Preparation method of dumbbell array storage type hollow bacterial cellulose hydrogel transdermal patch
The dumbbell array storage hollow bacterial cellulose hydrogel transdermal patch synthesized by bacterial interface self-assembly mediated by PDMS sponge mold solves the problems of high rigidity and easy wrinkling and delamination of bacterial cellulose membranes in the prior art, and achieves the effects of efficient drug loading and long-term sustained release.
Patent Information
- Application Number
- CN202511848090.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-09
- Publication Date
- 2026-01-16
AI Technical Summary
Existing bacterial cellulose membranes are thick and rigid, making it difficult to meet the requirements for skin adhesion. They are prone to wrinkling and delamination, and have a small drug loading capacity, making it difficult to achieve efficient drug loading and long-term sustained release.
A dumbbell array storage hollow bacterial cellulose hydrogel transdermal patch was synthesized by using a polydimethylsiloxane (PDMS) sponge mold to mediate the self-assembly of bacteria at the bacterial interface. The PDMS sponge mold floats on the surface of the bacterial solution, mediating the orderly synthesis of bacterial cellulose and forming a double-layer, hollow structure.
It achieves efficient drug loading and long-term sustained release, excellent breathability, and a simple and economical preparation process, making it suitable for individualized production in various scenarios and meeting the needs of skin adhesion.
Smart Images
Figure CN121337632A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the fields of polymer materials and biomanufacturing technology, and in particular to a method for preparing a dumbbell array storage type hollow bacterial cellulose hydrogel transdermal patch. Background Technology
[0002] Bacterial cellulose is a cellulose hydrogel produced by microbial fermentation. It possesses a fine nanofiber structure and various excellent properties, such as strong water retention, excellent mechanical properties, and high biocompatibility, making it a rising star in transdermal patch substrate research. However, bacterial cellulose films obtained through simple fermentation are only about 1.5 cm thick, requiring slicing of the raw material. Furthermore, its high crystallinity makes the cellulose quite rigid, severely impacting its extensibility and making it difficult to meet skin adhesion requirements, easily causing wrinkling and delamination, resulting in discomfort. Therefore, environmentally friendly transdermal patches with high storability and excellent adhesion remain scarce. Summary of the Invention
[0003] In view of the above-mentioned defects or deficiencies in the prior art, it is desirable to provide a method for preparing a dumbbell array storage type hollow bacterial cellulose hydrogel transdermal patch, which is synthesized by bacterial interface self-assembly mediated by polydimethylsiloxane (PDMS) sponge mold. The transdermal patch can efficiently load drugs, provide long-term sustained release, conformal adhesion, and has excellent air permeability.
[0004] The present invention provides a method for preparing a dumbbell array storage type hollow bacterial cellulose hydrogel transdermal patch, comprising the following steps: 1) Mix the basic components of PDMS with the curing agent evenly to obtain solution A; 2) Add an organic solvent to solution A and mix thoroughly to obtain solution B; 3) Add ultrapure water to solution B and stir until homogeneous to form a PDMS emulsion; 4) Place the mold with the perforated dumbbell pattern array flat at the bottom of the container, then pour the PDMS emulsion into the container, let it stand for a period of time, heat it to solidify, remove it and take off the mold to obtain the solidified material; remove the organic solvent and water from the solidified material to obtain the PDMS sponge mold; 5) After statically culturing the PDMS sponge mold with the pattern facing down on the bacterial solution, peel off the PDMS sponge mold to obtain a bacterial cellulose hydrogel transdermal patch; 6) The bacterial cellulose hydrogel transdermal patch was boiled in NaOH solution, cooled to room temperature, and then the NaOH solution was replaced with deionized water until the pH was neutral to obtain a dumbbell array storage type hollow bacterial cellulose hydrogel transdermal patch.
[0005] Furthermore, based on the total mass of the PDMS emulsion as 100%, the mass percentage of solution A is 6-19%, the mass percentage of organic solvent is 3.8-13%, and the mass percentage of ultrapure water is 74-83%; the organic solvent is liquid silicone oil or paraffin oil.
[0006] Furthermore, in step 4), the mold is formed by laser engraving of an acrylic sheet or a glass sheet, with a laser engraving intensity of 5%-45%, a laser engraving speed of 10-200mm / s, a thickness of 2.0-5.0mm for the acrylic sheet or glass sheet, and a laser engraving depth of 1.0-4.0mm. The thickness of the PDMS emulsion poured onto the mold is 1-2 cm; the standing temperature is 20-25℃, the standing time is 4-10 h, the heating curing temperature is 60-75℃, and the heating curing time is 4-6 h.
[0007] Furthermore, the width of the perforated dumbbell pattern on the mold is 0.5-1.5mm, the length is 2.0-4.0mm, and the radius of the dumbbell circle is 0.8-2.5mm; with the total area of the mold being 100%, the total area of the perforated dumbbell pattern accounts for 43%-69%.
[0008] Furthermore, in step 4), the density of the PDMS sponge mold is less than that of the bacterial solution, causing it to float on the surface of the bacterial solution, with its upper surface in contact with the air. The hydrophobicity of the PDMS sponge mold allows it to be shaped by the bacterial solution it contacts, and its porosity promotes gas exchange. The PDMS sponge mold is placed in the bacterial solution for 1-7 days for static culture, during which bacterial cellulose hydrogel grows on its lower surface. The PDMS sponge mold is then peeled off to obtain a hollow, double-layered bacterial cellulose hydrogel transdermal patch.
[0009] Furthermore, in step 5), the thickness of the single-layer film of the bacterial cellulose membrane grown on the lower surface of the PDMS sponge mold is 10-50 μm, and the overall thickness is 1-4 mm. The microorganisms that can produce bacterial cellulose in the bacterial solution are selected from one of the genera *Acetobacter*, *Agrobacterium*, *Pseudomonas*, *Nitrogenobacter*, *Rhizobium*, or *Cladophora*.
[0010] Furthermore, in step 6), the hollow layers of the dumbbell array storage type hollow bacterial cellulose hydrogel transdermal patch are interconnected.
[0011] In addition, the present invention also provides a dumbbell array storage type hollow bacterial cellulose hydrogel transdermal patch prepared by the above-described method.
[0012] In addition, the present invention also provides an application of the dumbbell array storage type hollow bacterial cellulose hydrogel transdermal patch as described above in the loading of hydrophilic and hydrophobic essences and medicines, skin care, health care, and disease treatment.
[0013] In addition, the present invention also provides a PDMS sponge mold obtained during the preparation process of the dumbbell array storage type hollow bacterial cellulose hydrogel transdermal patch as described above.
[0014] Compared with the prior art, the beneficial effects of the present invention are: (1) This invention prepares a PDMS emulsion with high fluidity and replication ability, which can replicate fine structures. The PDMS sponge mold prepared by it has high hydrophobicity and air permeability, and can provide sufficient gas exchange capacity. The PDMS sponge mold floats on the surface of the bacterial solution and can mediate the orderly synthesis of bacteria on its surface, promoting the secretion and synthesis of bacterial cellulose, resulting in a double-layered, hollow bacterial cellulose membrane. The bacterial cellulose membrane synthesized in situ by the PDMS mold has high shape fidelity and high bacterial cellulose yield.
[0015] (2) The preparation method of the present invention uses readily available raw materials, has a simple and efficient process, is economical and environmentally friendly, and the size, number of arrays and thickness of hollow layer of dumbbell pattern can be adjusted to meet the needs of different scenarios. Its dumbbell shape can effectively lock in liquid, prevent liquid flow, and achieve efficient drug loading.
[0016] (3) The transdermal patch prepared by the present invention has a large drug loading capacity, thin single layer thickness, good adhesion, long sustained release time and individualized production. It can be used for loading and sustained release of various solutions and has great application value in facial care, health care and disease treatment.
[0017] It should be understood that the description in the Summary of the Invention is not intended to limit the key or essential features of the embodiments of the present invention, nor is it intended to restrict the scope of the invention. Other features of the invention will become readily apparent from the following description. Attached Figure Description
[0018] Other features, objects, and advantages of the invention will become more apparent from the following detailed description of non-limiting embodiments with reference to the accompanying drawings: Figure 1 Flowchart for the preparation of bacterial cellulose hydrogel transdermal patches; Figure 2 A schematic diagram of the structure of a bacterial cellulose hydrogel transdermal patch; Figure 3 Electron micrographs of the dense and loose layers of the bacterial cellulose hydrogel transdermal patch in Example 1; Figure 4Figure a1 is a schematic diagram of the single-layer membrane in Comparative Example 1, and Figure a2 is an effect diagram of liquid storage inside the single-layer membrane; Figure b1 is a schematic diagram of the hollow bacterial cellulose hydrogel transdermal patch in Comparative Example 2, and Figure b2 is an effect diagram of liquid storage inside the hollow bacterial cellulose hydrogel transdermal patch; Figure c1 is a schematic diagram of the dumbbell array storage type hollow bacterial cellulose hydrogel transdermal patch in Example 1, and Figure c2 is an effect diagram of liquid storage inside the dumbbell array storage type hollow bacterial cellulose hydrogel transdermal patch. Detailed Implementation
[0019] The present invention will now be described in further detail with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and not intended to limit it. Furthermore, it should be noted that, for ease of description, only the parts relevant to the invention are shown in the accompanying drawings.
[0020] It should be noted that, unless otherwise specified, the embodiments and features described in the present invention can be combined with each other. The present invention will now be described in detail with reference to the accompanying drawings and embodiments.
[0021] Example 1
[0022] like Figures 1-3 As shown, the preparation method of the dumbbell array storage type hollow bacterial cellulose hydrogel transdermal patch includes the following steps: 1) Acrylic mold preparation: Use a laser engraving machine to engrave a dumbbell array on an acrylic sheet according to the design. Then cut out the engraved pattern to form a perforated dumbbell pattern array, which is used as a positive mold. The laser engraving intensity is 5%-45%, the engraving speed is 10-200mm / s, and the preferred template is an acrylic sheet of 2.0-5.0mm, with an engraving depth of 1.0-4.0mm. 2) Preparation of PDMS sponge mold: Weigh the basic components of PDMS (Dow Corning Sylgard 184) using an analytical balance according to a mass ratio of 5:7.5:35: paraffin oil: ultrapure water; first, stir the basic components of PDMS and the curing agent with a glass rod, then add the paraffin oil and stir well, and finally add the ultrapure water dropwise to make a PDMS emulsion. Then pour the PDMS emulsion into a container containing an acrylic mold and let it stand at room temperature for 4-10 hours; then place it in a 60-75℃ oven and heat to cure for 4-6 hours, and then demold to obtain the cured material. Ultrasonize with anhydrous ethanol in an ultrasonic machine for 30-60 minutes, then wash with pure water, and finally place it in a 60-80℃ oven for 30-60 minutes; repeat the above steps until no white substance appears after cleaning or no oil stains are left after drying and wiping with paper, to obtain the PDMS sponge mold; 3) Preparation of dumbbell array storage-type hollow bacterial cellulose transdermal patch: A PDMS sponge mold was placed on a stainless steel tray, wrapped, and then sterilized under high temperature and pressure (115℃, 30 min), followed by low-temperature drying (65℃, 4 h). The PDMS sponge mold was placed on the floating surface of inoculated HS bacterial solution (inoculum:HS medium = 1:14), and then incubated in a 30℃ incubator for 1-7 days to obtain the formed bacterial cellulose hydrogel. The prepared bacterial cellulose hydrogel was boiled twice in 0.1% NaOH solution for 20 minutes each time. Finally, the film was rinsed with deionized water until the pH was neutral to obtain the dumbbell array storage-type hollow bacterial cellulose transdermal patch.
[0023] PDMS sponge molds can reverse-copy patterns prepared by laser engraving machines, with structural precision at the micrometer level.
[0024] Comparative Example 1:
[0025] The preparation of a single-layer membrane includes the following steps: 1) Acrylic mold preparation: Same as in Example 1; 2) Preparation of bacterial cellulose transdermal patches: An acrylic mold was placed on a stainless steel tray, wrapped, sterilized, and dried at low temperature (65℃, 4h). Freshly prepared bacterial solution (inoculum:HS medium = 1:14) was added to the acrylic mold. The mold was then incubated at 30℃ for 1-7 days to obtain a formed bacterial cellulose hydrogel film. The prepared bacterial cellulose film was boiled twice in 0.1% NaOH solution for 20min each time; finally, the film was rinsed with deionized water until the pH was neutral to obtain the bacterial cellulose transdermal patch. Comparative Example 2:
[0026] Preparation of hollow bacterial cellulose hydrogel transdermal patches includes the following steps: 1) Acrylic mold preparation: Compared with Example 1, the mold in Comparative Example 2 did not have the perforated dumbbell pattern array; 2) PDMS sponge mold preparation: Same as in Example 1; 3) Preparation of hollow bacterial cellulose transdermal patch: Same as in Example 1.
[0027] In this application, the bacterial strain in the bacterial solution is Acetobacter xylinum, strain number ATCC23767, purchased from the Guangdong Provincial Center for Microbial Culture Collection; the preparation method of this application can prepare transdermal patches of various shapes as needed, such as nasal patches, eye patches, neck patches, knee patches, lip patches, forehead patches, or palm patches, etc.
[0028] like Figure 4As shown, taking the production of face masks as an example, the single-layer mask prepared in Comparative Example 1 has a small amount of liquid stored; the hollow bacterial cellulose hydrogel transdermal patch prepared in Comparative Example 2 has a large amount of liquid stored, but the liquid inside is very easy to flow and accumulate, resulting in poor performance; the dumbbell array storage type hollow bacterial cellulose hydrogel transdermal patch prepared in Example 1 has a large amount of liquid stored inside and the liquid is evenly distributed, effectively solving the technical problems of poor thickness controllability, high hardness, small load capacity, and easy wrinkling when naturally fermenting and synthesizing bacterial cellulose membranes in the prior art.
[0029] In the description of this specification, the terms "one embodiment," "some embodiments," etc., refer to specific features, structures, materials, or characteristics described in connection with that embodiment or example, which are included in at least one embodiment or example of this application. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.
[0030] The above are merely preferred embodiments of this application and are not intended to limit this application. Various modifications and variations can be made to this application by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the protection scope of this application.
Claims
1. A method for preparing a dumbbell array reservoir type hollow bacterial cellulose hydrogel transdermal patch, characterized in that, The method comprises the following steps: 1) uniformly mixing basic components of PDMS with a curing agent to obtain solution A; 2) adding an organic solvent to the solution A, and uniformly mixing to obtain solution B; 3) adding ultrapure water to the solution B, and uniformly stirring to form a PDMS emulsion; 4) placing a mold with a perforated dumbbell pattern array on the bottom of a container, pouring the PDMS emulsion into the container, and after standing for a period of time, heating and curing, removing the mold to obtain a cured product, and removing the organic solvent and moisture in the cured product to obtain a PDMS sponge mold; 5) floating the PDMS sponge mold with the pattern downward on a bacterial solution for static culture, and then tearing off the PDMS sponge mold to obtain a bacterial cellulose hydrogel transdermal patch; 6) placing the bacterial cellulose hydrogel transdermal patch in a NaOH solution for boiling, cooling to room temperature, and replacing the NaOH solution with deionized water to neutralize the pH to obtain a dumbbell array storage type hollow bacterial cellulose hydrogel transdermal patch.
2. The preparation method of the dumbbell array reservoir-type hollow bacterial cellulose hydrogel transdermal patch according to claim 1, characterized in that, In terms of the total mass of the PDMS emulsion, the mass percentage of solution A is 6-19%, the mass percentage of the organic solvent is 3.8-13%, and the mass percentage of ultrapure water is 74-83%; the organic solvent is liquid silicone oil or paraffin oil.
3. The preparation method of the dumbbell array reservoir-type hollow bacterial cellulose hydrogel transdermal patch according to claim 1, characterized in that, In the step 4), the mold is an acrylic plate or a glass plate processed by laser engraving, the laser engraving strength is 5%-45%, the laser engraving speed is 10-200 mm / s, the thickness of the acrylic plate or the glass plate is 2.0-5.0 mm, and the laser engraving depth is 1.0-4.0 mm; The thickness of the PDMS emulsion poured on the mold is 1-2 cm; the standing temperature is 20-25℃, the standing time is 4-10 h, the heating and curing temperature is 60-75℃, and the heating and curing time is 4-6 h.
4. The method for preparing the dumbbell array storage type hollow bacterial cellulose hydrogel transdermal patch according to claim 1, characterized in that, The middle width of the perforated dumbbell pattern on the mold is 0.5-1.5 mm, the length is 2.0-4.0 mm, and the dumbbell circular radius is 0.8-2.5 mm; in terms of the total area of the mold, the total area of the perforated dumbbell pattern accounts for 43%-69%.
5. The method for preparing the dumbbell array storage type hollow bacterial cellulose hydrogel transdermal patch according to claim 1, characterized in that, In the step 4), the density of the PDMS sponge mold is less than that of the bacterial solution, so that it floats on the surface of the bacterial solution and the upper surface is in contact with air; The hydrophobicity of the PDMS sponge mold can shape the contacted bacterial solution, and the porosity can promote gas exchange; the PDMS sponge mold is statically cultured in the bacterial solution for 1-7 days, and the bacterial cellulose hydrogel grows on the lower surface; 6. The method for preparing the dumbbell array storage type hollow bacterial cellulose hydrogel transdermal patch according to claim 1, characterized in that, In the step 5), the single-layer film thickness of the bacterial cellulose film grown on the lower surface of the PDMS sponge mold is 10-50 μm, and the overall thickness is 1-4 mm; The microorganism capable of producing bacterial cellulose in the bacterial solution is selected from one of Acetobacter, Agrobacterium, Pseudomonas, Azotobacter, Rhizobium or Cladophora.
7. The method for preparing the dumbbell array storage type hollow bacterial cellulose hydrogel transdermal patch according to claim 1, characterized in that, In the step 6), the hollow layers of the dumbbell array storage type hollow bacterial cellulose hydrogel transdermal patch are interconnected.
8. A dumbbell array storage type hollow bacterial cellulose hydrogel transdermal patch prepared by the preparation method of the dumbbell array storage type hollow bacterial cellulose hydrogel transdermal patch according to any one of claims 1-7.
9. Application of the dumbbell array storage type hollow bacterial cellulose hydrogel transdermal patch according to claim 8 in loading of hydrophilic and hydrophobic essence, medicine, skin care, health care, and disease treatment.
10. A PDMS sponge mold obtained in the preparation process of the preparation method of the dumbbell array storage type hollow bacterial cellulose hydrogel transdermal patch according to any one of claims 1-7.