CN109124862B - Controlled-release long-acting antipyretic patch and preparation method thereof - Google Patents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F7/00—Heating or cooling appliances for medical or therapeutic treatment of the human body
- A61F7/02—Compresses or poultices for effecting heating or cooling
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F7/00—Heating or cooling appliances for medical or therapeutic treatment of the human body
- A61F2007/0059—Heating or cooling appliances for medical or therapeutic treatment of the human body with an open fluid circuit
- A61F2007/0063—Heating or cooling appliances for medical or therapeutic treatment of the human body with an open fluid circuit for cooling
- A61F2007/0068—Heating or cooling appliances for medical or therapeutic treatment of the human body with an open fluid circuit for cooling evaporating on the spot to be cooled
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- A61F7/00—Heating or cooling appliances for medical or therapeutic treatment of the human body
- A61F7/02—Compresses or poultices for effecting heating or cooling
- A61F2007/0203—Cataplasms, poultices or compresses, characterised by their contents; Bags therefor
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- A61F7/00—Heating or cooling appliances for medical or therapeutic treatment of the human body
- A61F7/02—Compresses or poultices for effecting heating or cooling
- A61F2007/0244—Compresses or poultices for effecting heating or cooling with layers
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F7/00—Heating or cooling appliances for medical or therapeutic treatment of the human body
- A61F7/02—Compresses or poultices for effecting heating or cooling
- A61F2007/0261—Compresses or poultices for effecting heating or cooling medicated
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Abstract
The invention belongs to the technical field of antipyretic patches, and particularly relates to a controlled-release long-acting antipyretic patch and a preparation method thereof. The invention provides a controlled-release long-acting antipyretic patch, which comprises: the back lining layer, the hydrogel layer and the protective film layer are arranged in sequence; microcapsules are dispersed in the hydrogel layer, and the microcapsules are wrapped with volatile essential oil; the microcapsule is a hydrophilic chitosan nano microcapsule. In the invention, the microcapsule is dispersed in the hydrogel layer of the cooling patch, the volatile essential oil is wrapped by the microcapsule, so that the volatile essential oil can be slowly volatilized, and the duration time of the cooling effect of the cooling patch is prolonged.
Description
Technical Field
The invention belongs to the technical field of antipyretic patches, and particularly relates to a controlled-release long-acting antipyretic patch and a preparation method thereof.
Background
The heat production and heat dissipation of normal human body keep dynamic balance, but under many diseases, the heat production of the body is increased and the heat dissipation is reduced due to pyrogen and pyrogen factors, so that the body temperature is raised or fever is caused. Fever and fever are common physiological and pathological reactions of people. When the body is heated, the heat in the body is mainly dissipated in the modes of convection, radiation, evaporation and the like, and meanwhile, the hypothalamic thermoregulation center enhances the heat dissipation of the body by expanding blood vessels, accelerating circulation, sweating and the like. It is worth noting that the rapid dissipation of body heat often causes secondary cold and muscle trembling, and induces rapid increase of heat generation in the body, which leads to vicious circle. Continuous high fever easily causes convulsion and coma, and particularly has more serious influence on immature infants such as immune systems, so that measures are needed to be taken in time to reduce fever and temperature.
Clinically, the treatment for fever mainly comprises drug cooling and physical cooling, and the specific treatment is determined according to etiology, physique and fever degree of patients. Wherein, the medicine cooling has the advantages of obvious effect, simple use method and the like. The medicine cooling comprises oral taking, intramuscular injection, transfusion and the like of antipyretic medicines, and the antipyretic medicines commonly used at present comprise aspirin, paracetamol, indomethacin, ibuprofen and the like. In recent years, people pay attention to adverse reactions of drug therapy, and the side effects of drug cooling are large, so that the traditional Chinese medicine is particularly not suitable for infant fever reduction. Moreover, some antipyretic drugs seriously damage liver, kidney and digestive tract of patients and have a lot of contraindications, patients with an antipyretic drug allergy history should not use the drugs, patients with allergic constitution and patients with low liver function should be cautious or stop taking the antipyretic drugs, and in addition, some antipyretic drugs are not suitable for long-term taking due to side effects. According to the safe, effective and non-toxic clinical medication concept advocated by the world health organization, the physical method is applied to reduce the temperature and is greatly concerned by people. Traditional physical cooling methods including room temperature control, ice compress and alcohol bath have been widely used in clinical practice. At present, products for cooling by a physical method comprise an ice bag, a liquid cooling bag and the like, the traditional ice bag is usually a plastic film or a waterproof cloth bag, and when the ice bag is used, a frozen ice block is placed in the bag and is applied to the forehead or other parts. The liquid cooling bag is usually made of plastic material and is sealed with liquid with large specific heat capacity, such as ethanol, propylene glycol and the like, and the liquid is placed in a refrigerator for freezing before use, and the use of the liquid cooling bag is limited because the liquid cooling bag needs pre-freezing treatment and other processes before use.
The product cooled by a physical method is also provided with an antipyretic patch, and the antipyretic patch achieves the effect of reducing body temperature through the physical process of water vaporization and heat absorption after moisture permeates skin according to the transdermal absorption principle. At present, most of the antipyretic patches mainly composed of hydrogel are prepared by adding water, a natural cooling agent and an active substance to hydrogel based on polymer hydrogel. When in use, the hydrogel takes away heat through water evaporation, thereby achieving the purposes of cooling and defervescing, and meanwhile, the freshener and the active substance added in the hydrogel locally play the roles of cooling and easing pain. The antipyretic patch is simple and convenient to use, and is suitable for clinical symptoms of acute fever, headache, sprain and the like of children. However, the existing cooling patch has short duration of cooling effect and no fast-response temperature sensitivity.
Disclosure of Invention
In view of the above, the invention provides a controlled-release long-acting antipyretic patch and a preparation method thereof, which are used for solving the problems that the existing antipyretic patch has short duration of antipyretic effect and does not have quick-response temperature sensitivity.
The specific technical scheme of the invention is as follows:
a controlled release, long-acting antipyretic patch comprising: the back lining layer, the hydrogel layer and the protective film layer are arranged in sequence;
microcapsules are dispersed in the hydrogel layer, and the microcapsules are wrapped with volatile essential oil;
the microcapsule is a hydrophilic chitosan nano microcapsule.
Preferably, the particle size of the hydrophilic chitosan nano-microcapsule is 50 nm-1000 nm.
Preferably, the mass ratio of the hydrophilic chitosan nano microcapsule to the hydrogel layer is 0-30: 60 to 100.
Preferably, the volatile essential oil comprises one or more of peppermint oil, borneol, pine root oil, lemon essential oil and eucalyptus essential oil.
Preferably, the hydrogel layer is prepared from a polymer gel;
the high-molecular gel comprises a high-molecular polymer, a humectant, a cross-linking agent and a cross-linking regulator.
Preferably, the mass ratio of the high molecular polymer, the humectant, the crosslinking agent and the crosslinking regulator is 15-30: 10-30: 0.01-2: 0.05 to 0.5.
The invention also provides a preparation method of the controlled-release long-acting antipyretic patch, which comprises the following steps:
dispersing the hydrophilic chitosan nano microcapsule wrapped with volatile essential oil in a hydrogel layer, and respectively adhering a back lining layer and a protective film layer on two sides of the hydrogel layer to obtain the controlled-release long-acting antipyretic patch.
Preferably, the hydrophilic chitosan nano-microcapsule coated with volatile essential oil is prepared by the following method:
dissolving hydrophilic chitosan in deionized water to prepare a chitosan aqueous solution;
dissolving volatile essential oil in an organic solvent to obtain an essential oil solution, dispersing the essential oil solution in an emulsifier aqueous solution, then uniformly mixing the essential oil solution with the chitosan aqueous solution, adjusting the pH value of the mixture to carry out a re-coagulation reaction, and then spraying by adopting a coaxial nozzle to obtain the hydrophilic chitosan nano microcapsule coated with the volatile essential oil.
Preferably, the nozzle velocity of the spray is 1ml/min to 15 ml/min.
Preferably, the air pressure of the spraying is 0.3 bar-0.5 bar;
the frequency of the spraying is 40 Hz-200 Hz.
In summary, the present invention provides a controlled release long-acting antipyretic patch, comprising: the back lining layer, the hydrogel layer and the protective film layer are arranged in sequence; microcapsules are dispersed in the hydrogel layer, and the microcapsules are wrapped with volatile essential oil; the microcapsule is a hydrophilic chitosan nano microcapsule. In the invention, the microcapsule is dispersed in the hydrogel layer of the antipyretic patch, and the volatile essential oil is wrapped by the microcapsule, so that the volatile essential oil can be slowly volatilized, the defects that the volatile essential oil is strong in volatility and easy to oxidize, the effective components are easy to lose, the color and the texture of the volatile essential oil are easy to change along with the prolonging of the storage time and the like are overcome, and the duration time of the antipyretic effect of the antipyretic patch is prolonged; the cooling patch has double cooling functions, on one hand, the cooling effect is achieved through the energy conversion effect of the hydrogel layer and the heat absorption through vaporization, and on the other hand, the volatile essential oil wrapped by the micro-capsules arranged on the hydrogel layer can play a cooling effect through the skin; when the antipyretic patch is used, the higher the body temperature of a patient is, the higher the speed of converting the bound water in the hydrogel layer into free water is, so that the volatile essential oil in the hydrophilic chitosan nano microcapsule is released more quickly, and the antipyretic patch has quick-response temperature sensitivity.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below.
Fig. 1 is a peppermint oil release profile of hydrophilic chitosan nano-microcapsules in an example of the present invention.
Detailed Description
The invention provides a controlled-release long-acting antipyretic patch and a preparation method thereof, which are used for solving the problems that the existing antipyretic patch is short in duration of antipyretic effect and free of quick-response temperature sensitivity.
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.
A controlled release, long-acting antipyretic patch comprising: the back lining layer, the hydrogel layer and the protective film layer are arranged in sequence;
the hydrogel layer is dispersed with microcapsules, and the microcapsules are wrapped with volatile essential oil;
the microcapsule is hydrophilic chitosan nanometer microcapsule.
In the invention, the microcapsule is dispersed in the hydrogel layer of the antipyretic patch, and the volatile essential oil is wrapped by the microcapsule, so that the volatile essential oil can be slowly volatilized, the defects that the volatile essential oil is strong in volatility and easy to oxidize, the effective components are easy to lose, the color and the texture of the volatile essential oil are easy to change along with the prolonging of the storage time and the like are overcome, and the duration time of the antipyretic effect of the antipyretic patch is prolonged; the cooling patch has double cooling functions, on one hand, the cooling effect is achieved through the energy conversion effect of the hydrogel layer and the heat absorption through vaporization, and on the other hand, the volatile essential oil wrapped by the micro-capsules arranged on the hydrogel layer can play a cooling effect through the skin; when the antipyretic patch is used, the higher the body temperature of a patient is, the higher the speed of converting the bound water in the hydrogel layer into free water is, so that the volatile essential oil in the hydrophilic chitosan nano microcapsule is released more quickly, and the antipyretic patch has quick-response temperature sensitivity.
In the invention, the particle size of the hydrophilic chitosan nano microcapsule is 50 nm-1000 nm.
The particle size of the hydrophilic chitosan nano microcapsule is preferably 200nm to 1000 nm.
In the invention, the mass ratio of the hydrophilic chitosan nano microcapsule to the hydrogel layer is 0-30: 60 to 100.
The mass ratio of the hydrophilic chitosan nano microcapsule to the hydrogel layer is preferably 10-20: 70-80.
In the invention, the volatile essential oil comprises one or more of peppermint oil, borneol, pine root oil, lemon essential oil and eucalyptus essential oil.
Peppermint oil is an active ingredient extracted from stems and leaves of peppermint, has the effects of clearing away summer heat and is widely applied to products such as cooling oil, analgesics, toothpaste, candies and the like. The oleum Pini is active ingredient with tranquilizing effect obtained from temple of Pinus massoniana Linne. The peppermint oil, the borneol, the pine root oil, the lemon essential oil and the eucalyptus essential oil are extracts from natural plants, are safe and have lasting fragrance, can soothe nerves and help sleep, and are beneficial to playing a role of cooling.
The oleum Menthae Dementholatum is prepared from stem and leaf of fresh herba Menthae by distilling, and has special refreshing fragrance. The peppermint oil has strong volatility, is easy to oxidize and lose, and the color and the texture of the peppermint oil can also change along with the prolonging of the storage time.
The volatile essential oil can also comprise edible aromatic components, so that the cooling paste has flower fragrance or fruit temperature, and the cooling paste is easier to use by patients.
The back lining layer, the hydrogel layer and the protective film layer of the cooling paste are sequentially pasted, the protective film layer protects the hydrogel layer from the environment, the hydrogel layer is a removable adhesive film, the adhesive film can be selected from transparent or opaque cellophane or plastic film and the like, and can be a polyethylene film for compounding or a high-temperature resistant polyester film and the like. The hydrogel layer is the main body of the antipyretic patch, adopts water-soluble polymer gel with good energy conversion function as a carrier, and is added with one or more natural plant extract components or other active components, so that the water retention property is good.
The invention relates to a cooling patch, in particular to a local patch, which is applied on the skin surface of a user when being locally used and is kept on the application part for a certain time so as to achieve the cooling effect. The antipyretic patch has the characteristics of strong hydrophilicity, good air permeability, good water permeability, strong water absorption, good water retention, strong tensile strength, strong elasticity and the like. The hydrogel layer of the cooling patch has good biocompatibility, is clean and safe, and does not stimulate the skin. The cooling patch can be applied to any suitable local parts of arms, legs, trunk, head and the like, and the added natural active ingredients such as volatile essential oil and the like have cooling and pain relieving effects, so that the functions of the cooling patch, such as pain relieving, swelling reducing, cooling, refreshing, muscle relaxing, sleep improving and the like, are expanded, and the cooling patch is suitable for multiple fields of medicines, sports goods, daily necessities and the like.
In the invention, the hydrogel layer is prepared from a high-molecular gel;
the high molecular gel comprises high molecular polymer, humectant, cross-linking agent and cross-linking regulator.
The mass ratio of the high molecular polymer to the humectant to the crosslinking agent to the crosslinking regulator is 15-30: 10-30: 0.01-2: 0.05 to 0.5.
The mass ratio of the high molecular polymer to the humectant to the crosslinking agent to the crosslinking regulator is preferably 20-25: 15-20: 0.1-0.2: 0.1 to 0.2.
In the present invention, the high molecular polymer is selected from gelatin, starch, agar, mannan, carbomer, alginic acid, polyacrylic acid, sodium polyacrylate, dextrin, methyl cellulose, sodium methyl cellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, carboxyvinyl polymer, polyvinyl alcohol, polyethylene special bags of willow branches, framed by bamboo, for building dykes pyrrolidone, gum arabic, tragacanth gum, karaya gum, starch acrylate copolymer or sodium starch acrylate; the high molecular weight polymer may also be selected from gelatin, starch, agar, mannan, carbomer, alginic acid, polyacrylic acid, sodium polyacrylate, dextrin, methyl cellulose, sodium methyl cellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, carboxyvinyl polymer, polyvinyl alcohol, polyethylene special bags of willow branches, framed by bamboo, for building dykes pyrrolidone, gum arabic, tragacanth gum, karaya gum, starch acrylate copolymer, or a metal salt of sodium starch acrylate; the high molecular weight polymer may also be selected from gelatin, starch, agar, mannan, carbomer, alginic acid, polyacrylic acid, sodium polyacrylate, dextrin, methyl cellulose, sodium methyl cellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, carboxyvinyl polymer, polyvinyl alcohol, polyvinyl pyrrolidone, gum arabic, tragacanth gum, karaya gum, starch acrylate copolymer or a product of sodium starch acrylate by organic or inorganic crosslinking.
The macromolecular gel prepared from the polyvinyl alcohol and the polyacrylic acid has good biocompatibility and can not cause irritation or discomfort to human skin. It is noted that polyvinyl alcohol can be replaced by dextran, and the macromolecular gel prepared from dextran and polyacrylic acid has good swelling property and water retention property.
In the present invention, the humectant is selected from glycerin, sorbitol, diethylene glycol, 1, 3-butylene glycol, glycerin, propylene glycol, or polyethylene glycol. The cross-linking agent is selected from aluminum trichloride, aluminum oxide or aluminum glycollate. The crosslinking regulator is selected from citric acid, tartaric acid, glacial acetic acid, citric acid or formic acid.
In the invention, the polymer gel also comprises a cosolvent, wherein the cosolvent is an organic cosolvent and is used for dissolving active ingredients. The organic cosolvent is selected from N-methyl-2-pyrrolidone, diethyl toluamide, ethanol, methanol, polyethylene glycol or isopropyl myristate. The mass percentage of the cosolvent in the polymer gel is 0.1-5%.
The polymer gel also comprises p-hydroxybenzoate ester, anionic, cationic and nonionic surfactants, etc. The hydrogel layer further comprises oils selected from Simmondsia chinensis oil or steamed sesame oil; the hydrogel layer further comprises a pH regulator to regulate the pH value of the hydrogel layer to 4.0-7.0, wherein the pH regulator is selected from malic acid, tartaric acid or diisopropanolamine; the hydrogel layer further comprises an alcohol selected from ethanol.
In the invention, the backing layer is made of flexible material, so that the shoe pad is convenient to adapt to human body movement. And the flexible material is a breathable material. The air-permeable material is selected from non-woven fabric, spandex or flannel; the breathable material may also be selected from the group consisting of nonwoven fabrics, woven fabrics, laminates of spandex or flannel with polyethylene films, ethylene terephthalate films, polyvinyl chloride films, ethylene -acetic acid, vinyl ester copolymer films, or polyurethane films.
The cooling paste has double cooling functions, and on one hand, the cooling paste achieves rapid physical cooling by utilizing the energy conversion function of the hydrogel layer and absorbing heat through vaporization; on the other hand, volatile essential oil wrapped by the microcapsule arranged on the hydrogel layer can play a role in defervescence through the skin. The microcapsule in the antipyretic patch disclosed by the invention wraps the volatile essential oil, so that the defects that the volatile essential oil is strong in volatility and easy to oxidize, the effective components are easy to lose, the color and the texture of the volatile essential oil are easy to change along with the prolonging of the storage time and the like are overcome, and the duration time of the antipyretic effect of the antipyretic patch is ensured and prolonged. And the microcapsules are hydrophilic chitosan nano microcapsules, when the cooling patch is used, the higher the body temperature of a patient is, the higher the speed of converting the bound water in the hydrogel layer into free water is, so that the volatile essential oil in the hydrophilic chitosan nano microcapsules is released more quickly, and the cooling patch has quick-response temperature sensitivity. The antipyretic patch has the advantages of good skin permeation effect of volatile essential oil, no toxic or side effect of raw materials contained in the antipyretic patch, good skin compatibility, no skin irritation, no residue, high water content, good water retention property, strong toughness, good air permeability and no discomfort to skin. The cooling paste disclosed by the invention does not need refrigeration equipment when in use, does not need precooling time, is opened when in use, is pasted on the forehead or other parts, does not need preparation time, can be used at any time, is convenient to use, has the effects of cooling, easing pain, cooling and refreshing, is clean and safe and nontoxic, is particularly suitable for children, can be used for cold compress physiotherapy, pain relief, summer heat relieving, cooling and the like, can also be used for refreshing, relaxing muscles, improving sleep, moisturizing skin, beautifying and the like, and can be applied to the fields of medicines, sports goods, beautifying, daily necessities and the like.
The invention also provides a preparation method of the controlled-release long-acting antipyretic patch, which comprises the following steps:
dispersing hydrophilic chitosan nano microcapsules in a hydrogel layer, and respectively adhering a back lining layer and a protective film layer on two sides of the hydrogel layer to obtain the controlled-release long-acting defervescence patch.
In the invention, the hydrophilic chitosan nano microcapsule is prepared by the following method:
dispersing the hydrophilic chitosan nano microcapsule coated with the volatile essential oil in a hydrogel layer, and respectively adhering a back lining layer and a protective film layer on two sides of the hydrogel layer to obtain the controlled-release long-acting defervescence patch.
In the invention, the hydrophilic chitosan nano microcapsule coated with volatile essential oil is prepared by the following method:
dissolving hydrophilic chitosan in deionized water to prepare a chitosan aqueous solution;
dissolving volatile essential oil in an organic solvent to obtain an essential oil solution, dispersing the essential oil solution in an emulsifier aqueous solution, then uniformly mixing the essential oil solution with a chitosan aqueous solution, adjusting the pH value to carry out a re-coagulation reaction, and then spraying by adopting a coaxial nozzle to obtain the hydrophilic chitosan nano microcapsule coated with the volatile essential oil.
In the invention, the hydrophilic chitosan nano microcapsule coated with volatile essential oil is prepared by the following method:
dissolving hydrophilic chitosan in deionized water to prepare a chitosan aqueous solution; dissolving peppermint oil in ethanol to obtain a peppermint oil ethanol solution, dispersing the peppermint oil ethanol solution in a arabic gum aqueous solution, then uniformly mixing the peppermint oil ethanol solution with a chitosan aqueous solution, adjusting the pH value of the mixture to carry out a re-coagulation reaction, and then spraying the mixture by adopting a coaxial nozzle to obtain the hydrophilic chitosan nano microcapsule coated with volatile essential oil.
And then uniformly mixing the chitosan solution and adjusting the pH value to carry out a re-coagulation reaction, and further specifically, uniformly mixing the chitosan solution and adjusting the pH value to 4.0-5.5 to carry out the re-coagulation reaction.
In the present invention, the nozzle rate of the spray is 1ml/min to 15ml/min, more preferably 5 ml/min.
The air pressure of the spraying is 0.3 bar-0.5 bar;
the frequency of the spraying is 40 Hz-200 Hz.
In the invention, the mass ratio of the hydrophilic chitosan to the deionized water is 2: 50-95, more preferably 2: 75; the emulsifier is selected from Arabic gum, poloxamer 407 or decyl glucoside, and the mass ratio of the volatile essential oil to the emulsifier is 0.2: 5-10, more preferably 0.2: 6.
the antipyretic patch is simple in preparation method and easy to produce.
For a further understanding of the invention, reference will now be made in detail to the following examples.
Example 1 preparation of hydrophilic chitosan nano-microcapsules
1) Dissolving 2g of hydrophilic chitosan in 50g of deionized water, and adjusting the pH value to 2.0-3.5 to prepare a phase A;
2) uniformly dispersing 0.3g of peppermint oil into 4g of ethanol, and adding 40g of acacia gum aqueous solution with the concentration of 15% to obtain a phase B;
3) adding the phase A into the phase B, uniformly mixing, adjusting the pH value to 4.0-5.5, and carrying out a re-coagulation reaction for 60min under the condition of 500-700 rpm to obtain a peppermint oil-chitosan-Arabic gum condensate; spraying by using a B-395 coaxial nozzle, wherein the inner nozzle/outer nozzle is 450 mu m/900 mu m, the flow rate is 3mL/min, the air pressure is 300mbar, the stirring is 100%, the frequency is 70Hz, and the amplitude is 5, so that the uniform spherical hydrophilic chitosan nano microcapsule is obtained.
Example 2 static headspace method for determining slow release performance of hydrophilic chitosan nano-microcapsule
1) In the standard curve determination, 0.002g, 0.004g, 0.006g, 0.01g, 0.015g, 0.02g and 0.04g of peppermint oil and 10mL of deionized water of 0.5 percent Tween-80 are respectively put into a headspace bottle, covered, stirred forcibly in a constant-temperature water bath at 37 ℃, after balance, 0.25mL of headspace gas is taken out by an injector for gas chromatography analysis, the menthol peak is used as a content index in the chromatogram, the gas chromatography conditions are that a gas chromatograph is GC-14BPF + HSS-2B type, a chromatographic column is CBPI0.53mm × m and df is 3.0 mu m, the chromatographic conditions are that the initial temperature is 60 ℃, the temperature is kept for 3min, the temperature is 5 ℃/min is programmed to 200 ℃, the temperature is kept for 10min, the peak areas of the menthol and an internal standard substance are used as vertical coordinates, the mass concentration of the menthol is used as a horizontal coordinate, and the linear regression equation is obtained:
y＝6.995×10-5+0.142x，r＝0.9999。
the result shows that the mass concentration of the menthol is within the range of 1.0mg/ml to 5.0mg/ml, and the peak area concentration is in good linear relation.
2) And (3) measuring the hydrophilic chitosan nano microcapsule: 0.10g of hydrophilic chitosan nano-microcapsules was weighed into a dry 30mL headspace bottle containing a stirrer, 10mL of 0.5% Tween-80 in deionized water was added to the headspace bottle, and timing was started. Immediately capped, the headspace bottle was then placed in a 37 ℃ constant temperature water bath with vigorous magnetic stirring. Headspace analysis was performed at 0.5h, 1h, 2h, 4h, 6h, 8h, respectively. A0.25 mL closed gas injector was used to take out 0.25mL of headspace gas for gas chromatography. Gas chromatography conditions as in step 1).
Fig. 1 shows the release profile of peppermint oil from the hydrophilic chitosan nano-microcapsule according to the embodiment of the present invention. The result shows that the peppermint oil microencapsulation has good slow release effect, the release time is long and longer than 10h, which shows that the antipyretic patch has long duration of antipyretic effect.
EXAMPLE 3 preparation of Polymer gel
Weighing 8g of polyacrylic acid and 0.4g of dihydroxyaluminum aminoacetate into 30ml of glycerol, and uniformly mixing to obtain glycerol suspension; weighing 0.3g of tartaric acid, dissolving in 91g of deionized water, adjusting the pH to 4.0-7.0, adding into the glycerol suspension at one time, and stirring uniformly to obtain the polymer gel.
Example 4 preparation of an antipyretic patch
Weighing 8g of polyacrylic acid and 0.4g of dihydroxyaluminum aminoacetate into 30ml of glycerol, and uniformly mixing to obtain glycerol suspension; weighing 25g of the hydrophilic chitosan nano microcapsule obtained in the embodiment 1, adding the hydrophilic chitosan nano microcapsule into 91ml of tartaric acid aqueous solution containing 0.3g of tartaric acid, adjusting the pH to 4.0-7.0, adding the hydrophilic chitosan nano microcapsule into glycerol suspension at one time, uniformly stirring, filling into a mold or coating the hydrophilic chitosan nano microcapsule onto a back lining layer through a coating machine, curing, covering a protective membrane layer, cutting, and packaging to obtain the cooling patch.
Example 5
The antipyretic patch is applied to the forehead of a healthy subject meeting the conditions, the skin surface temperature of the applied part and the skin surface temperatures of other places are respectively measured at 0h, 1h, 3h, 5h, 7h and 9h by using an infrared thermometer, and the cooling effect is observed. And weighing the weight of the antipyretic patch at the time points, and observing the weight change of the antipyretic patch in the using process. The cooling test effect is shown in table 1. The results in table 1 show that the antipyretic patch has a long duration of the antipyretic effect, and when the antipyretic patch is used, the higher the body temperature is, the faster volatile essential oil in the hydrophilic chitosan nano microcapsule is released, and the antipyretic patch has the temperature sensitivity of quick response.
TABLE 1 Cooling effect of cooling paste (n is 10)
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (7)
1. A controlled release long-acting antipyretic patch, comprising: the back lining layer, the hydrogel layer and the protective film layer are arranged in sequence;
microcapsules are dispersed in the hydrogel layer, and the microcapsules are wrapped with volatile essential oil;
the microcapsule is a hydrophilic chitosan nano microcapsule which can be dissolved in deionized water;
the particle size of the hydrophilic chitosan nano microcapsule is 200-1000 nm, and the mass ratio of the hydrophilic chitosan nano microcapsule to the hydrogel layer is 10-20: 70-80 parts;
the hydrophilic chitosan nano microcapsule coated with volatile essential oil is prepared by the following method:
dissolving hydrophilic chitosan in deionized water to prepare a chitosan aqueous solution;
dissolving volatile essential oil in an organic solvent to obtain an essential oil solution, dispersing the essential oil solution in an emulsifier aqueous solution, then uniformly mixing the essential oil solution with the chitosan aqueous solution, adjusting the pH value of the mixture to carry out a re-coagulation reaction, and then spraying by adopting a coaxial nozzle to obtain the hydrophilic chitosan nano microcapsule coated with the volatile essential oil;
when the cooling patch is used, the higher the body temperature of a patient is, the higher the speed of converting the bound water in the hydrogel layer into free water is, so that the volatile essential oil in the hydrophilic chitosan nano microcapsule is released more quickly, and the cooling patch has the temperature sensitivity of quick response.
2. The controlled-release long-acting antipyretic patch according to claim 1, wherein the volatile essential oil comprises one or more of peppermint oil, pine root oil, lemon essential oil and eucalyptus essential oil.
3. The controlled-release long-acting antipyretic patch according to claim 1, wherein the hydrogel layer is prepared from a polymer gel;
the high-molecular gel comprises a high-molecular polymer, a humectant, a cross-linking agent and a cross-linking regulator.
4. The controlled-release long-acting antipyretic patch as claimed in claim 3, wherein the mass ratio of the high molecular polymer to the humectant to the cross-linking agent to the cross-linking regulator is 15-30: 10-30: 0.01-2: 0.05 to 0.5.
5. The controlled-release long-acting antipyretic patch according to claim 1, wherein the nozzle velocity of the spray is 1ml/min to 15 ml/min.
6. The controlled-release long-acting antipyretic patch according to claim 5, wherein the air pressure of the spray is 0.3bar to 0.5 bar;
the frequency of the spraying is 40 Hz-200 Hz.
7. The preparation method of the controlled-release long-acting antipyretic patch as claimed in any one of claims 1 to 6, which is characterized by comprising the following steps:
dispersing the hydrophilic chitosan nano microcapsule coated with the volatile essential oil in a hydrogel layer, and respectively adhering a back lining layer and a protective film layer on two sides of the hydrogel layer to obtain the controlled-release long-acting defervescence patch.
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| CN116966224B (en) * | 2023-04-27 | 2024-03-19 | 广东省时珍本草科学研究院 | Preparation method of silver Hu Ganmao antipyretic external preparation |
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