CN114176892B - Constant-temperature heating device for transdermal drug delivery and preparation process thereof - Google Patents
Constant-temperature heating device for transdermal drug delivery and preparation process thereof Download PDFInfo
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- 238000010438 heat treatment Methods 0.000 title claims abstract description 118
- 238000013271 transdermal drug delivery Methods 0.000 title claims abstract description 22
- 238000002360 preparation method Methods 0.000 title claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 76
- 239000000463 material Substances 0.000 claims abstract description 52
- 239000011630 iodine Substances 0.000 claims abstract description 28
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 28
- 238000009423 ventilation Methods 0.000 claims abstract description 25
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical group [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims abstract description 23
- 239000000843 powder Substances 0.000 claims abstract description 14
- 239000002994 raw material Substances 0.000 claims abstract description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims abstract description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229910001868 water Inorganic materials 0.000 claims abstract description 11
- 229910052902 vermiculite Inorganic materials 0.000 claims abstract description 9
- 235000019354 vermiculite Nutrition 0.000 claims abstract description 9
- 239000010455 vermiculite Substances 0.000 claims abstract description 9
- 239000011347 resin Substances 0.000 claims abstract description 8
- 229920005989 resin Polymers 0.000 claims abstract description 8
- 239000002250 absorbent Substances 0.000 claims abstract description 6
- 239000011780 sodium chloride Substances 0.000 claims abstract description 6
- 238000002156 mixing Methods 0.000 claims abstract description 5
- 238000007789 sealing Methods 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 9
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 239000004698 Polyethylene Substances 0.000 claims description 6
- 238000011049 filling Methods 0.000 claims description 6
- 238000005520 cutting process Methods 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 238000009740 moulding (composite fabrication) Methods 0.000 claims description 3
- 239000004745 nonwoven fabric Substances 0.000 claims description 3
- -1 polyethylene Polymers 0.000 claims description 3
- 229920000573 polyethylene Polymers 0.000 claims description 3
- 238000004321 preservation Methods 0.000 claims description 3
- 238000007493 shaping process Methods 0.000 claims description 3
- 238000005303 weighing Methods 0.000 claims description 3
- 239000012528 membrane Substances 0.000 claims 1
- 238000004080 punching Methods 0.000 abstract description 11
- 229910052742 iron Inorganic materials 0.000 abstract description 4
- 238000005516 engineering process Methods 0.000 abstract description 3
- 239000003814 drug Substances 0.000 description 15
- 239000000126 substance Substances 0.000 description 13
- 230000000694 effects Effects 0.000 description 12
- 239000004744 fabric Substances 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 9
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 9
- 230000000052 comparative effect Effects 0.000 description 8
- 229960001193 diclofenac sodium Drugs 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000001186 cumulative effect Effects 0.000 description 5
- 229960002373 loxoprofen Drugs 0.000 description 5
- WORCCYVLMMTGFR-UHFFFAOYSA-M loxoprofen sodium Chemical compound [Na+].C1=CC(C(C([O-])=O)C)=CC=C1CC1C(=O)CCC1 WORCCYVLMMTGFR-UHFFFAOYSA-M 0.000 description 5
- 239000004820 Pressure-sensitive adhesive Substances 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 230000020169 heat generation Effects 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
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- 206010020843 Hyperthermia Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 206010049816 Muscle tightness Diseases 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
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- 230000003197 catalytic effect Effects 0.000 description 1
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- 238000013270 controlled release Methods 0.000 description 1
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- 238000001514 detection method Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000005485 electric heating Methods 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 238000004146 energy storage Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000010096 film blowing Methods 0.000 description 1
- 238000003958 fumigation Methods 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 230000036031 hyperthermia Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 238000010409 ironing Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229940066974 medicated patch Drugs 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
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- 238000006386 neutralization reaction Methods 0.000 description 1
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- 238000004806 packaging method and process Methods 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 238000004663 powder metallurgy Methods 0.000 description 1
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- 210000004872 soft tissue Anatomy 0.000 description 1
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- 238000006467 substitution reaction Methods 0.000 description 1
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- 230000002277 temperature effect Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
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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
- A61F7/03—Compresses or poultices for effecting heating or cooling thermophore, i.e. self-heating, e.g. using a chemical reaction
- A61F7/032—Compresses or poultices for effecting heating or cooling thermophore, i.e. self-heating, e.g. using a chemical reaction using oxygen from the air, e.g. pocket-stoves
- A61F7/034—Flameless
-
- 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
- A61F7/0241—Apparatus for the preparation of hot packs, hot compresses, cooling pads, e.g. heaters or refrigerators
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K5/00—Heat-transfer, heat-exchange or heat-storage materials, e.g. refrigerants; Materials for the production of heat or cold by chemical reactions other than by combustion
- C09K5/16—Materials undergoing chemical reactions when used
-
- 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
- A61F2007/0225—Compresses or poultices for effecting heating or cooling connected to the body or a part thereof
- A61F2007/0226—Compresses or poultices for effecting heating or cooling connected to the body or a part thereof adhesive, self-sticking
-
- 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
- A61F2007/0244—Compresses or poultices for effecting heating or cooling with layers
-
- 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
- A61F2007/0261—Compresses or poultices for effecting heating or cooling medicated
-
- 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
- A61F7/03—Compresses or poultices for effecting heating or cooling thermophore, i.e. self-heating, e.g. using a chemical reaction
- A61F7/032—Compresses or poultices for effecting heating or cooling thermophore, i.e. self-heating, e.g. using a chemical reaction using oxygen from the air, e.g. pocket-stoves
- A61F7/034—Flameless
- A61F2007/036—Fuels
- A61F2007/038—Carbon or charcoal, e.g. active
-
- 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
- A61M2037/0007—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin having means for enhancing the permeation of substances through the epidermis, e.g. using suction or depression, electric or magnetic fields, sound waves or chemical agents
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Physics & Mathematics (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Thermal Sciences (AREA)
- Public Health (AREA)
- Vascular Medicine (AREA)
- Thermotherapy And Cooling Therapy Devices (AREA)
- Medical Informatics (AREA)
- Anesthesiology (AREA)
- Hematology (AREA)
- Dermatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Combustion & Propulsion (AREA)
- Materials Engineering (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Emergency Medicine (AREA)
Abstract
The invention discloses a constant-temperature heating device for transdermal drug delivery, which comprises an upper wrapping layer, a perforated film layer, a breathable film layer, a heating layer, a non-breathable film layer and a lower wrapping layer which are sequentially arranged from top to bottom, wherein the raw materials of the heating layer are secondary reduced iron powder, activated carbon, water, vermiculite, sodium chloride and water-absorbent resin, and the activated carbon is formed by mixing low-iodine-value activated carbon and high-iodine-value activated carbon in proportion. The bag is convenient to carry and rapid in heating, and solves the problem that the punching film falls down into a bag and the problems that the ventilation amount of the ventilation film is small and the bag is easy to expand by adopting the technology of combining the ventilation film with the punching film; by adopting the method of proportionally mixing the low-iodine value activated carbon and the high-iodine value activated carbon, the heating material layer has high heating speed and long heating time, and is matched with secondary reduced iron powder with the iron content of more than 95 percent, so that the heating time is greatly improved.
Description
Technical Field
The invention belongs to the technical field of medical supplies, and particularly relates to a constant-temperature heating device for transdermal drug delivery and a preparation process thereof.
Background
The hot ironing is to heat the medicine or other matter, wrap the medicine or other matter with cloth, and then rub and massage the affected part. The heat treatment method is easy to operate, and can adjust medicines or other substances according to the needs of the illness, has small side effects and obvious local treatment effect, so that the application is wide. The heat energy stored after the medicine is heated can transfer the heat energy and the medicine to the body through the skin during massage. The warm therapy can reduce pain caused by muscle tension decrease and muscle spasm, improve blood circulation and lymphatic circulation, and accelerate inflammation dissipation.
The heat treatment device can continuously supply heat for a period of time to ensure the treatment effect, and the temperature requirement of the heat treatment cannot be too low or too high. Experimental study shows that when the hyperthermia temperature is lower than 45 ℃, the effect is not obvious, and the ideal treatment effect is not achieved; when the heat treatment temperature is higher than 50 ℃, the treatment effect is weak, and the skin is likely to be burnt; and the optimal curative effect can be obtained only when the temperature of the thermal therapy is controlled between 43 and 45 ℃. The traditional physiotherapy heat sources such as fumigation, washing, hot compress and the like are inconvenient to prepare, the average temperature losing time is within 1-1.5 hours, the holding time is short, the temperature is difficult to control, and the traditional physiotherapy heat sources cannot meet the high-efficiency and convenient requirements of the current society.
The heating devices which can be used for human bodies and are researched and developed at home and abroad can be summarized into five types according to heat generation modes, namely an electric heating material, a phase change heating material, a moisture absorption heating material, a photo-thermal material and a chemical heating material. The chemical heating material generates heat through exothermic reaction of chemical substances as a heat source to heat, has the advantages of high energy storage density and low cost, and the starting substances are daily available substances such as oxygen, water and the like, do not need electricity, fire and any other energy sources to automatically generate heat, so that the use is very convenient. The chemical heat generating agent is a formula mixture taking exothermic chemical reaction through a scientific formula as a heat source, and is mainly divided into two types: one type is a solid chemical exothermic agent, namely metal powder (aluminum, iron, magnesium, etc.) and oxygen contact oxidation exothermic; one type is a liquid chemical exothermic agent, such as inorganic salt hydration exotherm, acid moisture absorption, alkali dissolution, acid-base neutralization, and the like. The chemical heat generating agent formula is an important factor influencing the highest temperature of a heat generating material, the self-heating product of which is composed of iron powder, water and a catalyst component is taken as a research object in the prior document 'temperature control of the self-heating product', and the optimal proportion of the raw materials is 59% of the iron powder, 22% of the water and 19% of the catalyst component through researching three performance indexes of heating time, highest temperature and duration, wherein the optimal proportion of the catalyst component is 4% of active carbon, 3% of sodium chloride, 0.5% of a super-absorbent material and 11.5% of vermiculite, the purity of elemental iron in the iron powder is more than 89%, and the temperature performance is best when the mesh number is 80-200.
At present, the domestic research on heating devices is mainly to control the temperature by adjusting the chemical heating agent formula, and the related research on the surface coating material structure and the water controlled release performance to control the exothermic reaction rate is less. Although the chemical heat generator formula directly affects the heating time, the highest temperature and the duration of the heat generating device, the raw materials and the processing technological parameters in the formula also have great influence on the temperature performance of the product, and on the basis of the known chemical heat generator formula, the heat generating device on the market still frequently generates the phenomena of overhigh temperature, overhigh temperature and uneven heat generation. For example: the prior heating device adopts a perforated film ventilation mode to control the temperature of the heating device, the production process of the perforated film adopts mechanical perforation generally, and the falling bag is easy to be caused in the use process, so that the heating temperature of the heating device is uneven. Although the PE breathable film can also be subjected to breathable control, the PE breathable film is limited by the production technology (film blowing method and casting method), the pore size of the PE breathable film is not easy to control, and the constant temperature control of a heating device is not facilitated.
Disclosure of Invention
Based on the defects of the prior art, the invention aims to provide a constant temperature heating device for transdermal drug delivery, oxygen intake is controlled through a double-layer ventilation structure of a perforated film layer and a ventilation film layer, and proper oxidation reaction speed and strength are achieved by matching with a heating material layer, so that a constant temperature effect is obtained; the invention also discloses a preparation process of the constant-temperature heating device, and the performance of each raw material of the constant-temperature heating device is ensured by controlling process parameters.
In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:
a constant temperature heating device for transdermal drug delivery comprises an upper wrapping layer, a perforated film layer, a breathable film layer, a heating material layer, a non-breathable film layer and a lower wrapping layer which are sequentially arranged from top to bottom;
the heating material layer is prepared from the following raw materials in percentage by mass:
the activated carbon is formed by mixing low-iodine value activated carbon and high-iodine value activated carbon according to a mass ratio of 1:0.8-1.2, wherein the low-iodine value activated carbon is the activated carbon with the iodine value of 350-500 mg/g, and the high-iodine value activated carbon is the activated carbon with the iodine value of 700-1300 mg/g.
Preferably, the upper wrapping layer and the lower wrapping layer are both made of non-woven fabrics.
Preferably, the breathable film layer and the non-breathable film layer are made of polyethylene materials.
Preferably, the perforated film layer is uniformly provided with a plurality of ventilation holes at intervals, the aperture of the ventilation holes is 0.3-1.5 mm, and the hole spacing is 3-6 mm.
Preferably, the ventilation rate of the ventilation film layer is 300-500 g/m 2 ·24h。
Preferably, the granularity of the secondary reduced iron powder is 80-120 meshes, the granularity of the activated carbon is 250-350 meshes, the granularity of the vermiculite is 70-100 meshes, and the granularity of the water-absorbing resin is 30-50 meshes.
The preparation process of the constant temperature heating device for transdermal drug delivery comprises the following steps:
(1) Weighing all raw materials of the heating material layer according to mass percent; dissolving sodium chloride in water, adding water-absorbent resin, and stirring uniformly to obtain a material A; uniformly stirring secondary reduced iron powder, activated carbon and vermiculite in vacuum to obtain a material B; adding the material A into the material B, uniformly stirring in vacuum, bagging, sealing, and standing for 12-24 hours;
(2) Stacking a lower wrapping layer, a non-breathable film layer, a perforated film layer and an upper wrapping layer in sequence from bottom to top, uniformly filling the product obtained in the step (1) between the non-breathable film layer and the breathable film layer at intervals, heat-sealing and shaping, forming a plurality of sub-cavities between the breathable film layer and the non-breathable film layer after heat sealing, and filling the heating material layer in the sub-cavities;
(3) And (5) die cutting to remove redundant materials, thus obtaining the product.
Preferably, the constant temperature heating device is packaged and sealed or placed in a vacuum box for preservation.
When the constant temperature heating device is used, air passes through the upper wrapping layer, and sequentially passes through the high-ventilation perforated film layer and the low-ventilation breathable film layer to enter the heating material layer, so that the oxygen absorption reaction starts to generate heat, negative pressure is generated between the breathable film layer and the non-breathable film layer, the air is tightly absorbed on two sides of the heating material layer, and constant temperature heating is ensured. The invention has the advantages of easily available raw materials, convenient carrying and rapid heating, solves the problem that the punching film falls down into a bag by adopting the technology of combining the ventilation film with the punching film, and also solves the problems of small ventilation amount and easy bag expansion of the ventilation film; by adopting the method of proportionally mixing the low-iodine value activated carbon and the high-iodine value activated carbon, the heating material layer has high heating speed and long heating time, and is matched with secondary reduced iron powder with the iron content of more than 95 percent, so that the heating time is greatly improved.
Drawings
FIG. 1 is a schematic view showing the structure of a constant temperature heating apparatus for transdermal drug delivery according to examples 1 to 4;
FIG. 2 is a schematic diagram showing the structure of a thermostatic heat device according to example 1 used in combination with a transdermal drug delivery system for non-steroidal anti-inflammatory drugs;
FIG. 3 is an in vitro cumulative transdermal amount of diclofenac sodium patch (nunununude mouse back skin) at different temperature conditions;
FIG. 4 is the in vitro cumulative transdermal amount of diclofenac sodium patch (Ba Ma Xiaoxiang pig back skin) at different temperature conditions;
FIG. 5 is the in vitro cumulative transdermal amounts of loxoprofen sodium patch (Ba Ma Xiaoxiang pig back skin) at different temperature conditions;
FIG. 6 is a schematic view showing the structure of a constant temperature heat generating device for transdermal drug delivery according to example 5;
FIG. 7 is a schematic diagram showing the structure of a thermostatic heat device according to example 5 used in combination with a non-steroidal anti-inflammatory drug transdermal drug delivery system;
FIG. 8 is a top view of FIG. 7;
fig. 9 is a schematic view of the structure of the upper cladding layer of example 6.
Detailed Description
In order to make the technical objects, technical solutions and advantageous effects of the present invention more apparent, the technical solutions of the present invention will be further described with reference to specific examples, which are intended to illustrate the present invention but are not to be construed as limiting the present invention, and specific techniques or conditions are not specified in the examples, and are performed according to techniques or conditions described in the literature in the art or according to the product specifications.
The raw materials used for the heating material layer in the following examples are all common commercial products. Wherein the secondary reduced iron powder is purchased from a powder metallurgy factory (common partner) of Xin powder of Qinggan, a consolidated city, and the granularity is 100 meshes; the activated carbon is purchased from Shanxi carbon element environmental protection Co., ltd, the low-iodine value activated carbon has an iodine value of 400mg/g and a granularity of 300 meshes, and the high-iodine value activated carbon has an iodine value of 800mg/g and a granularity of 300 meshes; the vermiculite is purchased from Alzhuyun limited company of Lingshu county, and the granularity is 80 meshes; the granularity of the water-absorbing resin is 40 meshes. In addition, the upper wrapping layer and the lower wrapping layer are both made of non-woven fabrics, and the weight of each square meter is about 60g; the breathable film layer and the non-breathable film layer are made of polyethylene materials, and the weight of each square meter is about 40g; the breathable film layer had a breathable content of about 350g/m 2 24h; the punching film layer adopts machinery to punch, evenly arranges the punching needle along circumferencial direction interval on the roller for punching, and the punching needle is toper and the bottom surface diameter of punching needle is 1.5mm, interval be 4 x 4mm.
Examples 1 to 4
A constant temperature heating device for transdermal drug delivery, as shown in fig. 1, comprises an upper wrapping layer 101, a perforated film layer 102, a breathable film layer 103, a heating material layer 104, a non-breathable film layer 105 and a lower wrapping layer 106 which are sequentially arranged from top to bottom, wherein edges of the upper wrapping layer 101, the perforated film layer 102, the breathable film layer 103, the non-breathable film layer 105 and the lower wrapping layer 106 are pressed together, and the heating material layer 104 is filled between the breathable film layer 103 and the non-breathable film layer 105.
The proportions of the respective raw materials used for the heat generating material layer 104 described in examples 1 to 4 are shown in table 1.
TABLE 1 weight percent of the raw materials of the heating layer 104 (wt%)
The preparation process of the constant temperature heating device for transdermal drug delivery comprises the following steps:
(1) Weighing the raw materials of the heating material layer 104 according to the mass percentage; dissolving sodium chloride in water, adding water-absorbent resin, and stirring uniformly to obtain a material A; uniformly stirring secondary reduced iron powder, activated carbon and vermiculite in vacuum to obtain a material B; adding the material A into the material B, uniformly stirring in vacuum, bagging, sealing, and standing for 24 hours;
(2) Stacking a lower wrapping layer 106, a non-breathable film layer 105, a breathable film layer 103, a perforated film layer 102 and an upper wrapping layer 101 in sequence from bottom to top, uniformly filling the product obtained in the step (1) between the non-breathable film layer 105 and the breathable film layer 103 at intervals, performing heat sealing and shaping, forming a plurality of sub-cavities between the breathable film layer 103 and the non-breathable film layer 105 after heat sealing, and filling the heating material layer 104 (30 g) into the sub-cavities;
(3) And (5) die cutting to remove redundant materials, thus obtaining the product.
The constant temperature heating device is packaged and sealed or placed in a vacuum box for preservation.
In order to examine the effect of the constant temperature heating device applied to transdermal drug delivery of the nonsteroidal anti-inflammatory drug, the constant temperature heating device prepared in the embodiment 1 is combined with a transdermal drug delivery system of the nonsteroidal anti-inflammatory drug, and two realization modes are provided, wherein one structure is shown in fig. 2, the constant temperature heating device 1, the elastic cloth 2, the drug-containing patch 3 and the release paper 4 are sequentially arranged from top to bottom, pressure sensitive adhesives are coated on two sides of the elastic cloth 2, the constant temperature heating device 1 is adhered to the upper side of the elastic cloth 2 through the pressure sensitive adhesives, and the drug-containing patch 3 is adhered to the lower side of the elastic cloth 2 through the pressure sensitive adhesives; another structure is to directly bond the constant temperature heating device 1 and the medicine-containing patch 3 together. Before use, the packaging and sealing or vacuum storage are needed; when in use, the package is opened, the release paper 4 is torn, and the medicine-containing patch 3 is adhered to the skin surface. The patch 3 used herein is a commercially available diclofenac sodium patch (Nohua pharmaceutical (Japan), lot number 210030) and a loxoprofen sodium patch (Lide chemical Co., ltd., japan), lot number N070R), respectively.
First, the transdermal rate and transdermal amount of the medicated patch 3 were examined under normal temperature (without using the isothermal heating device 1) and heating (using the isothermal heating device 1) conditions using Franz (Franz) diffusion Chi Fa, using knoop mouse back skin and ba Ma Xiaoxiang pig back skin, respectively. The in vitro accumulated transdermal quantity results of the diclofenac sodium patch under different temperature conditions are shown in figure 3 by taking the back skin of a female knoop mouse for 6-7 weeks as a test object, and the in vitro transmission quantity of the diclofenac sodium under the heating condition is about 1.5 times of the transmission quantity under the normal temperature condition at 24 hours. The results of the in vitro cumulative transdermal amounts of diclofenac sodium patches under different temperature conditions are shown in fig. 4, with the back skin of a pig of 1 month bar Ma Xiaoxiang as the test subject, and the in vitro transdermal amounts of diclofenac sodium under heating conditions at 24 hours are about 1.9 times the transdermal amounts under normal temperature conditions. The results of the in vitro cumulative transdermal amounts of loxoprofen sodium patch under different temperature conditions are shown in fig. 5, using the back skin of a pig of 1 month bar Ma Xiaoxiang as a test object, and the in vitro transdermal amount of loxoprofen sodium under heating conditions is about 2.3 times of the transdermal amount under normal temperature conditions at 24 hours.
Next, by measuring the content of the drug in the residue after the use of the transdermal drug delivery system of the non-steroidal anti-inflammatory drug, the amount of the drug entering the skin and blood of the human body under the conditions of normal temperature (without using the constant temperature heating device 1) and heating (using the constant temperature heating device 1) of the transdermal drug delivery system of the non-steroidal anti-inflammatory drug was compared, and the application time was 12 hours, and the test results are shown in table 3.
Table 2 skin transdermal quantity of constant temperature heating device
As can be seen from Table 2, after the constant temperature heating device 1 was added, the transdermal amounts of human skin of diclofenac sodium and loxoprofen sodium were increased by about 23% and 30%, respectively.
In summary, the constant temperature heating device 1 prepared by the invention is used for transdermal administration of non-steroidal anti-inflammatory drugs, can promote the transdermal rate and the transdermal quantity of the non-steroidal anti-inflammatory drugs, improves the bioavailability and the clinical curative effect of the drugs, and is used for treating various muscle, soft tissues and joint moderate pains.
Example 5
A constant temperature heating device for transdermal drug delivery, as shown in fig. 6, comprises an upper layer structure and a lower layer structure, wherein a heating material layer 104 is uniformly arranged between the upper layer structure and the lower layer structure at intervals. The upper layer structure comprises an upper wrapping layer 101, a perforated film layer 102 and a breathable film layer 103 which are sequentially arranged from top to bottom, the lower layer structure comprises a non-breathable film layer 105 and a lower wrapping layer 106 positioned below the non-breathable film layer 105, the upper wrapping layer 101, the perforated film layer 102, the breathable film layer 103, the non-breathable film layer 105 and the lower wrapping layer 106 are heat-sealed and pressed, a plurality of sub-inner cavities (in a grid shape) are formed between the breathable film layer 103 and the non-breathable film layer 105, and the heating material layer 104 is filled in the sub-inner cavities.
The constant temperature heat generating device of example 5 can be prepared according to the process of example 1, except that: the subchamber of example 5 is smaller and a constant temperature heating device is provided with a plurality of subchambers for accommodating the heating layers 104, and adjacent heating layers 104 are separated by a superstructure and a substructure that are pressed together. Compared with the embodiment 1 (the heating material layer 104 is integrally arranged), the constant temperature heating device of the embodiment 5 has better flexibility, is easy to bend and can be better applied to all joint parts of a body.
The constant temperature heating device and the non-steroidal anti-inflammatory drug transdermal drug delivery system in the embodiment 5 are combined, the structure is shown in fig. 7 and 8, the constant temperature heating device 1, the elastic cloth 2, the drug-containing patch 3 and the release paper 4 are sequentially arranged from top to bottom, the elastic cloth 2 is I-shaped, and the constant temperature heating device 1 and the drug-containing patch 3 are respectively adhered to the upper side and the lower side of the elastic cloth 2 through pressure sensitive adhesives. When in use, the package is opened, the release paper 4 is torn, and the elastic cloth 2 and the medicine-containing patch 3 are adhered to the skin surface.
Example 6
In order to further improve the softness and the application effect of the constant temperature heating device, as shown in fig. 9, the upper wrapping layer 101 is pre-compressed and folded, that is, on the basis of example 5: the upper wrapping layer 101 comprises a body 1011, wherein folding parts 1012 are uniformly arranged on the body 1011 at intervals along the longitudinal direction, the folding parts 1012 are formed by folding the body 1011 to the left side or the right side, and the number of the folding parts 1012 is required to ensure that at least one folding part 1012 is arranged above each heating material layer 104, so that when the constant temperature heating device is bent downwards, the folding parts 1012 can be properly opened, the extension length of the upper wrapping layer 101 is increased, and the bending degree of the constant temperature heating device is improved. The constant temperature heating device guarantees the compaction of the heating material layer 104 through the punching film layer 102, the ventilation film layer 103, the non-ventilation film layer 105 and the lower wrapping layer 106, when in use, the lower wrapping layer 106 is an inner layer, the upper wrapping layer 101 is an outer layer, and the punching film layer 102, the ventilation film layer 103 and the non-ventilation film layer 105 with good toughness are matched with the extensible upper wrapping layer 101, so that the constant temperature heating device is better in application property, and is not easy to fall off or tilt during bending.
Comparative example 1
According to the technical scheme of the constant temperature heating device in the embodiment 1, the difference is that: the activated carbon is low-iodine value activated carbon.
Comparative example 2
According to the technical scheme of the constant temperature heating device in the embodiment 1, the difference is that: the active carbon is all high-iodine value active carbon.
Comparative example 3
According to the technical scheme of the constant temperature heating device in the embodiment 1, the difference is that: the perforated film layer 102 is removed and only the breathable film layer 105 is used.
The heat generating performance of the constant temperature heat generating devices manufactured in examples 1 to 4 and comparative examples 1 to 3 was measured according to the temperature test method of the pharmaceutical industry standard YY0060-2018 of the people's republic of China. The time required for starting oxidizing heat generation until the temperature rises to 40 ℃ is taken as the heating time, the total value of the holding time of the heat generation temperature above 40 ℃ is taken as the duration time, and the time of the highest temperature in the duration time and the average temperature above 40 ℃ is taken as the temperature guarantee time. 8 parallel samples are made for each group of constant temperature heating devices, and the average value is obtained after the highest value and the lowest value are removed.
The temperature test shows that the comparative example 3 is expanded in the detection process, and the temperature curve is greatly changed after the temperature is increased to 40 ℃, so that the constant temperature cannot be maintained; the other examples and comparative examples did not suffer from the swelling problem, and the temperature test results are shown in table 2.
Table 3 results of temperature test of constant temperature heating device
As can be seen from Table 3, the constant temperature heating device prepared by the invention has the heating time length of less than 10min, the heating time length of more than 13h and the highest temperature of 50+/-2 ℃. In the comparative example 1, the activated carbon with low iodine value is adopted, the temperature rising speed is high, but the duration time is short; comparative example 2 uses high iodine value activated carbon, which has slow temperature rising speed but long duration; the invention uses the low-iodine value active carbon and the high-iodine value active carbon, which not only has higher heating speed, but also can greatly prolong the heating time. In addition, from the temperature test results, it can be deduced that: in the raw materials of the heating material layer 104, water is used as an oxide participating in the reaction, the heating time can be prolonged, but excessive water can influence the heating temperature; the active carbon has a catalytic effect on constant-temperature heating, and can influence the heating time and temperature; the secondary reduced iron powder has a micro-adjusting effect on the highest temperature, and the highest temperature can be improved by properly increasing the amount of the secondary reduced iron powder.
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and not for limiting the same; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some or all of the technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit of the invention.
Claims (4)
1. A constant temperature heating device for transdermal drug delivery, characterized in that: comprises an upper wrapping layer, a perforation film layer, a ventilation film layer, a heating material layer, a non-ventilation film layer and a lower wrapping layer which are sequentially arranged from top to bottom;
the heating material layer is prepared from the following raw materials in percentage by mass:
50-75% of secondary reduced iron powder,
5-25% of active carbon,
15-30% of water,
5-15% of vermiculite,
1-5% of sodium chloride,
3-10% of a water-absorbent resin;
the activated carbon is formed by mixing low-iodine value activated carbon and high-iodine value activated carbon according to a mass ratio of 1:0.8-1.2, wherein the low-iodine value activated carbon is the activated carbon with the iodine value of 350-500 mg/g, and the high-iodine value activated carbon is the activated carbon with the iodine value of 700-1300 mg/g;
the upper wrapping layer and the lower wrapping layer are both made of non-woven fabrics; the breathable film layer and the non-breathable film layer are made of polyethylene materials; the perforated membrane layer is uniformly provided with a plurality of ventilation holes at intervals, the aperture of the ventilation holes is 0.3-1.5 mm, and the hole spacing is 3-6 mm; the ventilation quantity of the ventilation film layer is 300-500 g/m 2 ·24 h。
2. A constant temperature heat generating device for transdermal administration according to claim 1, wherein: the granularity of the secondary reduced iron powder is 80-120 meshes, the granularity of the activated carbon is 250-350 meshes, the granularity of the vermiculite is 70-100 meshes, and the granularity of the water-absorbing resin is 30-50 meshes.
3. The process for preparing a thermostatic heat generating device for transdermal drug delivery according to claim 1 or 2, comprising the steps of:
(1) Weighing all raw materials of the heating material layer according to mass percent; dissolving sodium chloride in water, adding water-absorbent resin, and stirring uniformly to obtain a material A; uniformly stirring secondary reduced iron powder, activated carbon and vermiculite in vacuum to obtain a material B; adding the material A into the material B, uniformly stirring in vacuum, bagging, sealing, and standing for 12-24 hours;
(2) Stacking a lower wrapping layer, a non-breathable film layer, a perforated film layer and an upper wrapping layer in sequence from bottom to top, uniformly filling the product obtained in the step (1) between the non-breathable film layer and the breathable film layer at intervals, heat-sealing and shaping, forming a plurality of sub-cavities between the breathable film layer and the non-breathable film layer after heat sealing, and filling the heating material layer in the sub-cavities;
(3) And (5) die cutting to remove redundant materials, thus obtaining the product.
4. A process for the preparation of a thermostatic heat generating device for transdermal drug delivery according to claim 3, wherein: the constant temperature heating device is packaged and sealed or placed in a vacuum box for preservation.
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| CN102715978A (en) * | 2012-07-10 | 2012-10-10 | 甘肃省化工研究院 | Self-heated type thermal paste |
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| KR20030046110A (en) * | 2001-12-05 | 2003-06-12 | 고명진 | Far infrared rays radiating and heat generating cataplasma |
| CN1760310A (en) * | 2004-10-13 | 2006-04-19 | 上海超迪科技有限公司 | Chemic exothermic material and exothermic bag |
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