A method of preparing a composite hydrogel dressing

Abstract

The application discloses a preparation method of a composite hydrogel dressing, and is characterized by comprising the following step A1. raw material preparation: 20-40 parts of Astragalus membranaceus, 10-20 parts of Atractylodes macrocephala, 10-20 parts of Angelica sinensis, 5-15 parts of Carthamus tinctorius, 3-10 parts of dragon's blood, and 5-15 parts of Bai Zhi. The prepared composite hydrogel dressing has the characteristics of softness and hydrophilicity, can be closely attached to a wound surface of various shapes, and can well cover a flat wound surface or an irregular wound surface, so that a moist healing environment is provided for the wound surface. The moist environment is favorable for the proliferation and migration of wound cells, promotes wound healing, and can also reduce pain during dressing change. The dried hydrogel can form a porous sponge structure, the structure has strong water absorption, can quickly absorb exudates of the wound surface, keeps the wound surface dry, prevents infection caused by accumulation of the exudates, and is convenient for management of the exudates.

Description

Technical Field

[0001] This invention relates to the fields of biomedical materials and traditional Chinese medicine, and in particular to a method for preparing a composite hydrogel dressing. Background Technology

[0002] Chronic wounds, such as pressure sores (bedsores) and diabetic foot ulcers, have always been a challenge in clinical nursing due to their complex healing process, long duration, and susceptibility to infection. Traditional Chinese medicine theory considers these wounds to be a case of "deficiency of the root and excess of the branch," with the core pathogenesis being "prolonged bed rest injures Qi, leading to Qi deficiency and blood stasis, resulting in malnourishment of the skin and muscles, further complicated by pathogenic factors, causing necrotic tissue to grow." Therefore, treatment should follow the principles of "strengthening the body's resistance and eliminating pathogenic factors" and "removing necrotic tissue and promoting tissue regeneration," that is, replenishing Qi and blood to treat the root cause, and promoting blood circulation, removing blood stasis, and promoting tissue regeneration to treat the symptoms.

[0003] Hydrogels are considered ideal wound dressing matrices due to their high water content, good biocompatibility, and flexibility. Among them, natural polymers such as gelatin (Gel) and chitosan (CS) are highly favored because of their wide availability, biodegradability, low immunogenicity, and inherent bioactivity. However, purely physically blended hydrogels often have poor mechanical properties, making it difficult to meet clinical requirements for dressing strength and durability.

[0004] Currently, commonly used wound dressings in clinical practice include traditional gauze and various novel functional dressings. However, many dressings have limited functions and are insufficient in actively regulating the wound microenvironment, especially in multi-target synergistic treatment based on traditional Chinese medicine theory. Traditional Chinese medicine external application formulations (such as ointments and powders) have theoretical advantages, but often suffer from poor adhesion, difficulty in filling irregular wound cavities, painful dressing changes, and uncontrollable drug release. Summary of the Invention

[0005] To address the aforementioned shortcomings in the existing technology, this invention provides a method for preparing a composite hydrogel dressing, which aims to solve problems such as poor adhesion, difficulty in filling irregular wound cavities, painful dressing changes, and uncontrollable drug release.

[0006] To achieve the above-mentioned objectives, the technical solution adopted by the present invention is as follows: a method for preparing a composite hydrogel dressing, characterized by comprising the following steps: A1. Raw material preparation: 20-40 parts of Astragalus membranaceus, 10-20 parts of Atractylodes macrocephala, 10-20 parts of Angelica sinensis, 5-15 parts of Carthamus tinctorius, 3-10 parts of Dracaena cochinchinensis, and 5-15 parts of Angelica dahurica. A2. Raw material selection: The weight ratio of the raw materials is as follows: Astragalus membranaceus 30 parts, Atractylodes macrocephala 15 parts, Angelica sinensis 15 parts, Carthamus tinctorius 10 parts, Dragon's blood 5 parts, Angelica dahurica 10 parts; A3. Raw material weighing: The mass-volume percentage (w / v) of each component in the hydrogel dressing in the mixed solution before crosslinking is as follows: Traditional Chinese medicine active extract (RM) 0.5%-2%, gelatin (Gel) 15%-25%, chitosan (CS) 3%-5%; A4. Raw material mixing: The mass-volume percentage (w / v) of each component in the hydrogel dressing in the mixed solution before crosslinking is: 1% active extract of traditional Chinese medicine (RM), 20% gelatin (Gel), and 4% chitosan (CS). The hydrogel prepared under this ratio has the highest tensile strength.

[0007] Further, including step S1. Preparation of active extract (RM) of traditional Chinese medicine: weigh out Astragalus membranaceus, Atractylodes macrocephala, Angelica sinensis, Carthamus tinctorius, Daemonorops draco, and Angelica dahurica according to the prescription, add 8-12 times the amount of water and soak for 0.5-1.5 hours, decoct 1-3 times, 1-2 hours each time, filter, combine the filtrates, concentrate under reduced pressure to a concentrated solution with a relative density of 1.03-1.08 (measured at 60℃), cool for later use or dry at low temperature to form an extract powder; Step S2. Preparation of gelatin-chitosan mixed solution: Add gelatin powder to a 1% (v / v) aqueous acetic acid solution and stir in a water bath at 50-65℃ until completely dissolved to obtain a gelatin solution; add chitosan powder to another 1% (v / v) aqueous acetic acid solution and stir in a water bath at 50-65℃ until completely dissolved to obtain a chitosan solution; Step S3. Preparation of drug-loaded composite hydrogel precursor: Mix the gelatin solution obtained in step S2 with the chitosan solution and stir continuously at 50-65℃; then add the concentrated solution or extract powder of active traditional Chinese medicine obtained in step S1 to the mixed solution and stir until uniformly mixed to obtain a viscous RM-Gel-CS homogeneous mixture. Step S4. Gel formation and crosslinking: Pour the homogeneous mixture obtained in step S3 into a mold and let it stand at room temperature (20-25℃) or in a refrigerator at 4℃ for 6-24 hours to allow it to gel, thus obtaining the nascent RM-Gel-CS composite hydrogel. Step S5. Post-processing: After the cross-linking is completed, the hydrogel is taken out from the trisodium citrate solution and rinsed with purified water or PBS buffer to remove the residual cross-linking agent and acid on the surface. Then, it is freeze-dried or vacuum-dried to obtain the Qi-invigorating, blood-activating, necrotic tissue-regenerating composite hydrogel dressing (RM-Gel-CS-T).

[0008] Furthermore, the hydrogel rinsed in step S5 is placed directly into a sterile package and sterilized by irradiation before being used as a wet dressing.

[0009] Furthermore, the nascent hydrogel described in step S4 is immersed in a 15%-25% trisodium citrate aqueous solution and crosslinked at 4-25°C for 48-96 hours.

[0010] Furthermore, the concentration of the trisodium citrate aqueous solution in step S4 is 20%, and the cross-linking soaking time is 72 hours.

[0011] Furthermore, the hydrogel dressing is applied to the wound in the form of a dry sheet, a porous sponge, or directly as a moist gel.

[0012] The beneficial effects of this invention are as follows: This invention discloses a method for preparing a composite hydrogel dressing, strictly adhering to the principles of traditional Chinese medicine (TCM) formulation. Astragalus membranaceus (Huang Qi), the principal herb, greatly replenishes vital energy, strengthens the exterior, promotes tissue regeneration, and addresses the root cause of "qi deficiency." Atractylodes macrocephala (Bai Zhu), invigorates the spleen, replenishes qi, dries dampness, and promotes diuresis, assisting Astragalus membranaceus in replenishing qi and simultaneously dispelling "dampness" from the wound. Together, they serve as the principal herbs, working synergistically to replenish qi, promote tissue regeneration, strengthen the spleen, and eliminate dampness, laying the foundation for "vital energy" in wound repair. Angelica sinensis (Dang Gui), the assistant herb, replenishes and invigorates blood, resolving blood stasis without harming the body's vital energy. Carthamus tinctorius (Hong Hua), invigorates blood, unblocks meridians, disperses blood stasis, and relieves pain, enhancing the local blood-activating power of Angelica sinensis. Dragon's blood (Xue Jie) specifically targets the blood, invigorating blood, relieving pain, resolving blood stasis, stopping bleeding, and promoting tissue regeneration, specifically promoting the healing of necrotic tissue. Together, these three herbs collectively address the core issue of "blood stasis." Angelica dahurica (Bai Zhi), the adjuvant herb, reduces swelling and drains pus, dries dampness, and promotes wound healing. It also guides the other herbs directly to the affected area, assisting the principal and assistant herbs in dispelling pathogenic factors and necrotic tissue, harmonizing the medicinal properties, and promoting wound healing. The formula is a comprehensive combination that addresses both the symptoms and the root cause, working together to invigorate qi and blood, promote blood circulation and remove blood stasis, promote the elimination of toxins and pus, and promote tissue regeneration. It systematically intervenes in the pathological process of chronic wounds from multiple aspects, which is highly consistent with modern medical healing strategies.

[0013] This invention discloses a method for preparing a composite hydrogel dressing, using natural polymer gelatin and chitosan as matrices. Both have excellent biocompatibility, can be naturally degraded in vivo, and will not have adverse effects on the body. The broad-spectrum antibacterial properties of chitosan provide the dressing with basic anti-infection capabilities, effectively preventing wound infection. Cross-linking through trisodium citrate soaking alters the internal structure of the hydrogel, enhancing intermolecular interactions and effectively improving its mechanical strength, such as tensile strength, making it less prone to breakage during clinical use and thus more practical and durable.

[0014] This invention discloses a method for preparing a composite hydrogel dressing. The preparation process eliminates the need for toxic chemical cross-linking agents, such as glutaraldehyde, thus avoiding the damage to the active ingredients of traditional Chinese medicine and potential harm to the human body caused by toxic chemicals. A gentle immersion cross-linking method is employed, which is simple, controllable, and beneficial for preserving the active ingredients of the traditional Chinese medicine. Simultaneously, by precisely controlling the mass-volume percentage of active extracts of the traditional Chinese medicine in the mixed solution, the drug loading is controllable, ensuring a stable drug content in each prepared dressing and guaranteeing consistent therapeutic effects. The three-dimensional network structure of the hydrogel provides an excellent carrier for the sustained release of the traditional Chinese medicine components, enabling the slow and continuous release of these components onto the wound surface, prolonging the duration of action and improving drug utilization.

[0015] This invention discloses a method for preparing a composite hydrogel dressing. The resulting hydrogel dressing is soft and hydrophilic, capable of closely conforming to wounds of various shapes, whether flat or irregular, providing excellent coverage and a moist healing environment. This moist environment promotes cell proliferation and migration, accelerating wound healing and reducing pain during dressing changes. The dried hydrogel forms a porous, sponge-like structure with strong water absorption, rapidly absorbing wound exudate, keeping the wound dry, preventing exudate buildup and infection, and facilitating exudate management. Attached Figure Description

[0016] Figure 1 This is a process flow diagram of a method for preparing a composite hydrogel dressing according to the present invention; Figure 2 This is a flowchart of a method for preparing a composite hydrogel dressing according to the present invention. Detailed Implementation

[0017] The specific embodiments of the present invention will be further described below with reference to the accompanying drawings. Identical components are indicated by the same reference numerals.

[0018] It should be noted that the terms “front,” “back,” “left,” “right,” “up,” and “down” used in the following description refer to the directions shown in the attached diagram, while the terms “inside” and “outside” refer to the directions toward or away from the geometric center of a specific component, respectively.

[0019] To make the content of this invention easier to understand, the technical solutions in the embodiments of this invention will be clearly and completely described below with reference to the accompanying drawings.

[0020] like Figures 1 to 2 As shown, a method for preparing a composite hydrogel dressing includes the following steps: A1. Raw material preparation: 20-40 parts of Astragalus membranaceus, 10-20 parts of Atractylodes macrocephala, 10-20 parts of Angelica sinensis, 5-15 parts of Carthamus tinctorius, 3-10 parts of Dracaena cochinchinensis, and 5-15 parts of Angelica dahurica. A2. Raw material selection: The weight ratio of the raw materials is as follows: Astragalus membranaceus 30 parts, Atractylodes macrocephala 15 parts, Angelica sinensis 15 parts, Carthamus tinctorius 10 parts, Dragon's blood 5 parts, Angelica dahurica 10 parts; A3. Raw material weighing: The mass-volume percentage (w / v) of each component in the hydrogel dressing in the mixed solution before crosslinking is as follows: Traditional Chinese medicine active extract (RM) 0.5%-2%, gelatin (Gel) 15%-25%, chitosan (CS) 3%-5%; A4. Raw material mixing: The mass-volume percentage (w / v) of each component in the hydrogel dressing in the mixed solution before crosslinking is: 1% active extract of traditional Chinese medicine (RM), 20% gelatin (Gel), and 4% chitosan (CS). The hydrogel prepared under this ratio has the highest tensile strength.

[0021] The preparation of the active extract (RM) of traditional Chinese medicine includes step S1: weigh out Astragalus membranaceus, Atractylodes macrocephala, Angelica sinensis, Carthamus tinctorius, Daemonorops draco, and Angelica dahurica according to the prescription, soak in 8-12 times the amount of water for 0.5-1.5 hours, decoct 1-3 times, 1-2 hours each time, filter, combine the filtrates, concentrate under reduced pressure to a concentrated solution with a relative density of 1.03-1.08 (measured at 60℃), cool for later use or dry at low temperature to form an extract powder; Step S2. Preparation of gelatin-chitosan mixed solution: Add gelatin powder to a 1% (v / v) aqueous acetic acid solution and stir in a water bath at 50-65℃ until completely dissolved to obtain a gelatin solution; add chitosan powder to another 1% (v / v) aqueous acetic acid solution and stir in a water bath at 50-65℃ until completely dissolved to obtain a chitosan solution; Step S3. Preparation of drug-loaded composite hydrogel precursor: Mix the gelatin solution obtained in step S2 with the chitosan solution and stir continuously at 50-65℃; then add the concentrated solution or extract powder of active traditional Chinese medicine obtained in step S1 to the mixed solution and stir until uniformly mixed to obtain a viscous RM-Gel-CS homogeneous mixture. Step S4. Gel formation and crosslinking: Pour the homogeneous mixture obtained in step S3 into a mold and let it stand at room temperature (20-25℃) or in a refrigerator at 4℃ for 6-24 hours to allow it to gel, thus obtaining the nascent RM-Gel-CS composite hydrogel. Step S5. Post-processing: After the cross-linking is completed, the hydrogel is removed from the trisodium citrate solution and rinsed with purified water or PBS buffer to remove the residual cross-linking agent and acid on the surface. Then, it is freeze-dried or vacuum-dried to obtain the Qi-invigorating, blood-activating, necrotic tissue-regenerating composite hydrogel dressing (RM-Gel-CS-T).

[0022] The hydrogel rinsed in step S5 is placed directly into a sterile package and sterilized by irradiation before being used as a wet dressing.

[0023] In step S4, the nascent hydrogel is immersed in a 15%-25% trisodium citrate aqueous solution and crosslinked at 4-25°C for 48-96 hours.

[0024] In step S4, the concentration of the trisodium citrate aqueous solution is 20%, and the cross-linking soaking time is 72 hours.

[0025] Hydrogel dressings are applied to the wound in the form of dry sheets, porous sponges, or directly as moist gels. Embodiment 1 of this invention patent: 1. Raw material preparation and selection 1.1 Weigh out 30 parts of Astragalus membranaceus, 15 parts of Atractylodes macrocephala, 15 parts of Angelica sinensis, 10 parts of Carthamus tinctorius, 5 parts of Draconis blood, and 10 parts of Angelica dahurica.

[0026] 1.2 The mass-volume percentage (w / v) of each component in the hydrogel dressing in the mixed solution before crosslinking was determined as follows: 1% active extract of traditional Chinese medicine (RM), 20% gelatin (Gel), and 4% chitosan (CS).

[0027] 2. Preparation of active extracts (RM) from traditional Chinese medicine 2.1 Mix the weighed Astragalus membranaceus, Atractylodes macrocephala, Angelica sinensis, Carthamus tinctorius, Dragon's Blood, and Angelica dahurica.

[0028] 2.2 Add 10 times the amount of water and soak for 1 hour.

[0029] 2.3 Boil twice, 1.5 hours each time.

[0030] 2.4 Filter and combine the filtrates.

[0031] 2.5 Concentrate under reduced pressure to a concentration of 1.05 (measured at 60℃), then cool and set aside.

[0032] 3. Preparation of gelatin-chitosan mixed solution 3.1 Add gelatin powder to a 1% (v / v) aqueous solution of acetic acid and stir in a 60°C water bath until completely dissolved to obtain a gelatin solution.

[0033] 3.2 Add chitosan powder to another 1% (v / v) aqueous acetic acid solution and stir in a 60°C water bath until completely dissolved to obtain a chitosan solution.

[0034] 4. Preparation of drug-loaded composite hydrogel precursors 4.1 Mix the gelatin solution and chitosan solution and stir continuously at 60°C.

[0035] 4.2 Add the above-prepared concentrated extract of active Chinese herbal medicine to the mixed solution and stir until it is evenly mixed to obtain a viscous RM-Gel-CS homogeneous mixture.

[0036] 5. Gel formation and cross-linking 5.1 Pour the homogenized mixture into the mold.

[0037] 5.2 Let it stand in a refrigerator at 4℃ for 12 hours to allow it to gel, and obtain the nascent RM-Gel-CS composite hydrogel.

[0038] 5.3 The nascent hydrogel was immersed in a 20% trisodium citrate aqueous solution and crosslinked at 10°C for 72 hours.

[0039] 6. Post-processing 6.1 Remove the cross-linked hydrogel from the trisodium citrate solution and rinse with purified water.

[0040] 6.2 The mixture was freeze-dried to obtain a composite hydrogel dressing (RM-Gel-CS-T) that promotes blood circulation, removes necrotic tissue, and promotes tissue regeneration.

[0041] 6.3 The rinsed hydrogel is placed directly into a sterile package and sterilized by irradiation before being used as a wet dressing.

[0042] Embodiment 2 of this invention patent: 1. Raw material preparation and selection 1.1 Weigh out 25 parts of Astragalus membranaceus, 12 parts of Atractylodes macrocephala, 12 parts of Angelica sinensis, 8 parts of Carthamus tinctorius, 4 parts of Dragon's Blood, and 8 parts of Angelica dahurica.

[0043] 1.2 The mass-volume percentage (w / v) of each component in the hydrogel dressing in the mixed solution before crosslinking was determined as follows: RM active extract of traditional Chinese medicine 0.8%, gelatin 18%, and chitosan 3.5%.

[0044] 2. Preparation of active extracts (RM) from traditional Chinese medicine 2.1 Mix the weighed Astragalus membranaceus, Atractylodes macrocephala, Angelica sinensis, Carthamus tinctorius, Dragon's Blood, and Angelica dahurica.

[0045] 2.2 Add 9 times the amount of water and soak for 1.2 hours.

[0046] 2.3 Boil three times, one hour each time.

[0047] 2.4 Filter and combine the filtrates.

[0048] 2.5 Concentrate under reduced pressure to a concentration of 1.04 (measured at 60℃), then cool and set aside.

[0049] 3. Preparation of gelatin-chitosan mixed solution 3.1 Add gelatin powder to a 1% (v / v) aqueous solution of acetic acid and stir in a 55°C water bath until completely dissolved to obtain a gelatin solution.

[0050] 3.2 Add chitosan powder to another 1% (v / v) aqueous acetic acid solution and stir in a 55°C water bath until completely dissolved to obtain a chitosan solution.

[0051] 4. Preparation of drug-loaded composite hydrogel precursors 4.1 Mix the gelatin solution and chitosan solution and stir continuously at 55°C.

[0052] 4.2 Add the above-prepared concentrated extract of active Chinese herbal medicine to the mixed solution and stir until it is evenly mixed to obtain a viscous RM-Gel-CS homogeneous mixture.

[0053] 5. Gel formation and cross-linking 5.1 Pour the homogenized mixture into the mold.

[0054] 5.2 Allow it to stand at room temperature (22℃) for 18 hours to allow it to gel, thus obtaining the nascent RM-Gel-CS composite hydrogel.

[0055] 5.3 The nascent hydrogel was immersed in an 18% trisodium citrate aqueous solution and crosslinked at 15°C for 60 hours.

[0056] 6. Post-processing 6.1 Remove the cross-linked hydrogel from the trisodium citrate solution and rinse with PBS buffer.

[0057] 6.2 Vacuum drying was performed to obtain the Qi-invigorating, blood-activating, necrotic tissue-regenerating composite hydrogel dressing (RM-Gel-CS-T).

[0058] 6.3 The rinsed hydrogel is placed directly into a sterile package and sterilized by irradiation before being used as a wet dressing.

[0059] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing a composite hydrogel dressing, characterized in that, The following steps are included: A1. Raw material preparation: 20-40 parts Astragalus membranaceus, 10-20 parts Atractylodes macrocephala, 10-20 parts Angelica sinensis, 5-15 parts Carthamus tinctorius, 3-10 parts Dragon's Blood, and 5-15 parts Angelica dahurica; A2. Raw material selection: The weight ratio of the raw materials is as follows: Astragalus membranaceus 30 parts, Atractylodes macrocephala 15 parts, Angelica sinensis 15 parts, Carthamus tinctorius 10 parts, Dragon's blood 5 parts, Angelica dahurica 10 parts; A3. Raw material weighing: The mass-volume percentage (w / v) of each component in the hydrogel dressing in the mixed solution before crosslinking is as follows: Traditional Chinese medicine active extract (RM) 0.5%-2%, gelatin (Gel) 15%-25%, chitosan (CS) 3%-5%; A4. Raw material mixing: The mass-volume percentage (w / v) of each component in the hydrogel dressing in the mixed solution before crosslinking is: 1% active extract of traditional Chinese medicine (RM), 20% gelatin (Gel), and 4% chitosan (CS). The hydrogel prepared under this ratio has the highest tensile strength.

2. The method for preparing a composite hydrogel dressing according to claim 1, characterized in that: The preparation of the active extract (RM) of traditional Chinese medicine includes step S1: weigh out Astragalus membranaceus, Atractylodes macrocephala, Angelica sinensis, Carthamus tinctorius, Daemonorops draco, and Angelica dahurica according to the prescription, soak in 8-12 times the amount of water for 0.5-1.5 hours, decoct 1-3 times, 1-2 hours each time, filter, combine the filtrates, concentrate under reduced pressure to a concentrated solution with a relative density of 1.03-1.08 (measured at 60℃), cool for later use or dry at low temperature to form an extract powder; Step S2. Preparation of gelatin-chitosan mixed solution: Add gelatin powder to a 1% (v / v) aqueous acetic acid solution and stir in a water bath at 50-65℃ until completely dissolved to obtain a gelatin solution; add chitosan powder to another 1% (v / v) aqueous acetic acid solution and stir in a water bath at 50-65℃ until completely dissolved to obtain a chitosan solution; Step S3. Preparation of drug-loaded composite hydrogel precursor: Mix the gelatin solution obtained in step S2 with the chitosan solution and stir continuously at 50-65℃; Subsequently, the concentrated solution or extract powder of active traditional Chinese medicine obtained in step S1 is added to the mixed solution and stirred until it is evenly mixed to obtain a viscous RM-Gel-CS homogeneous mixture. Step S4. Gel formation and crosslinking: Pour the homogeneous mixture obtained in step S3 into a mold and let it stand at room temperature (20-25℃) or in a refrigerator at 4℃ for 6-24 hours to allow it to gel, thus obtaining the nascent RM-Gel-CS composite hydrogel. Step S5. Post-processing: After the cross-linking is completed, the hydrogel is taken out from the trisodium citrate solution and rinsed with purified water or PBS buffer to remove the residual cross-linking agent and acid on the surface. Then, it is freeze-dried or vacuum-dried to obtain the Qi-invigorating, blood-activating, necrotic tissue-regenerating composite hydrogel dressing (RM-Gel-CS-T).

3. The method for preparing a composite hydrogel dressing according to claim 2, characterized in that: The hydrogel rinsed in step S5 is placed directly into a sterile package and sterilized by irradiation before being used as a wet dressing.

4. The method for preparing a composite hydrogel dressing according to claim 2, characterized in that: The nascent hydrogel described in step S4 is immersed in a 15%-25% trisodium citrate aqueous solution and crosslinked at 4-25°C for 48-96 hours.

5. The method for preparing a composite hydrogel dressing according to claim 2, characterized in that: The concentration of the trisodium citrate aqueous solution in step S4 is 20%, and the cross-linking soaking time is 72 hours.

6. The method for preparing a composite hydrogel dressing according to claim 1, characterized in that: The hydrogel dressing is applied to the wound in the form of a dry sheet, a porous sponge, or directly as a moist gel.

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