, killing, carefully cleaning abdominal hair, taking down skin, peeling adipose tissues and fascia, repeatedly cleaning with normal saline, sucking with filter paper, wrapping with tinfoil paper, and storing in a refrigerator at-80 ℃.
A saline solution containing 20% ethanol was injected into the Franz transdermal diffusion tester as a receiving solution. The test groups 1 to 8 (which correspond to the microneedle patches prepared in examples 1 to 5 of the present invention and comparative examples 1 to 3 in this order) were placed on the treated rat skin in vitro, and a force of a certain force was applied to make the microneedle patches penetrate the rat skin. Then the rat skin is placed between the supply pool and the receiving pool, the stratum corneum faces the supply pool, the skin tissue faces the receiving chamber, and the effective diffusion surface of the skin is ensured to be in contact with the liquid level of the receiving liquid. After the supply tank and the receiving chamber were fixed by clips, the diffusion tank was placed on a constant temperature magnetic stirrer, and the magnetic stirring speed was set at 300r/min and the water bath temperature in the receiving chamber was set at a constant temperature of 37 ℃. Microneedle patches were sampled 0.5mL at 0, 5, 10, 20 and 30min transdermal time, respectively, and fresh receiving solution of the same volume and temperature was immediately replenished after each sampling. The transdermal receiving sample solution was filtered through a microporous membrane (0.45 μm), and the filtrate was collected, and the content of the drug was measured by HPLC method to calculate the cumulative permeability at each time point.
2. Test results
The calculated cumulative permeability of lidocaine hydrochloride and prilocaine hydrochloride at 10min and 30min for each test group is shown in table 1 below.
TABLE 1 in vitro transdermal cumulative permeability of the Compound microneedle Patch of the present invention
Figure BDA0003564457830000081
As can be seen from the above in vitro transdermal permeability data, the cumulative permeability of the microneedle patches of examples 1 to 5 (test groups 1 to 5) of the present invention is significantly increased compared to that of comparative examples 1 to 3 (test groups 6 to 8), which confirms that the matrix material selected by the present invention has a good effect of promoting the absorption of lidocaine hydrochloride and prilocaine hydrochloride, and the microneedle patch of the present invention is expected to have a significant clinical efficacy.
Experimental example 2 stability study of Compound Lidocaine/Prainocaine microneedle Patch of the present invention
1. Test method
In this test, 6 test groups were set, and 3 samples were repeated in each test group, wherein test groups 1 to 3 used the compound lidocaine/prilocaine microneedle patch of the present invention prepared in examples 1 to 3, respectively, and test groups 4 to 6 used the compound lidocaine/prilocaine microneedle patch prepared in comparative examples 1 to 3. The 6 test groups were stored at 37 ℃ and 95% RH for 3 months, taken out and dissolved in 1mL of distilled water, and the content of remaining lidocaine hydrochloride and prilocaine hydrochloride in each test group was determined by HPLC.
2. Test results
The amounts of lidocaine hydrochloride and prilocaine hydrochloride in each test group are shown in table 2 below.
TABLE 2 content of lidocaine hydrochloride and prilocaine hydrochloride in the compound microneedle patch of the present invention
Figure BDA0003564457830000091
Figure BDA0003564457830000101
As can be seen from the stability data in the above table, compared with comparative examples 1 to 3 (test groups 4 to 6), the total impurity content of lidocaine hydrochloride and prilocaine hydrochloride after 3 months of storage of the microneedle patches of examples 1 to 3 (test groups 1 to 3) of the present invention is significantly reduced, which confirms that the selected matrix material can effectively inhibit the generation of impurities of lidocaine hydrochloride and prilocaine hydrochloride, and the microneedle patches of the present invention are expected to have good stability during production and storage
It is noted that, herein, relational terms such as first and second, and the like may be used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Also, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus.
Finally, it should be noted that: although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that changes may be made in the embodiments and/or equivalents thereof without departing from the spirit and scope of the invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims (10)

1. A compound lidocaine microneedle patch for relieving pain comprises a microneedle patch, and is characterized in that: the microneedle patch comprises a needle point layer and a backing layer, wherein the needle point layer is made of 1-5 parts by weight of lidocaine hydrochloride, 1-5 parts by weight of prilocaine hydrochloride and 90-98 parts by weight of a matrix material, the backing layer is made of 160-240 parts by weight of a backing material, the matrix material is selected from one or more of hyaluronic acid, chondroitin sulfate and polyvinylpyrrolidone, and the backing material is selected from one or more of hyaluronic acid, polyvinyl alcohol and dextran.
2. The compound lidocaine microneedle patch for analgesia according to claim 1, wherein: the matrix material is a ternary composite matrix consisting of hyaluronic acid, chondroitin sulfate and polyvinylpyrrolidone.
3. The compound lidocaine microneedle patch for analgesia according to claim 2, wherein: the backing material is polyvinyl alcohol.
4. The compound lidocaine microneedle patch for relieving pain according to claim 3, wherein: the backing material is prepared from 0.1-0.5g/mL polyvinyl alcohol aqueous solution.
5. The compound lidocaine microneedle patch for analgesia according to claim 4, wherein: the polyvinylpyrrolidone is selected from PVP K25, PVP K30 or PVP K90.
6. The compound lidocaine microneedle patch for analgesia according to claim 5, wherein: the weight ratio of hyaluronic acid, chondroitin sulfate and polyvinylpyrrolidone in the matrix material is (1: 3): (1:3): (1:3).
7. The compound lidocaine microneedle patch for relieving pain according to claim 6, wherein: the weight ratio of hyaluronic acid, chondroitin sulfate and polyvinylpyrrolidone in the matrix material is 2: 2: 1.
8. the compound lidocaine microneedle patch for analgesia according to claim 7, wherein: the needlepoint layer is made of 3 parts by weight of lidocaine hydrochloride, 2 parts by weight of prilocaine hydrochloride, 38 parts by weight of hyaluronic acid, 38 parts by weight of chondroitin sulfate, and 19 parts by weight of polyvinylpyrrolidone, and the backing layer is made of 200 parts by weight of polyvinyl alcohol.
9. The compound lidocaine microneedle patch for relieving pain according to claim 8, wherein the preparation method comprises the following steps:
(1) adding a proper amount of water into lidocaine hydrochloride and prilocaine hydrochloride in a prescription amount, and fully dissolving to obtain a medicinal aqueous solution;
(2) adding a matrix material in a prescription amount into the aqueous solution of the medicine obtained in the step (1), and stirring to obtain a uniform solution;
(3) swelling the solution obtained in the step (2) for 2-6 hours, injecting the solution into a PDMS mold, centrifuging at low temperature, and drying;
(4) and (4) pouring the fully swelled backing material aqueous solution with the prescription amount into the needle point layer obtained in the step (3), centrifuging at low temperature, drying, and demolding to obtain the needle point.
10. Use of a compound lidocaine/prilocaine microneedle patch according to any one of claims 1-8 for the preparation of a medicament for the treatment of pain.
CN202210298919.8A 2022-03-25 2022-03-25 Compound lidocaine microneedle patch for analgesia Withdrawn CN114869861A (en)

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Application publication date: 20220809