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CN116808003A - Sodium aescinate gel plaster and preparation method thereof - Google Patents

Sodium aescinate gel plaster and preparation method thereof Download PDF

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Publication number
CN116808003A
CN116808003A CN202310776796.9A CN202310776796A CN116808003A CN 116808003 A CN116808003 A CN 116808003A CN 202310776796 A CN202310776796 A CN 202310776796A CN 116808003 A CN116808003 A CN 116808003A
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parts
weight
sodium
plaster
gel
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黄小龙
刘卫国
杨毅钢
黎鸠鸠
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Hunan Yige Pharmaceutical Co ltd
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Hunan Yige Pharmaceutical Co ltd
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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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • 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
    • A61K47/02—Inorganic compounds
    • 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
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • 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
    • A61K47/38—Cellulose; Derivatives thereof
    • 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
    • A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
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  • General Health & Medical Sciences (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Dermatology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Vascular Medicine (AREA)
  • Molecular Biology (AREA)
  • Pain & Pain Management (AREA)
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Abstract

The invention discloses a sodium aescinate gel plaster and a preparation method thereof, wherein the sodium aescinate gel plaster has no obvious sensitization and irritation to skin when in use, has good application comfort and is beneficial to promoting the permeation and absorption of contained medicines; specifically, the gel plaster comprises a tackifier, which can increase the tackiness of the gel plaster; the gel plaster also comprises a framework material, so that the gel plaster has better air permeability; the gel plaster also comprises a filling agent, a cross-linking agent and a cross-linking regulator, so that the physical stability of the gel plaster is improved, and the repeated uncovering property of the gel plaster is better; the gel plaster also comprises a humectant, so that the application property is improved, and meanwhile, the water can be locked for moisturizing, and the external transdermal absorption effect of the gel plaster is further improved.

Description

Sodium aescinate gel plaster and preparation method thereof
Technical Field
The invention relates to the technical field of gel preparation, in particular to sodium aescinate gel plaster and a preparation method thereof.
Background
Aescin is also called aescinic acid, and is the total name of total saponin, beta-aescin or iso-aescin extracted from seeds of Aesculus plant belonging to Aesculaceae, and belongs to triterpene saponin. The aescin has poor water solubility, and is often prepared into sodium salt to increase the solubility, and researches prove that the component with high content in the aescin sodium is aescin A, B, C, D. Sodium aescinate has effects of reducing pathological capillary permeability increase, increasing venous tension, reducing inflammatory substance exudation, relieving inflammation and swelling, relieving pain, improving blood circulation, and promoting recovery of acute closed soft tissue injury.
Research shows that the aescin sodium can promote the body to raise ACTH and cortisone plasma concentration, promote the secretion of PGF2α (prostaglandin) in blood vessel wall, eliminate free radical in body, resist inflammation, resist exudation, raise venous tension, promote venous blood flow, promote lymphatic return, improve blood circulation and microcirculation and protect blood vessel wall.
The aescin sodium has low oral bioavailability and great irritation to blood vessel. Compared with the traditional preparation, the percutaneous preparation has the advantages of avoiding the first pass effect of liver and intestine, along with no pain, no wound, convenient administration, stable blood concentration, controllable administration and the like, and has better development prospect.
Currently, the external dosage forms such as aescin sodium ointment, aerosol, liniment and the like are available on the market; however, the existing aescin external preparation has the defects of poor transdermal absorption effect, short treatment time, large skin irritation, unsatisfactory anti-swelling effect and the like. Compared with the traditional rubber plaster, the gel plaster has better affinity, permeability, perspiration resistance and repeated adhesion; therefore, a sodium aescinate gel plaster with high viscosity, good air permeability and good transdermal absorption effect is needed.
Disclosure of Invention
The invention mainly aims to provide a sodium aescinate gel plaster and a preparation method thereof, and aims to solve the problems of high viscosity, good air permeability and good transdermal absorption effect of the sodium aescinate gel plaster at present.
The technical scheme provided by the invention is as follows:
a aescin sodium gel plaster comprises a carrier layer and a plaster matrix arranged on the carrier layer; the plaster matrix comprises: 1 to 5 parts by weight of sodium aescinate, 4 to 7 parts by weight of framework material, 20 to 40 parts by weight of humectant, 5 to 20 parts by weight of tackifier, 0.5 to 10 parts by weight of microemulsion matrix, 1 to 10 parts by weight of filler, 0.1 to 0.5 part by weight of cross-linking agent, 0.1 to 3 parts by weight of cross-linking regulator, 0.5 to 5 parts by weight of pH regulator and 30 to 70 parts by weight of purified water.
Preferably, the framework material is a polyacrylic acid neutralization product; the humectant is one or more of glycerol, propylene glycol, 1, 3-butanediol and sorbitol solution; the tackifier is a plurality of polyvinyl alcohol, gelatin, sodium carboxymethylcellulose, polyacrylic acid solution and methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion; the microemulsion matrix comprises an emulsifier, a coemulsifier and an oil phase; the emulsifier is one or more of fatty acid sorbitan, polysorbate, polyoxyethylene fatty acid esters and polyoxyethylene fatty alcohol ethers; the auxiliary emulsifier is one of ethanol, propylene glycol, n-butanol, glycerol and polyethylene glycol; the oil phase is one or more of castor oil, ethyl linoleate, isopropyl myristate, caprylic acid/capric acid triglyceride; the filler is one of titanium dioxide, kaolin, talcum powder and micro silica gel; the cross-linking agent is an aluminum compound; the crosslinking regulator is edetate disodium; the pH value regulator is one of lactic acid, tartaric acid, citric acid and malic acid.
Preferably, the framework material is partially neutralized sodium polyacrylate salt; the humectant is glycerin; the tackifier is polyvinyl alcohol, gelatin, sodium carboxymethylcellulose and polyacrylic acid solution; the emulsifying agent is tween-80 and span-83; the auxiliary emulsifier is polyethylene glycol; the oil phase is isopropyl myristate; the filler is titanium dioxide; the cross-linking agent is aluminum glycinate; the pH value regulator is tartaric acid.
Preferably, the partially neutralized sodium polyacrylate salt is NP-700 (sodium polyacrylate); the plaster matrix comprises: 1 to 5 parts by weight of sodium aescinate, 4 to 7 parts by weight of NP-700, 25 to 35 parts by weight of glycerin, 1 to 2 parts by weight of polyvinyl alcohol, 1 to 2 parts by weight of gelatin, 2 to 4 parts by weight of sodium carboxymethyl cellulose, 5 to 8 parts by weight of polyacrylic acid solution, 2 to 4 parts by weight of tween-80, 2 to 4 parts by weight of span-83, 2 to 4 parts by weight of polyethylene glycol, 2 to 4 parts by weight of isopropyl myristate, 1 to 3 parts by weight of titanium dioxide, 0.1 to 0.5 part by weight of aluminum glycinate, 0.1 to 0.3 part by weight of disodium edetate, 0.5 to 1.5 parts by weight of tartaric acid, and 35 to 50 parts by weight of purified water.
Preferably, the plaster matrix comprises: 1 to 5 parts of aescin sodium, 6 parts of NP-700, 30 parts of glycerin, 2 parts of polyvinyl alcohol, 2 parts of gelatin, 2.5 parts of carboxymethylcellulose sodium, 6 parts of polyacrylic acid solution, 2 parts of tween-80, 2 parts of span-83, 2 parts of polyethylene glycol, 3 parts of isopropyl myristate, 1 part of titanium dioxide, 0.1 part of aluminum glycollate, 0.3 part of disodium edentate, 1 part of tartaric acid and 35 to 45 parts of purified water.
The invention also provides a preparation method of the aescin sodium gel plaster, which is used for preparing the aescin sodium gel plaster according to any one of the above steps, and comprises the following steps:
adding water into a prescribed amount of pH regulator, and stirring to obtain a pH regulating solution;
preparing microemulsion, wherein the microemulsion comprises sodium aescinate;
preparing water and preparing liquid;
preparing an oil phase liquid:
adding the aqueous phase preparation solution into a mixing machine for mixing, adding the microemulsion into the aqueous phase preparation solution for mixing, adding the oil phase solution for a first preset time period and continuing mixing for a second preset time period, adding the pH regulating solution for a third preset time period, adding the tackifier with a prescription amount and mixing for a fourth preset time period to obtain the plaster matrix;
coating the plaster matrix on the carrier layer to obtain the final plaster.
Preferably, the preparing micro emulsion comprises:
adding tween-80, span-83, polyethylene glycol and isopropyl myristate with the prescribed amount into the primary solvent, then carrying out water bath and stirring under the conditions of a first preset temperature and a preset stirring speed, and maintaining the fifth preset time period for 15-45 min until the components are fully and uniformly mixed to obtain an intermediate agent;
adding the prescription amount of the pharmaceutical active ingredient into the intermediate agent, then carrying out water bath and stirring under the conditions of a first preset temperature and a preset stirring speed, maintaining the sixth preset time period until the pharmaceutical active ingredient is fully and uniformly mixed to obtain the microemulsion, and storing the microemulsion at normal temperature for use.
Preferably, the preparing water is matched with the preparing liquid, and comprises the following steps:
heating purified water to a second preset temperature through a water bath, adding gelatin with a prescription amount, stirring until the gelatin is dissolved, sequentially adding disodium edentate and polyvinyl alcohol, stirring for a seventh preset time period, and then reducing the stirring rotation speed and preserving heat for later use.
Preferably, the preparing oil phase liquid comprises:
sequentially adding the prescribed amount of aluminum glycollate, NP-700, sodium carboxymethylcellulose and titanium dioxide into the prescribed amount of glycerin, stirring for an eighth preset time period, and reducing the stirring rotation speed after stirring until the mixture is uniformly dispersed for later use.
Preferably, the application of the plaster matrix to the carrier layer to obtain the finished plaster further comprises:
cutting the finished plaster, and bagging and packaging.
Through the technical scheme, the following beneficial effects can be realized:
the aescin sodium gel plaster provided by the invention has no obvious sensitization and irritation to skin when in use, has good application comfort, and is beneficial to promoting the permeation and absorption of contained medicines; specifically, the gel plaster comprises a tackifier, which can increase the tackiness of the gel plaster; the gel plaster also comprises a framework material, so that the gel plaster has better air permeability; the gel plaster also comprises a filling agent, a cross-linking agent and a cross-linking regulator, so that the physical stability of the gel plaster is improved, and the repeated uncovering property of the gel plaster is better; the gel plaster also comprises a humectant, so that the application property is improved, and meanwhile, the water can be locked for moisturizing, and the external transdermal absorption effect of the gel plaster is further improved.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are required in the embodiments or the description of the prior art will be briefly described, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and other drawings may be obtained according to the structures shown in these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a flowchart of a first embodiment of a method for preparing sodium aescinate gel patch according to the present invention;
fig. 2 is a schematic diagram showing the results of the transdermal curve of the cumulative permeation test in the first and second examples of the sodium aescinate gel patch according to the present invention.
Detailed Description
It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
The invention provides a sodium aescinate gel plaster and a preparation method thereof.
The aescin sodium gel plaster comprises a carrier layer and a plaster matrix arranged on the carrier layer; the plaster matrix comprises: 1 to 5 parts by weight of sodium aescinate, 4 to 7 parts by weight of framework material, 20 to 40 parts by weight of humectant, 5 to 20 parts by weight of tackifier, 0.5 to 10 parts by weight of microemulsion matrix, 1 to 10 parts by weight of filler, 0.1 to 0.5 part by weight of cross-linking agent, 0.1 to 3 parts by weight of cross-linking regulator, 0.5 to 5 parts by weight of pH regulator and 30 to 70 parts by weight of purified water, wherein sodium aescinate includes but is not limited to sodium aescinate A, sodium aescinate B, sodium aescinate C and sodium aescinate D.
The aescin sodium gel plaster provided by the invention has no obvious sensitization and irritation to skin when in use, has good application comfort, and is beneficial to promoting the permeation and absorption of contained medicines; specifically, the gel plaster comprises a tackifier, which can increase the tackiness of the gel plaster; the gel plaster also comprises a framework material, so that the gel plaster has better air permeability; the gel plaster also comprises a filling agent, a cross-linking agent and a cross-linking regulator, so that the physical stability of the gel plaster is improved, and the repeated uncovering property of the gel plaster is better; the gel plaster also comprises a humectant, so that the application property is improved, and meanwhile, the water can be locked for moisturizing, and the external transdermal absorption effect of the gel plaster is further improved.
Preferably, the framework material is a polyacrylic acid neutralization product; the polyacrylic acid neutralization product can be a polyacrylic acid complete neutralization product, a polyacrylic acid partial neutralization product or a mixture thereof; the humectant is one or more of glycerol, propylene glycol, 1, 3-butanediol and sorbitol solution; the tackifier is a plurality of polyvinyl alcohol, gelatin, sodium carboxymethylcellulose, polyacrylic acid solution and methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion; the microemulsion matrix comprises an emulsifier, a coemulsifier and an oil phase; the emulsifier is one or more of fatty acid sorbitan, polysorbate, polyoxyethylene fatty acid esters and polyoxyethylene fatty alcohol ethers; the auxiliary emulsifier is one of ethanol, propylene glycol, n-butanol, glycerol and polyethylene glycol; the oil phase is one or more of castor oil, ethyl linoleate, isopropyl myristate, caprylic acid/capric acid triglyceride; the filler is one of titanium dioxide, kaolin, talcum powder and micro silica gel; the cross-linking agent is an aluminum compound; the crosslinking agent is a component for adjusting the degree of progress of the crosslinking reaction between the polyacrylic acid neutralized products and the polyacrylic acid added at will, and crosslinking agents which are often used in the industry can be used; the crosslinking regulator is edetate disodium; the method has the advantages that part of free aluminum ions can be chelated, so that the crosslinking reaction rate is reduced, the crosslinking regulator is used for regulating the crosslinking speed by increasing and decreasing the dosage of the crosslinking regulator, the gel forming time is adapted to the production process, sufficient time is ensured for coating, and the gel plaster reaches proper strength in a shorter time; the pH value regulator is one of lactic acid, tartaric acid, citric acid and malic acid.
Preferably, the matrix material is a partially neutralized sodium polyacrylate salt; the humectant is glycerin; the tackifier is polyvinyl alcohol, gelatin, sodium carboxymethylcellulose and polyacrylic acid solution; the emulsifier is tween-80 (a polysorbate product) and span-83 (a fatty acid sorbitan product); the auxiliary emulsifier is polyethylene glycol; the oil phase is isopropyl myristate; the filler is titanium dioxide; the cross-linking agent is aluminum glycinate; the pH value regulator is tartaric acid.
Preferably, the partially neutralized sodium polyacrylate salt is NP-700; the plaster matrix comprises: 1 to 5 parts by weight of sodium aescinate, 4 to 7 parts by weight of NP-700, 25 to 35 parts by weight of glycerin, 1 to 2 parts by weight of polyvinyl alcohol, 1 to 2 parts by weight of gelatin, 2 to 4 parts by weight of sodium carboxymethyl cellulose, 5 to 8 parts by weight of polyacrylic acid solution, 2 to 4 parts by weight of tween-80, 2 to 4 parts by weight of span-83, 2 to 4 parts by weight of polyethylene glycol, 2 to 4 parts by weight of isopropyl myristate, 1 to 3 parts by weight of titanium dioxide, 0.1 to 0.5 part by weight of aluminum glycinate, 0.1 to 0.3 part by weight of disodium edetate, 0.5 to 1.5 parts by weight of tartaric acid, and 35 to 50 parts by weight of purified water.
Preferably, the plaster matrix comprises: 1 to 5 parts of aescin sodium, 6 parts of NP-700, 30 parts of glycerin, 2 parts of polyvinyl alcohol, 2 parts of gelatin, 2.5 parts of carboxymethylcellulose sodium, 6 parts of polyacrylic acid solution, 2 parts of tween-80, 2 parts of span-83, 2 parts of polyethylene glycol, 3 parts of isopropyl myristate, 1 part of titanium dioxide, 0.1 part of aluminum glycollate, 0.3 part of disodium edentate, 1 part of tartaric acid and 35 to 45 parts of purified water.
First embodiment:
the plaster matrix comprises: 1 part of sodium aescinate, 6 parts of NP-700, 30 parts of glycerin, 2 parts of polyvinyl alcohol, 2 parts of gelatin, 2.5 parts of sodium carboxymethylcellulose, 6 parts of polyacrylic acid solution, 2 parts of tween-80, 2 parts of span-83, 2 parts of polyethylene glycol, 3 parts of isopropyl myristate, 1 part of titanium dioxide, 0.1 part of aluminum glycinate, 0.3 part of disodium edentate, 1 part of tartaric acid and 39.1 parts of purified water.
Second embodiment:
the plaster matrix comprises: the weight portion is 5 portions of sodium aescinate, 6 portions of NP-700, 30 portions of glycerin, 2 portions of polyvinyl alcohol, 2 portions of gelatin, 2.5 portions of sodium carboxymethylcellulose, 6 portions of polyacrylic acid solution, 2 portions of tween-80, 2 portions of span-83, 2 portions of polyethylene glycol, 3 portions of isopropyl myristate, 1 portion of titanium dioxide, 0.1 portion of aluminum glycollate, 0.3 portion of disodium edentate, 1 portion of tartaric acid and 35.1 portions of purified water.
Third embodiment:
the plaster matrix comprises: 3 parts of sodium aescinate, 6 parts of NP-700, 30 parts of glycerin, 2 parts of polyvinyl alcohol, 2 parts of gelatin, 2.5 parts of sodium carboxymethylcellulose, 6 parts of polyacrylic acid solution, 2 parts of tween-80, 2 parts of span-83, 2 parts of polyethylene glycol, 3 parts of isopropyl myristate, 1 part of titanium dioxide, 0.1 part of aluminum glycinate, 0.3 part of disodium edentate, 1 part of tartaric acid and 37.1 parts of purified water.
The sodium aescinate gel plaster prepared by the method provided by the invention has good adhesiveness, specifically, the measured value of force (peeling strength) at peeling is more than 0.2N after a prescribed cylindrical probe is contacted with the adhesive surface of the plaster for a short time in a probe adhesiveness test, or the release liner is peeled by referring to the first method (initial adhesiveness measurement) of the adhesive force measuring method of the fourth part 0952 of the Chinese pharmacopoeia of 2020 edition, and when a steel ball with the diameter of 25.4 mm/weight of 57.4g is placed at the upper end horizontal line position of a test object, the steel ball stops on a plaster layer.
The aescin sodium gel plaster prepared by the microemulsion drug delivery system has good transdermal effect and long slow release time, and concretely has the specification that: the accumulation of the drug penetrating through pigskin can reach 20% after 24 hours of 700 mg/paste of aescin sodium gel plaster, and the transdermal test describes the local bioavailability and the dynamic characteristics, so that the transdermal administration of the aescin sodium gel plaster can reach the same effect as the oral administration; the transdermal administration does not need to pass through the alimentary canal, has no first pass effect, has high bioavailability, avoids the irritation and damage to gastrointestinal mucosa and liver caused by common oral administration, and greatly improves the medication safety.
The adhesion detection result of the aescin sodium gel plaster provided by the invention is as follows:
1. probe primary adhesion:
the initial tack test of the probe was performed using a texture analyzer according to ASTM D2979-01 (2009), a standard area metal probe (diameter 5 mm) was used to contact the adhesive side of the gel patch at a constant load of 100g for 1s, and the force of the probe off the adhesive side was measured (measurement results are shown in Table 1), and an average was taken 5 times, wherein the probe running speed was 0.5mm/s.
Initial adhesion (refer to the first method of adhesion assay by reference to the fourth part 0952 of the chinese pharmacopoeia, 2020 edition):
examples Peel strength (unit: N/m) Primary adhesion (Unit: N)
First embodiment 0.25 33
Second embodiment 0.23 33
TABLE 1
The initial adhesion of the probe and the initial adhesion of the rolling ball are measured, which shows that the first embodiment and the second embodiment are not different, and the effect of different amounts of the active ingredients of the medicine on the adhesive property is small.
2. Cumulative transmittance:
2.1, chromatographic conditions:
triacontyl silane bonded silica gel is used as filler (YMC Carotenode, 4.6mm×250mm,5 μm or chromatographic column with equivalent efficacy); 0.05% formic acid in water: 0.05% acetonitrile formate solution (66:34) as mobile phase, flow rate 1.0ml/min; the column temperature is 30 ℃; the detection wavelength is 220nm; the sample volume was 20. Mu.l.
2.2 transdermal test:
species of test animals: at least one of rat, mouse or pig.
Part of the test animal: abdomen or back.
The gel patch was cut into circular slices with a diameter of 1.4cm, the protective layer was peeled off, and an LOGAN automatic transdermal diffusion instrument (model: 918-12) was used for the test. Placing the treated pigskin on the back of the pig on a vertical diffusion tank, allowing the cuticle surface to face upwards and the dermis surface to face downwards, attaching the circular slice with the stripped protective layer to the central position of the cuticle of the skin, and adjusting the position of the circular slice by using a rubber ring to enable the sample to be completely exposed in the thousands of rubber rings. The device was fixed to an automated transdermal apparatus with the uppermost coverslip. The receiving chamber was filled with a degassed receiving solution (pH 7.4 phosphate buffer; weighing 6.8g of potassium dihydrogen phosphate and 1.58g of sodium hydroxide, dissolving in 1000ml of water, and suction-filtering).
Test conditions: temperature: 32 ℃ +/-0.5 ℃; rotational speed: 600rpm; receiving area: 1.54cm 2 The gas receiving chamber volume is about 12.5ml; the fluid infusion mode is as follows: goto waste; all the received solutions were taken out at 2, 4, 6, 8, 12, 14, 16, and 24 hours, respectively, and the same amount of the constant temperature received solution was replenished.
And filtering the receiving liquid at each time point in a proper amount, and taking the subsequent filtrate as a sample solution.
As shown in FIG. 2, the final transdermal curve of pig skin against pig back shows that the first embodiment has good transdermal effect and high drug permeation rate, which indicates that the cumulative drug permeation rate and permeation rate are related to the formulation specification.
As shown in fig. 1, in a first embodiment of a method for preparing a sodium aescinate gel patch according to the present invention, the method is used for preparing a sodium aescinate gel patch according to any one of the above, and the method includes the following steps:
step S110: adding water into the prescribed amount of pH regulator, and stirring to obtain pH regulating solution.
Step S120: and preparing the microemulsion, wherein the microemulsion comprises sodium aescinate.
Step S130: preparing water and preparing liquid.
Step S140: preparing oil phase liquid.
Step S150: adding the aqueous phase preparation solution into a mixing machine for mixing, slowly adding the microemulsion into the aqueous phase preparation solution for mixing, slowly adding the oil phase solution after mixing for a first preset time period (preferably 5-15 min) and continuously mixing for a second preset time period (preferably 10-30 min), slowly adding the pH regulating solution and mixing for a third preset time period (preferably 5-15 min), and then adding the tackifier (namely polyacrylic acid solution) with a prescription amount and mixing for a fourth preset time period (preferably 10-30 min) to obtain the plaster matrix.
Step S160: the plaster matrix is coated on the carrier layer by a coating machine to obtain the finished plaster.
In a second embodiment of the method for preparing sodium aescinate gel plaster provided by the invention, based on the first embodiment, step S120: the method comprises the following steps:
step S210: adding tween-80, span-83, polyethylene glycol and isopropyl myristate with the prescribed amount into the primary solvent, then carrying out water bath and stirring under the conditions of a first preset temperature (preferably 40-60 ℃) and a preset stirring speed (preferably 300 rpm) and maintaining the fifth preset time period (preferably 15-45 min) until the mixture is fully and uniformly mixed to obtain the intermediate agent.
Step S220: adding the prescribed amount of the pharmaceutically active ingredient into the intermediate agent, then carrying out water bath and stirring under the conditions of a first preset temperature (preferably 40-60 ℃) and a preset stirring speed (preferably 300 rpm) and maintaining the sixth preset time (preferably 20-60 min) until the pharmaceutically active ingredient is fully and uniformly mixed to obtain the microemulsion containing the pharmaceutically active ingredient, and storing the microemulsion at normal temperature (for example 25 ℃) for use.
In a third embodiment of the method for preparing sodium aescinate gel plaster according to the present invention, based on the first embodiment, step S130 includes the following steps:
step S310: heating purified water to a second preset temperature (preferably 30-60 ℃) through a water bath, adding the gelatin with the prescribed amount, stirring until the gelatin is dissolved, sequentially adding disodium edentate and polyvinyl alcohol, stirring for a seventh preset time (preferably 30 minutes), and then reducing the stirring rotation speed and preserving heat for later use.
In a fourth embodiment of the method for preparing sodium aescinate gel plaster according to the present invention, based on the first embodiment, step S140 includes the following steps:
step S410: sequentially adding the prescribed amount of aluminum glycinate, NP-700, sodium carboxymethylcellulose and titanium dioxide into the prescribed amount of glycerin, stirring for an eighth preset time period (preferably 30 min), and reducing the stirring rotation speed for standby after stirring until the mixture is uniformly dispersed.
In a fifth embodiment of the method for preparing sodium aescinate gel plaster according to the present invention, based on the first embodiment, step S160 further includes the following steps:
step S510: cutting the finished plaster, and bagging and packaging.
The foregoing embodiment numbers of the present invention are merely for the purpose of description, and do not represent the advantages or disadvantages of the embodiments.
The embodiments of the present invention have been described above with reference to the accompanying drawings, but the present invention is not limited to the above-described embodiments, which are merely illustrative and not restrictive, and many forms may be made by those having ordinary skill in the art without departing from the spirit of the present invention and the scope of the claims, which are to be protected by the present invention.

Claims (9)

1. The aescin sodium gel emplastrum is characterized by comprising a carrier layer and a emplastrum matrix arranged on the carrier layer; the plaster matrix comprises: 1 to 5 parts by weight of sodium aescinate, 4 to 7 parts by weight of framework material, 20 to 40 parts by weight of humectant, 5 to 20 parts by weight of tackifier, 0.5 to 10 parts by weight of microemulsion matrix, 1 to 10 parts by weight of filler, 0.1 to 0.5 part by weight of cross-linking agent, 0.1 to 3 parts by weight of cross-linking regulator, 0.5 to 5 parts by weight of pH regulator and 30 to 70 parts by weight of purified water;
the framework material is a polyacrylic acid neutralization substance; the humectant is one or more of glycerol, propylene glycol, 1, 3-butanediol and sorbitol solution; the tackifier is a plurality of polyvinyl alcohol, gelatin, sodium carboxymethylcellulose, polyacrylic acid solution and methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion; the microemulsion matrix comprises an emulsifier, a coemulsifier and an oil phase; the emulsifier is one or more of fatty acid sorbitan, polysorbate, polyoxyethylene fatty acid esters and polyoxyethylene fatty alcohol ethers; the auxiliary emulsifier is one of ethanol, propylene glycol, n-butanol, glycerol and polyethylene glycol; the oil phase is one or more of castor oil, ethyl linoleate, isopropyl myristate, caprylic acid/capric acid triglyceride; the filler is one of titanium dioxide, kaolin, talcum powder and micro silica gel; the cross-linking agent is an aluminum compound; the crosslinking regulator is edetate disodium; the pH value regulator is one of lactic acid, tartaric acid, citric acid and malic acid; the framework material is partially neutralized sodium polyacrylate.
2. The aescin sodium gel plaster according to claim 1, wherein the humectant is glycerin; the tackifier is polyvinyl alcohol, gelatin, sodium carboxymethylcellulose and polyacrylic acid solution; the emulsifying agent is tween-80 and span-83; the auxiliary emulsifier is polyethylene glycol; the oil phase is isopropyl myristate; the filler is titanium dioxide; the cross-linking agent is aluminum glycinate; the pH value regulator is tartaric acid.
3. The aescin sodium gel patch of claim 2, wherein said partially neutralized polyacrylate sodium salt is NP-700; the plaster matrix comprises: 1 to 5 parts by weight of sodium aescinate, 4 to 7 parts by weight of NP-700, 25 to 35 parts by weight of glycerin, 1 to 2 parts by weight of polyvinyl alcohol, 1 to 2 parts by weight of gelatin, 2 to 4 parts by weight of sodium carboxymethyl cellulose, 5 to 8 parts by weight of polyacrylic acid solution, 2 to 4 parts by weight of tween-80, 2 to 4 parts by weight of span-83, 2 to 4 parts by weight of polyethylene glycol, 2 to 4 parts by weight of isopropyl myristate, 1 to 3 parts by weight of titanium dioxide, 0.1 to 0.5 part by weight of aluminum glycinate, 0.1 to 0.3 part by weight of disodium edetate, 0.5 to 1.5 parts by weight of tartaric acid, and 35 to 50 parts by weight of purified water.
4. A sodium aescinate gel patch according to claim 3, wherein said patch matrix comprises: 1 to 5 parts of aescin sodium, 6 parts of NP-700, 30 parts of glycerin, 2 parts of polyvinyl alcohol, 2 parts of gelatin, 2.5 parts of carboxymethylcellulose sodium, 6 parts of polyacrylic acid solution, 2 parts of tween-80, 2 parts of span-83, 2 parts of polyethylene glycol, 3 parts of isopropyl myristate, 1 part of titanium dioxide, 0.1 part of aluminum glycollate, 0.3 part of disodium edentate, 1 part of tartaric acid and 35 to 45 parts of purified water.
5. A method for preparing a sodium aescinate gel patch according to any one of claims 1 to 4, comprising:
adding water into a prescribed amount of pH regulator, and stirring to obtain a pH regulating solution;
preparing microemulsion, wherein the microemulsion comprises sodium aescinate;
preparing water and preparing liquid;
preparing an oil phase liquid:
adding the aqueous phase preparation solution into a mixing machine for mixing, adding the microemulsion into the aqueous phase preparation solution for mixing, adding the oil phase solution for a first preset time period and continuing mixing for a second preset time period, adding the pH regulating solution for a third preset time period, adding the tackifier with a prescription amount and mixing for a fourth preset time period to obtain the plaster matrix;
coating the plaster matrix on the carrier layer to obtain the final plaster.
6. The method for preparing a sodium aescinate gel plaster according to claim 5, wherein the preparing a microemulsion comprises:
adding tween-80, span-83, polyethylene glycol and isopropyl myristate with the prescribed amount into the primary solvent, then carrying out water bath and stirring under the conditions of a first preset temperature and a preset stirring speed, and maintaining the fifth preset time period for 15-45 min until the components are fully and uniformly mixed to obtain an intermediate agent;
adding the prescription amount of the pharmaceutical active ingredient into the intermediate agent, then carrying out water bath and stirring under the conditions of a first preset temperature and a preset stirring speed, maintaining the sixth preset time period until the pharmaceutical active ingredient is fully and uniformly mixed to obtain the microemulsion, and storing the microemulsion at normal temperature for use.
7. The method for preparing the sodium aescinate gel plaster according to claim 5, wherein the preparing water phase matching preparation liquid comprises the following steps:
heating purified water to a second preset temperature through a water bath, adding gelatin with a prescription amount, stirring until the gelatin is dissolved, sequentially adding disodium edentate and polyvinyl alcohol, stirring for a seventh preset time period, and then reducing the stirring rotation speed and preserving heat for later use.
8. The method for preparing the sodium aescinate gel plaster according to claim 5, wherein the preparing the oil phase liquid comprises the following steps:
sequentially adding the prescribed amount of aluminum glycollate, NP-700, sodium carboxymethylcellulose and titanium dioxide into the prescribed amount of glycerin, stirring for an eighth preset time period, and reducing the stirring rotation speed after stirring until the mixture is uniformly dispersed for later use.
9. The method of claim 5, wherein the applying the matrix to the carrier layer to obtain the final patch further comprises:
cutting the finished plaster, and bagging and packaging.
CN202310776796.9A 2023-06-28 2023-06-28 Sodium aescinate gel plaster and preparation method thereof Pending CN116808003A (en)

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CN202310776796.9A CN116808003A (en) 2023-06-28 2023-06-28 Sodium aescinate gel plaster and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202310776796.9A CN116808003A (en) 2023-06-28 2023-06-28 Sodium aescinate gel plaster and preparation method thereof

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