Acupuncture point ironing moxibustion patch packing material for promoting drug release and preparation method of acupuncture point ironing moxibustion patch packing material

Abstract

The invention relates to an acupoint ironing moxibustion patch packing material for promoting drug release and a preparation method thereof, and belongs to the technical field of heating material preparation, the acupoint ironing moxibustion patch packing material comprises a heating layer, a patch placement layer and a bonding layer, the heating layer comprises a polymer base material, a heat conduction filler, a temperature buffer material and a self-heating material; wherein the temperature buffer material is prepared by mixing a reaction product of polyethylene glycol and triphenylmethane triisocyanate with a phase change microcapsule. Polyethylene glycol reacts with triphenylmethane triisocyanate to generate carbamate bonds, and heat conduction and temperature regulation and control can be achieved at the same time in combination with the phase change microcapsules. According to the technical scheme, the problems of temperature control and drug effect persistence of traditional acupoint application are solved through the temperature buffer material and the interlayer composite technology.

Description

Technical Field

[0001] The present application relates to the technical field of preparation of heat - generating materials, and more specifically, it relates to a packagings material for acupoint ironing and moxibustion patch for promoting drug release and a preparation method thereof. Background Art

[0002] Short stature is a relatively common growth and development disorder in childhood, with many influencing factors. According to clinical manifestations, it can be classified into the category of "five delays and five flaccidities". In the Western medicine field, the method is to administer recombinant growth hormone treatment, but growth hormone needs to be injected subcutaneously every day and is expensive. In the traditional Chinese medicine field, the method of syndrome differentiation and treatment is mainly adopted. Among them, Compound Eugenia Jambolana Fruit Stomach - regulating Patch is an acupoint application composed of traditional Chinese medicines such as Eugenia Jambolana Fruit, Atractylodes Lancea, Atractylodes Macrocephala, Amomum kravanh, Amomum villosum, Aucklandia Lappa, etc., and its functions are to invigorate the spleen and promote digestion, dry dampness and regulate the middle - energizer, regulate qi and promote qi movement. By promoting the application effect of Compound Eugenia Jambolana Fruit Stomach - regulating Patch on the Shenque acupoint and Shenzhu acupoint, the symptoms of short stature can be conditioned.

[0003] In the existing technology, most ironing and moxibustion patches rely on external heat sources or chemical heating packs, but lack a dynamic temperature control mechanism. For example, the heat generated by the iron powder oxidation reaction is easily affected by environmental temperature and humidity, resulting in a local temperature fluctuation range of up to ±10°C, which may cause skin burns. The packagings material plays a key role in promoting drug release of acupoint ironing and moxibustion patches. Traditional packagings materials such as cotton cloth and non - woven fabric have low thermal conductivity, cannot evenly disperse heat, and are prone to form "hot spots" or "cold zones", resulting in uneven distribution of drug effects. Research shows that when the temperature deviation exceeds 5°C, the activity of drug molecules decreases significantly, resulting in a decline in the drug effect.

[0004] Based on the above statements, the present application provides a packagings material for acupoint ironing and moxibustion patch for promoting drug release and a preparation method thereof. Summary of the Invention

[0005] In order to solve the problems raised in the background art, the present application provides a packagings material for acupoint ironing and moxibustion patch for promoting drug release and a preparation method thereof. The technical solution of the present invention solves the problems of temperature control and drug action persistence of traditional acupoint application through a temperature - buffer material and an interlayer composite process.

[0006] The present application provides a packagings material for acupoint ironing and moxibustion patch for promoting drug release and a preparation method thereof, adopting the following technical solutions:

[0007] A packagings material for acupoint ironing and moxibustion patch for promoting drug release, comprising a heat - generating layer, a patch - placing layer and an adhesive layer. The materials in the heat - generating layer include a polymer substrate, a heat - conducting filler, a temperature - buffer material and a self - heating material; wherein, the temperature - buffer material is prepared by mixing the reaction product of polyethylene glycol and triphenylmethane triisocyanate with phase - change microcapsules.

[0008] Further, the temperature - buffer material is prepared by the following steps:

[0009] A1, adding polyethylene glycol, a catalyst and triphenylmethane triisocyanate to a solvent, stirring for 10-20 minutes, raising the system temperature to 60-65°C, reacting for 5-8 hours and raising the reaction temperature to 80-85°C at a heating rate of 1-5°C / min, and continuing the reaction for 1-2 hours to prepare a carbamate product;

[0010] A2. Mix the carbamate product obtained in step A1 and the phase change microcapsules to obtain a temperature buffer material.

[0011] Further preferably, the temperature buffer material is prepared by the following steps:

[0012] A1. Polyethylene glycol, a catalyst and triphenylmethane triisocyanate are added to a 5 wt % toluene solution at a mass volume ratio of 1 g: (5-10) mL, and stirred at a rate of 30-90 rpm for 10-20 minutes. The system temperature is raised to 60-65° C. in an inert atmosphere. After reacting for 5-8 hours, the reaction temperature is raised to 80-85° C. at a heating rate of 1-5° C. / min. The reaction is continued for 1-2 hours to prepare a carbamate product.

[0013] In the above reaction process, dibutyltin acetate acts as a Lewis acid catalyst to activate the isocyanate group by taking away the lone pair of electrons of the nitrogen atom of triphenylmethane triisocyanate (TTI for short). Subsequently, the hydroxyl group in the polyethylene glycol molecule carries out a nucleophilic attack on the activated isocyanate group to generate a carbamate bond, thereby obtaining a carbamate product.

[0014] A2. Mix the carbamate product obtained in step A1 and the phase change microcapsules to obtain a temperature buffer material.

[0015] Preferably, the inert gas flow rate is set to 40-50 mL / min.

[0016] Furthermore, in step A1, the molecular weight of the polyethylene glycol used is 2000-5000Da.

[0017] Furthermore, in step A1, the molar ratio of polyethylene glycol, catalyst and triphenylmethane triisocyanate is (8-10):5:(0.4-0.6).

[0018] Furthermore, in step A2, the mass ratio of the carbamate product and the phase change microcapsule is (2-4):(5-8).

[0019] Furthermore, the polymer substrate in the heating layer is a PU adhesive.

[0020] Furthermore, the thermally conductive filler is at least one of metal nanopowders.

[0021] Further, the self-heating material is obtained by mixing iron powder and zinc oxide in a mass ratio of (90-95):(5-10).

[0022] Among the above components, by adding zinc oxide, over-oxidation of iron powder to produce trace amounts of rust is prevented, and an appropriate amount of zinc oxide is used as an oxidation protection agent.

[0023] Further, the mass ratio of the polymer substrate, the heat-conducting filler, the temperature buffer material, and the self-heating material is (5-7):(6-8):(18-22):(60-70).

[0024] A preparation method of a package material for a drug-promoting acupoint moxibustion patch specifically includes the following steps:

[0025] The polymer substrate, the heat-conducting filler, the temperature buffer material, and the self-heating material are encapsulated using a non-woven fabric bag and freeze-dried to obtain a heating layer; the acupoint moxibustion patch is placed into the non-woven fabric bag to obtain a patch placement layer; an adhesive is coated between the two layers, and the heat-insulating layer coated with the adhesive is thermocompression-bonded with the heating layer to sequentially form a heating layer, an adhesive layer, and a patch placement layer, thus obtaining a package material for a drug-promoting acupoint moxibustion patch.

[0026] Further, the conditions for freeze-drying are: freeze-drying for 2-4 hours at a temperature of -20 to -30 °C under a vacuum of 10-30 mbar.

[0027] Further, the adhesive used is an acrylate adhesive, and the coating amount of the adhesive is 2-5 g / m 2 .

[0028] Further, the parameters for thermocompression bonding are a pressure of 5-10 MPa, a temperature of 80-120 °C, and a pressure-holding time of 5-10 minutes.

[0029] In summary, the present application has the following beneficial effects:

[0030] In the technical solution of the present invention, by regulating the reaction of polyethylene glycol and TTI to prepare carbamic acid products, by setting two parts of temperature gradients, at a temperature of 60-65 °C and under the action of a catalyst, a linear carbamate chain is generated; subsequently, the temperature is increased, so that the π-π stacking effect dominates in the system, and the TTI molecule contains three benzene rings and has a strong π-electron system; moreover, the benzene rings and carbonyl groups contained in the carbamate esterification product can also participate in π-π interactions. The high temperature enhances the molecular thermal motion, improves the diffusivity and collision frequency of the system, and promotes the dynamic reorganization of π-π stacking in the system, so that a cross-linked structure product formed by hydrogen bonds and π-π stacking of the linear carbamate chain and the TTI benzene ring structure is generated in the system. Subsequently, in the process of preparing the finished product of the ironing moxibustion patch packaging material, through freeze-drying, the cross-linked product structure is promoted to form an aerogel morphology. The temperature buffer material contains linear carbamate chains and aerogel particles. The molecular orientation of the linear carbamate chains forms a heat conduction channel, which promotes the uniform diffusion of heat from the heat source (i.e., the Fe powder oxidation reaction) to the surrounding, and improves the temperature uniformity; the components of the aerogel particles can reduce local overheating through the "microenvironment heat retention" effect and play a better temperature buffer effect. The prepared acupoint ironing moxibustion patch packaging material can continuously release heat through the iron powder self-heating material, and cooperate with the phase change microcapsules of the temperature buffer material to slowly release heat energy, so as to achieve a long-term warm effect, reduce the need for frequent replacement, and improve the treatment persistence. Detailed implementation mode

[0031] The following will combine the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative efforts belong to the scope of protection of the present invention.

[0032] The reagents involved in the specific implementation mode of this application are all analytical grades. In addition:

[0033] The phase change microcapsules are provided by Hefei Ruixue New Materials Technology Co., Ltd., and the phase change temperature is 45 °C.

[0034] Iron powder: Reduced iron powder, with an average particle size of 10-44 μm.

[0035] Zinc oxide: The average particle size is 1-5 μm.

[0036] Metal nanopowder: Nano-aluminum nitride powder, with an average particle size of 10-50 nm.

[0037] Acrylate adhesive: Bostik 7371.

[0038] Example 1

[0039] A drug release-promoting acupoint moxibustion patch packaging material, comprising a heating layer, a patch placement layer and an adhesive layer, wherein the materials in the heating layer include a polymer substrate, a heat-conducting filler, a temperature buffer material and a self-heating material;

[0040] Among them, the temperature buffer material is prepared by the following steps:

[0041] A1. Polyethylene glycol, a catalyst and triphenylmethane triisocyanate are added to a 5 wt% toluene solution according to a mass-volume ratio of 1 g:5 mL, stirred at a rate of 30 rpm for 10 minutes, then the system temperature is raised to 60 °C under a nitrogen atmosphere, and after reacting for 5 hours, the reaction temperature is raised to 80 °C at a heating rate of 3 °C / minute, and after continuing to react for 1 hour, a urethane product is prepared; during the process, the nitrogen gas flow rate is set to 40 mL / min, the molecular weight of the polyethylene glycol used is 2000 Da, and the molar ratio of polyethylene glycol, catalyst, and triphenylmethane triisocyanate is 8:5:0.4;

[0042] A2. The urethane product obtained in step A1 is mixed with phase change microcapsules to obtain a temperature buffer material; among them, the mass ratio of the urethane product to the phase change microcapsules is 2:5.

[0043] Among them, the mass ratio of the polymer substrate, the heat-conducting filler, the temperature buffer material and the self-heating material is 5:6:18:60; the polymer substrate is a PU adhesive, the heat-conducting filler is metal nano powder, and the self-heating material is obtained by mixing iron powder and zinc oxide according to a mass ratio of 95:5.

[0044] The preparation method of the aforementioned acupoint moxibustion patch packaging material specifically includes the following steps:

[0045] The polymer substrate, the heat-conducting filler, the temperature buffer material and the self-heating material are encapsulated in a non-woven bag, and freeze-dried at a temperature of -20 °C for 3 hours under a vacuum of 10 mbar to obtain a heating layer; the acupoint moxibustion patch is put into a non-woven bag to obtain a patch placement layer; an adhesive is coated between the two layers, and the heat-insulating layer coated with the adhesive is thermocompression-bonded with the heating layer. The parameters of the thermocompression bonding are a pressure of 5 MPa, a temperature of 90 °C, and a pressure-holding time of 10 minutes, successively forming a heating layer, an adhesive layer and a patch placement layer, thus obtaining a drug release-promoting acupoint moxibustion patch packaging material; among them, the adhesive used is an acrylate adhesive, and the adhesive coating amount is 3 g / m 2 .

[0046] Example 2

[0047] A drug release-promoting acupoint moxibustion patch packaging material, comprising a heating layer, a patch placement layer and an adhesive layer, wherein the materials in the heating layer include a polymer substrate, a heat-conducting filler, a temperature buffer material and a self-heating material;

[0048] Among them, the temperature buffer material is prepared by the following steps:

[0049] A1. Polyethylene glycol, a catalyst, and triphenylmethane triisocyanate are added to a 5 wt% toluene solution according to a mass-to-volume ratio of 1 g:8 mL. After stirring at a rate of 60 rpm for 15 minutes, the temperature of the system is raised to 62°C under a nitrogen atmosphere. After reacting for 6 hours, the reaction temperature is raised to 83°C at a heating rate of 3°C / minute, and after continuing to react for 1 hour, a urethane product is prepared; during the process, the nitrogen gas flow rate is set to 45 mL / min, the molecular weight of the polyethylene glycol used is 3000 Da, and the molar ratio of polyethylene glycol, catalyst, and triphenylmethane triisocyanate is 9:5:0.5;

[0050] A2. The urethane product obtained in step A1 and the phase change microcapsules are mixed to obtain the temperature buffer material; among them, the mass ratio of the urethane product to the phase change microcapsules is 3:7.

[0051] Among them, the mass ratio of the polymer substrate, the heat-conducting filler, the temperature buffer material, and the self-heating material is 6:7:20:65; the polymer substrate is a PU adhesive, the heat-conducting filler is metal nano-powder, and the self-heating material is obtained by mixing iron powder and zinc oxide according to a mass ratio of 93:7.

[0052] The preparation method of the aforementioned acupoint moxibustion patch packaging material specifically includes the following steps:

[0053] The polymer substrate, the heat-conducting filler, the temperature buffer material, and the self-heating material are encapsulated using a non-woven fabric bag. Under a vacuum of 20 mbar, freeze-drying is carried out at a temperature of -30°C for 3 hours to obtain a heating layer; the acupoint moxibustion patch is put into a non-woven fabric bag to obtain a patch placement layer; an adhesive is coated between the two layers, and the heat-insulating layer coated with the adhesive is thermocompression-bonded with the heating layer. The parameters of the thermocompression bonding are a pressure of 10 MPa, a temperature of 100°C, and a pressure-holding time of 8 minutes, successively forming a heating layer, a bonding layer, and a patch placement layer, thus obtaining an acupoint moxibustion patch packaging material for promoting drug release; among them, the adhesive used is an acrylate adhesive, and the adhesive coating amount is 4 g / m 2 .

[0054] Example 3

[0055] An acupoint moxibustion patch packaging material for promoting drug release, comprising a heating layer, a patch placement layer, and a bonding layer. The materials in the heating layer include a polymer substrate, a heat-conducting filler, a temperature buffer material, and a self-heating material;

[0056] Among them, the temperature buffer material is prepared by the following steps:

[0057] A1. Polyethylene glycol, a catalyst, and triphenylmethane triisocyanate were added to a 5 wt% toluene solution at a mass-to-volume ratio of 1 g:10 mL. After stirring at a rate of 90 rpm for 20 minutes, the system temperature was raised to 65 °C under a nitrogen atmosphere. After reacting for 8 hours, the reaction temperature was raised to 85 °C at a heating rate of 5 °C / minute, and after continuing to react for 2 hours, a urethane product was prepared; during the process, the nitrogen gas flow rate was set to 50 mL / min, the molecular weight of the polyethylene glycol used was 4000 Da, and the molar ratio of polyethylene glycol, catalyst, and triphenylmethane triisocyanate was 10:5:0.6;

[0058] A2. The urethane product obtained in step A1 was mixed with phase change microcapsules to obtain a temperature buffer material; among them, the mass ratio of the urethane product to the phase change microcapsules was 4:8.

[0059] Among them, the mass ratio of the polymer substrate, heat-conducting filler, temperature buffer material, and self-heating material is 7:8:22:70; the polymer substrate is a PU adhesive, the heat-conducting filler is metal nano-powder, and the self-heating material is obtained by mixing iron powder and zinc oxide in a mass ratio of 92:8.

[0060] The preparation method of the aforementioned acupoint moxibustion patch packaging material specifically includes the following steps:

[0061] The polymer substrate, heat-conducting filler, temperature buffer material, and self-heating material were encapsulated using a non-woven bag and freeze-dried at a temperature of -30 °C for 3 hours under a vacuum of 30 mbar to obtain a heating layer; the acupoint moxibustion patch was placed in a non-woven bag to obtain a patch placement layer; an adhesive was coated between the two layers, and the heat-insulating layer coated with the adhesive was thermocompression-bonded to the heating layer. The parameters of the thermocompression bonding were a pressure of 10 MPa, a temperature of 120 °C, and a pressure-holding time of 10 minutes, successively forming a heating layer, a bonding layer, and a patch placement layer, thus obtaining a drug-release-promoting acupoint moxibustion patch packaging material; among them, the adhesive used was an acrylate adhesive, and the coating amount of the adhesive was 5 g / m 2 。

[0062] Comparative Example 1

[0063] The difference between this comparative example and Example 1 is that in step A2, the mass ratio of the urethane product to the phase change microcapsules is 2:10.

[0064] Comparative Example 2

[0065] The difference between this comparative example and Example 1 is that in step A1, the reaction conditions of polyethylene glycol, catalyst, and triphenylmethane triisocyanate are: the system temperature was raised to 80 °C under a nitrogen atmosphere, and after reacting for 6 hours, a urethane product was prepared.

[0066] Comparative Example 3

[0067] The difference between this comparative example and Example 1 is that in step A1, the reaction conditions of polyethylene glycol, catalyst and triphenylmethane triisocyanate are as follows: the system temperature is raised to 60 °C under a nitrogen atmosphere, and after reacting for 6 hours, a urethane product is prepared.

[0068] Comparative Example 4

[0069] The difference between this comparative example and Example 1 is that the materials in the heat - generating layer of this comparative example include a polymer substrate, a heat - conducting filler and a self - heating material, and their mass ratio is 5:24:60.

[0070] Performance Test

[0071] Now, performance tests are carried out on the acupoint moxibustion patch packages prepared in Examples 1 - 3 and Comparative Examples 1 - 4 of this application.

[0072] Temperature buffering performance test: The latent heat of phase change values of samples in different groups are measured by using differential scanning calorimetry. Samples with a weight of 10 mg ± 0.1 mg are taken in each group, and the temperature is raised to 120 °C at a heating rate of 10 °C / min to measure the latent heat of phase change. Each group of samples is measured 5 times, and the average value is recorded.

[0073] Thermal conductivity test: The samples in different groups are compacted in a press, and the unified sample thickness is 2 mm. Subsequently, the thermal conductivity of the heat - generating layer materials of samples in different groups is measured at room temperature. Each group of samples is measured 5 times, and the average value is recorded.

[0074] Heat - generating performance test: The heat - release time, average heating rate and maximum temperature of samples in different groups are tested in an incubator to judge the heat - generating effect of the samples. The temperature of the incubator is set at 30 °C, the sample mass is controlled at 50 g, and the test ends when the final temperature reaches 30 °C.

[0075] The specific performance test results are shown in Table 1 below:

[0076] Table 1

[0077]

[0078] As can be seen from the results shown in Table 1 above:

[0079] The comprehensive performance of the acupoint ironing moxibustion patch packaging materials prepared in Examples 1-3 of this application is significantly better than that of the samples prepared in the comparative examples. From the results of Comparative Example 1, it can be seen that due to the relatively high usage amount of the phase change material, the proportion of the buffer material decreases, the latent heat value of the prepared sample increases, but the thermal conductivity decreases, and the comprehensive heat generation performance decreases. From the results of Comparative Example 2, it can be seen that when the urethane product is prepared by reaction at 80 °C, the π-π interaction dominates in the system. After subsequent freeze-drying treatment, the content of aerogel particles in the system increases greatly, resulting in a decrease in thermal conductivity. For the test results of Comparative Example 3, the reaction is carried out at a lower temperature, which can increase the content of linear urethane products in the system compared with Example 1, and the heat transfer rate is too fast, resulting in too high a maximum temperature. From the results of Comparative Example 4, it can be seen that the lack of a temperature buffer layer results in local overheating phenomena.

[0080] In the description of the specification, the description with reference to terms such as "one embodiment", "example", "specific example", etc. means that the specific features, structures, materials or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic expressions of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in a suitable manner in any one or more embodiments or examples.

[0081] The above content is only an example and illustration of the present invention. Those skilled in the art of this technology can make various modifications or supplements to the described specific embodiments or use similar methods to replace them, as long as they do not deviate from the invention or exceed the scope defined by the claims of this patent, they should all fall within the protection scope of the present invention.

Claims

1. A packaging material for acupoint hot-pressing and moxibustion patch for promoting drug release, characterized in that: It includes a heating layer, a patch placement layer and an adhesive layer, wherein the materials in the heating layer include a polymer substrate, a thermal conductive filler, a temperature buffer material and a self-heating material; The temperature buffer material is prepared by mixing the reaction product of polyethylene glycol and triphenylmethane triisocyanate with phase change microcapsules.

2. The acupoint ironing and moxibustion patch packaging material for promoting drug release according to claim 1, characterized in that: The temperature buffer material is prepared by the following steps: A1, adding polyethylene glycol, a catalyst and triphenylmethane triisocyanate to a solvent, stirring for 10-20 minutes, raising the system temperature to 60-65°C, reacting for 5-8 hours and raising the reaction temperature to 80-85°C at a heating rate of 1-5°C / min, and continuing the reaction for 1-2 hours to prepare a carbamate product; A2. Mix the carbamate product obtained in step A1 and the phase change microcapsules to obtain a temperature buffer material.

3. The acupoint ironing and moxibustion patch packaging material for promoting drug release according to claim 2, characterized in that: In step A1, the molar ratio of polyethylene glycol, catalyst and triphenylmethane triisocyanate is (8-10):5:(0.4-0.6).

4. The acupoint ironing and moxibustion patch packaging material for promoting drug release according to claim 2, characterized in that: In step A2, the mass ratio of the carbamate product and the phase change microcapsules is (2-4):(5-8).

5. The acupoint ironing and moxibustion patch packaging material for promoting drug release according to claim 1, characterized in that: The thermally conductive filler is at least one of metal nanopowders.

6. The acupoint hot-pressing and moxibustion patch packaging material for promoting drug release according to claim 1, characterized in that: The self-heating material is obtained by mixing iron powder and zinc oxide in a mass ratio of (90-95):(5-10).

7. The acupoint ironing and moxibustion patch packaging material for promoting drug release according to claim 1, characterized in that: The mass ratio of the polymer matrix, the thermal conductive filler, the temperature buffer material and the self-heating material is (5-7):(6-8):(18-22):(60-70).

8. A method for preparing a packaging material for acupoint hot-pressing and moxibustion patch for promoting drug release as claimed in any one of claims 1 to 7, characterized in that: The specific steps include: The polymer substrate, thermal conductive filler, temperature buffer material and self-heating material are packaged in a non-woven bag and freeze-dried to obtain a heating layer; the acupoint hot moxibustion patch is placed in the non-woven bag to obtain a patch placement layer; an adhesive is coated between the two layers, and the heat preservation layer coated with the adhesive is hot-pressed and composited with the heating layer to form a heating layer, an adhesive layer and a patch placement layer in sequence, thereby obtaining an acupoint hot moxibustion patch packaging material for promoting drug release.

9. The method for preparing a drug release-promoting acupoint hot-moxibustion patch packaging material according to claim 8, characterized in that: The coating amount of adhesive used is 2-5g / m 2 .

10. The method for preparing a packaging material for acupoint hot-pressing and moxibustion patch for promoting drug release according to claim 8, characterized in that: The parameters of hot pressing compound are pressure 5-10MPa, temperature 80-120℃, and holding time 5-10 minutes.

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