Radiotherapy injury repair injection hydrogel and preparation method thereof
By preparing a radiotherapy damage repair injectable hydrogel, an anti-inflammatory traditional Chinese medicine formula is encapsulated in PLGA microspheres and cross-linked with gelatin and sodium oxidized alginate to form an injectable hydrogel. This solves the treatment problem of radiotherapy damage to deep organs and achieves local slow release and efficient repair of the anti-inflammatory traditional Chinese medicine formula.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- HEBEI PROVINCE CANGZHOU HOSPITAL OF INTEGRATED TRADITIONAL & WESTERN MEDICINE
- Filing Date
- 2026-01-27
- Publication Date
- 2026-04-17
AI Technical Summary
Existing Chinese herbal compound components cannot effectively treat radiation damage to deep organs such as the abdominal cavity and pelvic cavity through topical application, especially complications such as radiation proctitis, radiation cystitis, and inflammation, ulceration, and fibrosis of the cervix and vaginal mucosa caused by radiotherapy.
An injectable hydrogel for radiotherapy damage repair was prepared by encapsulating an anti-inflammatory traditional Chinese medicine formula in PLGA microspheres and mixing it with gelatin and sodium alginate solution to form an injectable hydrogel, thereby achieving localized slow release of the anti-inflammatory traditional Chinese medicine formula. Controlled sustained release was achieved by utilizing the cross-linking reaction between gelatin and sodium alginate.
This method achieves highly effective local treatment of radiotherapy-induced damage to deep organs using anti-inflammatory traditional Chinese medicine formulas, alleviating inflammatory responses, promoting tissue repair, and avoiding the limitations of topical application. It is suitable for treating radiotherapy-induced damage to deep organs such as the abdominal cavity and pelvis.
Smart Images
Figure CN121868432A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of biomedical materials technology, and in particular to an injectable hydrogel for repairing radiotherapy damage and its preparation method. Background Technology
[0002] Radiation therapy is one of the main treatment methods for malignant tumors. However, while killing cancer cells, radiation therapy can cause varying degrees of damage to the normal tissues surrounding the lesion, known as radiation damage. This damage mainly manifests as local inflammation, tissue fibrosis, ulceration, and even necrosis, severely affecting the patient's quality of life and potentially forcing the interruption of radiotherapy, thus impacting the effectiveness of tumor treatment.
[0003] Currently, clinical methods for preventing and treating radiation-induced injuries are limited. Among these, Traditional Chinese Medicine (TCM), guided by the theories of "clearing heat and detoxifying, promoting blood circulation and removing blood stasis, and promoting tissue regeneration and wound healing," shows unique advantages in alleviating the side effects of radiotherapy. Numerous studies and clinical practices have demonstrated that certain TCM compound components possess significant anti-inflammatory, antioxidant, angiogenesis-promoting, and tissue regeneration-enhancing effects.
[0004] However, existing traditional Chinese medicine compound preparations are usually formulated into ointments, creams, or lotions, which can only be applied topically. This method of administration is effective for radiation dermatitis located on the skin surface. However, for malignant tumors in the abdominal and pelvic cavities (such as cervical cancer, colorectal cancer, and bladder cancer), radiotherapy often leads to complications such as radiation proctitis, radiation cystitis, and inflammation, ulceration, fibrosis, and stenosis of the cervical and vaginal mucosa. The existing topical application methods are not suitable for treating radiation damage to deep organs such as the abdominal and pelvic cavities. Summary of the Invention
[0005] To address the problem that existing methods of administering traditional Chinese medicine compound components are not suitable for treating radiotherapy injuries to deep organs such as the abdominal cavity and pelvis, this invention provides a method for preparing a radiotherapy injury repair injection hydrogel. This method enables the local injection of anti-inflammatory traditional Chinese medicine formulations at the radiotherapy injury site, thus solving the problem that existing methods of administering traditional Chinese medicine compound components are not suitable for treating radiotherapy injuries to deep organs such as the abdominal cavity and pelvis.
[0006] The technical solution adopted by this invention to solve its technical problem is: A method for preparing a radiotherapy damage repair injectable hydrogel includes the following steps: S1: PLGA-encapsulated anti-inflammatory traditional Chinese medicine microspheres were prepared using anti-inflammatory traditional Chinese medicine formulations, polylactic acid-glycolic acid copolymers, and polyvinyl alcohol as raw materials. S2: Disperse the PLGA-encapsulated anti-inflammatory traditional Chinese medicine microspheres in a gelatin solution to obtain solution A; S3: Mix the solution A with sodium alginate oxidase solution to obtain a radiotherapy damage repair injection hydrogel.
[0007] Optionally, PLGA-encapsulated anti-inflammatory traditional Chinese medicine microspheres are prepared using anti-inflammatory traditional Chinese medicine formulations, polylactic acid-glycolic acid copolymers, and polyvinyl alcohol as raw materials, including: S11: The anti-inflammatory traditional Chinese medicine formula is mixed with the polylactic acid-glycolic acid copolymer and then dissolved in dichloromethane to obtain a mixed solution; S12: The mixed solution is added to a polyvinyl alcohol solution, and after stirring, centrifugation, and freeze-drying, PLGA-encapsulated anti-inflammatory traditional Chinese medicine microspheres are obtained.
[0008] Optionally, the mass ratio of the anti-inflammatory traditional Chinese medicine formulation to the polylactic acid-glycolic acid copolymer is 1:(8-12).
[0009] Optionally, the mass concentration of polyvinyl alcohol in the polyvinyl alcohol solution is (0.5-1.5)%.
[0010] Optionally, the polylactic acid-glycolic acid copolymer has a molecular weight of 10,000.
[0011] Optionally, the anti-inflammatory traditional Chinese medicine formula is the Lithospermum erythrorhizon and Jinhuang Ruyi formula.
[0012] Optionally, the Zicao Jinhuang Ruyi formula, by weight, comprises the following components: 20-40 parts of Zicao (Lithospermum erythrorhizon); 5-15 parts of Angelica sinensis; 5-10 parts of Trichosanthes kirilowii; 10-20 parts of Angelica dahurica; 10-30 parts of Citrus reticulata peel; 10-20 parts of Magnolia officinalis; 10-20 parts of Atractylodes lancea (stir-fried with wheat bran); 10-20 parts of Phellodendron chinense (processed with salt); 10-30 parts of Curcuma longa; 5-8 parts of Pheretima aspergillum; 10-15 parts of Rheum palmatum; and 5-15 parts of Glycyrrhiza uralensis.
[0013] Optionally, the oxidized sodium alginate is obtained by reacting sodium alginate and sodium periodate as raw materials at room temperature and in the dark.
[0014] Optionally, the molar ratio of sodium alginate to sodium periodate is 2:1.
[0015] Another object of the present invention is to provide a radiotherapy damage repair injection hydrogel, which is prepared by the radiotherapy damage repair injection hydrogel preparation method described above.
[0016] The beneficial effects of this invention are: The present invention provides a method for preparing a radiotherapy damage repair injectable hydrogel, in which an anti-inflammatory traditional Chinese medicine formula is embedded in PLGA microspheres, the microspheres are then dispersed in a gelatin solution and mixed with an oxidized sodium alginate solution, and the cross-linking of gelatin and oxidized sodium alginate forms an injectable hydrogel, thereby achieving local slow release of the anti-inflammatory traditional Chinese medicine formula and achieving the purpose of efficient repair of radiotherapy damage. Attached Figure Description
[0017] The present invention will be further described below with reference to the accompanying drawings and embodiments.
[0018] Figure 1 This is a comparison diagram showing how the combination of Lithospermum erythrorhizon and Jinhuang Ruyi in this invention promotes vascular endothelial proliferation. Figure 2 This is a scanning electron microscope image of the blank PLGA microspheres in Embodiment 1 of the present invention; Figure 3 This is a scanning electron microscope image of the PLGA-encapsulated anti-inflammatory traditional Chinese medicine microspheres in Example 1 of this invention; Figure 4 This is a photograph of the radiotherapy damage repair injection hydrogel prepared in Example 1 of the present invention. Detailed Implementation
[0019] The present invention will now be described in further detail. The embodiments described below are exemplary and intended to explain the present invention, and should not be construed as limiting the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.
[0020] To address the problem that existing methods of administering traditional Chinese medicine compound components are unsuitable for treating radiotherapy injuries to deep organs such as the abdominal cavity and pelvis, this invention provides a method for preparing a radiotherapy injury repair injection hydrogel, which includes the following steps: S1: PLGA-encapsulated anti-inflammatory traditional Chinese medicine microspheres were prepared using anti-inflammatory traditional Chinese medicine formulations, polylactic acid-glycolic acid copolymers, and polyvinyl alcohol as raw materials. The anti-inflammatory traditional Chinese medicine formulation can be selected as needed; polylactic acid-glycolic acid copolymer (PLGA) is a biodegradable polymer material with good biocompatibility and degradability. This invention introduces the required anti-inflammatory traditional Chinese medicine formulation by encapsulating anti-inflammatory traditional Chinese medicine formulation microspheres with PLGA, which helps to improve the stability of the anti-inflammatory traditional Chinese medicine formulation. It can achieve local injection treatment at the site of deep organ radiotherapy damage while realizing the slow release of the anti-inflammatory traditional Chinese medicine formulation to promote the healing of damaged tissues.
[0021] S2: Disperse PLGA-encapsulated anti-inflammatory traditional Chinese medicine microspheres in a gelatin solution to obtain solution A; The preferred mass concentration of the gelatin solution is 15-25%, and more preferably 20%; the gelatin solution is prepared by dissolving gelatin in PBS at 37 °C for 0.5 h. The preferred mass ratio of PLGA-encapsulated anti-inflammatory traditional Chinese medicine microspheres to gelatin solution is 1:10.
[0022] S3: Mix solution A with sodium alginate oxidase solution to obtain a radiotherapy damage repair injection hydrogel; The preferred sodium alginate solution is an aqueous solution of sodium alginate, wherein the mass concentration of sodium alginate is 10-20%, and more preferably 15%; preferably, both the gelatin solution and the sodium alginate solution in this invention are filtered and sterilized by a bacterial filter; preferably, the mass ratio of the gelatin solution to the sodium alginate solution is (8~1):(1~8).
[0023] The sodium alginate oxidized molecular chain contains aldehyde groups, which can undergo a Schiff base reaction with the amino groups on the gelatin molecular chain to achieve rapid cross-linking and gelation, thereby improving the stability and utilization rate of the anti-inflammatory traditional Chinese medicine formula. Utilizing the injectability of sodium alginate oxidized hydrogel, local injection treatment of the anti-inflammatory traditional Chinese medicine formula at the radiotherapy injury site can be achieved. By controlling the pH value change at the injury site, the anti-inflammatory traditional Chinese medicine formula can be released in a controlled manner, which can be used for the treatment of radiotherapy injuries to abdominal and pelvic malignant tumors.
[0024] The method for preparing radiotherapy damage repair injectable hydrogel provided by this invention involves embedding an anti-inflammatory traditional Chinese medicine formula in PLGA microspheres, dispersing the microspheres in a solution containing amino groups such as gelatin, and then mixing them with a sodium alginate oxidase solution. The amino groups of gelatin react with the sodium alginate oxidase to form an injectable hydrogel with dynamic cross-linking of imine bonds, thereby achieving local slow release of the anti-inflammatory traditional Chinese medicine formula and achieving the purpose of efficient repair of radiotherapy damage.
[0025] Specifically, the present invention preferably uses anti-inflammatory traditional Chinese medicine formulas, polylactic acid-glycolic acid copolymers, and polyvinyl alcohol as raw materials to prepare PLGA-encapsulated anti-inflammatory traditional Chinese medicine formula microspheres, comprising: S11: The anti-inflammatory traditional Chinese medicine formula is mixed with polylactic acid-glycolic acid copolymer and then dissolved in dichloromethane to obtain a mixed solution; S12: Add the mixed solution to the polyvinyl alcohol solution, stir, centrifuge, and freeze dry to obtain PLGA-encapsulated anti-inflammatory traditional Chinese medicine microspheres.
[0026] Preferably, the above steps are performed according to the following process: S11: Dissolve the anti-inflammatory traditional Chinese medicine formula and PLGA in dichloromethane according to the formula amount to obtain a mixed solution; S12: Slowly add PVA solution to the mixed solution, stir at 500 r / min for 12 hours using a mechanical stirrer, centrifuge at 3300 r for 10 min, remove the supernatant, add deionized water; repeat three times, then place the remaining suspension in a container; freeze dry at -55℃ for 24 h using a freeze dryer to obtain PLGA-encapsulated anti-inflammatory traditional Chinese medicine microspheres.
[0027] The present invention preferably uses an anti-inflammatory traditional Chinese medicine formulation to polylactic acid-glycolic acid copolymer in a mass ratio of 1:(8-12), and more preferably 1:10, so as to ensure that the anti-inflammatory traditional Chinese medicine formulation is effectively embedded inside the PLGA microspheres while ensuring that the microspheres have good morphology and stability.
[0028] The present invention preferably uses a polyvinyl alcohol concentration of (0.5-1.5)% in the polyvinyl alcohol solution, and more preferably 1%; the polyvinyl alcohol solution in this concentration range can provide suitable interfacial tension, which helps to form a stable emulsion system, thereby preparing PLGA microspheres with uniform particle size; the preferred ratio of anti-inflammatory traditional Chinese medicine formulation, polylactic acid-glycolic acid copolymer and polyvinyl alcohol solution is 1 mg: (8-15) mg: 5 mL.
[0029] The present invention preferably uses a polylactic acid-glycolic acid copolymer with a molecular weight of 10,000. More preferably, the polylactic acid-glycolic acid copolymer is PLGA (50:50, 10K) so that PLGA has a suitable degradation rate and mechanical properties. As a microsphere carrier, it can better control the release rate of anti-inflammatory traditional Chinese medicine formulation, while ensuring the stability of microspheres during preparation and storage.
[0030] The preferred anti-inflammatory traditional Chinese medicine formula of this invention is the Lithospermum erythrorhizon and Jinhuang Ruyi formula. Specifically, the preferred formula, by weight, includes the following components: Lithospermum erythrorhizon 20-40 parts; Angelica sinensis 5-15 parts; Trichosanthes kirilowii 5-10 parts; Angelica dahurica 10-20 parts; Citrus reticulata peel 10-30 parts; Magnolia officinalis 10-20 parts; Atractylodes lancea stir-fried with wheat bran 10-20 parts; Phellodendron chinense bark stir-fried with salt 10-20 parts; Curcuma longa 10-30 parts; Pheretima aspergillum 5-8 parts; Rheum palmatum 10-15 parts; Glycyrrhiza uralensis 5-15 parts.
[0031] This traditional Chinese medicine formula is for the syndrome of blood stasis obstructing the muscles and skin.
[0032] Explanation: This formula is mainly used to treat radiation-induced skin injuries caused by blood stasis, which obstructs the skin and muscles, resulting in local redness, swelling, and ulceration. Treatment should focus on clearing heat and detoxifying, dispersing blood stasis, and reducing swelling.
[0033] The formula uses Lithospermum erythrorhizon as the principal herb, which cools the blood, invigorates blood circulation, clears heat, and detoxifies. Angelica sinensis, Trichosanthes kirilowii, Angelica dahurica, Citrus reticulata peel, Magnolia officinalis, stir-fried Atractylodes lancea, salt-processed Phellodendron chinense, and Curcuma longa are the assistant herbs. Earthworm and Rheum palmatum are the adjuvant herbs, and Glycyrrhiza uralensis is the guiding herb. Rheum palmatum and Phellodendron chinense clear heat and detoxify, dispel blood stasis and dry dampness, thus eliminating stagnant heat and congealed blood. Curcuma longa and Angelica sinensis break up blood stasis, promote menstruation, and relieve pain; when used with Trichosanthes kirilowii, they can remove blood stasis, reduce swelling, and relieve pain. Magnolia officinalis, Citrus reticulata peel, Atractylodes lancea, and Angelica dahurica regulate qi, dry dampness, disperse nodules, reduce swelling, and relieve pain. Glycyrrhiza uralensis detoxifies and harmonizes the other herbs. The combined effects of these herbs clear heat and detoxify, disperse blood stasis, and reduce swelling. Once the heat toxin is resolved, the blood stasis is dispersed, and the dampness toxin is eliminated, the redness, swelling, heat, and pain naturally subside.
[0034] This traditional Chinese medicine formula has the effects of clearing heat and detoxifying, reducing swelling and relieving pain, and promoting tissue regeneration. It has significant preventive and therapeutic effects on radiation-induced skin and mucous membrane damage. Through compound formulation, it can reduce inflammatory response and promote tissue repair through multiple targets and pathways without producing side effects.
[0035] Furthermore, the preferred formulation of this invention, which contains the following components by weight: 30 parts of Lithospermum erythrorhizon; 10 parts of Angelica sinensis; 6 parts of Trichosanthes kirilowii; 16 parts of Angelica dahurica; 20 parts of Citrus reticulata peel; 15 parts of Magnolia officinalis; 15 parts of Atractylodes lancea stir-fried with wheat bran; 15 parts of Phellodendron chinense bark with salt; 20 parts of Curcuma longa; 6 parts of Pheretima aspergillum; 12 parts of Rheum palmatum; and 10 parts of Glycyrrhiza uralensis.
[0036] This traditional Chinese medicine formula is suitable for external use.
[0037] This formula containing purple gromwell and golden ruyi (a type of medicinal herb) has good anti-inflammatory properties and promotes vascular endothelial cell proliferation. See [link to other formulas]. Figure 1 As shown, 0 (control group) represents the proliferation of vascular endothelial cells when using blank PLGA microspheres in Example 1, and 1 represents the proliferation of vascular endothelial cells when using PLGA-encapsulated anti-inflammatory traditional Chinese medicine microspheres in Example 1.
[0038] This invention preferably uses sodium alginate and sodium periodate as raw materials, reacting them at room temperature and in the dark. Sodium periodate can selectively oxidize the vicinal diol hydroxyl groups on the sodium alginate molecular chain to generate aldehyde groups, thereby obtaining sodium alginate with cross-linking activity. Specifically, this step can be carried out as follows: dissolve sodium alginate in deionized water, add potassium periodate aqueous solution, stir at room temperature and in the dark, preferably stirring for 18 hours; use ethylene glycol to stir and extract unreacted sodium periodate, dialyze using a MWCO 14000 dialysis device for 3 days, and then freeze-dry at -50~-80℃ for 24 hours to form sodium alginate oxide.
[0039] The present invention preferably uses a molar ratio of sodium alginate to sodium periodate of 2:1. This molar ratio ensures that an appropriate amount of hydroxyl groups on the sodium alginate molecular chain are oxidized to aldehyde groups, thereby ensuring the performance of subsequent cross-linking with gelatin to form a hydrogel.
[0040] In summary, this invention discloses a method for preparing an injectable sodium alginate hydrogel of a sustained-release microsphere system of a compound polylactic acid and its copolymer (PLGA) containing a comfrey golden ruyi formula (hereinafter referred to as comfrey formula). The method uses a sodium alginate solution as a base, with some of the sodium alginate containing PLGA microspheres loaded with the comfrey formula. By forming a Schiff base with gelatin, the stability and utilization rate of the comfrey formula are improved. Utilizing the injectability of the sodium alginate hydrogel, local injectable treatment of radiotherapy-damaged sites using the comfrey formula is achieved. Controllable sustained release of comfrey is achieved through pH changes at the damaged site, making it suitable for the treatment of radiotherapy-damaged sites in abdominal and cervical cancer.
[0041] Another object of the present invention is to provide a radiotherapy damage repair injection hydrogel, which is prepared by the radiotherapy damage repair injection hydrogel preparation method described above.
[0042] The radiotherapy damage repair injectable hydrogel provided by this invention encapsulates an anti-inflammatory traditional Chinese medicine formula in PLGA microspheres. The microspheres are then dispersed in a gelatin solution and mixed with an oxidized sodium alginate solution. The cross-linking of gelatin and oxidized sodium alginate forms an injectable hydrogel, thereby achieving localized and slow release of the anti-inflammatory traditional Chinese medicine formula and achieving the goal of efficiently repairing radiotherapy damage.
[0043] The radiotherapy damage repair injectable hydrogel provided by this invention has a three-dimensional network structure that can encapsulate PLGA and anti-inflammatory traditional Chinese medicine microspheres, forming a stable local drug delivery system after injection. The PLGA microspheres slowly degrade within the hydrogel, continuously releasing the anti-inflammatory traditional Chinese medicine formula, thus exerting a long-lasting anti-inflammatory and tissue repair effect. Simultaneously, the hydrogel itself has good biocompatibility and biodegradability, allowing it to be gradually absorbed by the human body without producing toxic side effects.
[0044] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings.
[0045] Example 1 This embodiment provides a method for preparing a radiotherapy damage repair injectable hydrogel, comprising the following steps: S1: Preparation of PLGA-encapsulated anti-inflammatory traditional Chinese medicine microspheres: S11: Dissolve 30mg of the Lithospermum erythrorhizon and 300mg of PLGA (50:50, 10K) in 5mL of dichloromethane to obtain a mixed solution; According to the weight proportions, the Zicao Jinhuang Ruyi formula includes 30 parts of Zicao (Gromwell); 10 parts of Danggui (Angelica sinensis); 6 parts of Tianhuafen (Trichosanthes kirilowii); 16 parts of Baizhi (Angelica dahurica); 20 parts of Chenpi (Citrus reticulata peel); 15 parts of Houpo (Magnolia officinalis); 15 parts of Cangzhu (Atractylodes lancea) stir-fried with wheat bran; 15 parts of Huangbai (Phellodendron chinense) with salt; 20 parts of Jianghuang (Curcuma longa); 6 parts of Dilong (Pheretima aspergillum); 12 parts of Dahuang (Rheum palmatum); and 10 parts of Gancao (Glycyrrhiza uralensis). S12: Slowly add the above mixed solution to 150 mL of PVA solution (1 wt%), stir at 500 r / min for 12 hours using a mechanical stirrer, centrifuge at 3300 r for 10 min, remove the supernatant, add deionized water; repeat three times, then place the remaining suspension in a container; freeze dry at -55℃ for 24 h using a freeze dryer to obtain PLGA-encapsulated anti-inflammatory traditional Chinese medicine microspheres; S2: Dissolve gelatin in PBS at 37 ℃ for 0.5 h to prepare a gelatin solution with a mass concentration of 20%; encapsulate 5 mg PLGA with anti-inflammatory traditional Chinese medicine microspheres and disperse them in 50 mg gelatin solution by ultrasonication, then filter and sterilize to obtain solution A.
[0046] S3: Dissolve 80 mmol of sodium alginate in 320 mL of deionized water to obtain a sodium alginate solution; dissolve 40 mmol of NaIO4 in 80 mL of deionized water to obtain a NaIO4 solution; add the NaIO4 solution to the sodium alginate solution and stir in the dark at room temperature for 18 h; use 20 mL of ethylene glycol to stir and extract unreacted sodium periodate, dialyze at MWCO 14000 for 3 days, and then freeze-dry at -75℃ for 24 h to form oxidized sodium alginate; dissolve the oxidized sodium alginate in deionized water, filter it through a bacterial filter to sterilize it, and prepare a 15% (w / w) oxidized sodium alginate solution; mix solution A and the oxidized sodium alginate solution at a mass ratio of 1:1 and stir rapidly until homogeneous to obtain the radiotherapy damage repair injection hydrogel.
[0047] The scanning electron microscope image of the blank PLGA microspheres in this embodiment is shown below. Figure 2 As shown, the scanning electron microscope image of PLGA-encapsulated anti-inflammatory traditional Chinese medicine microspheres is shown below. Figure 3 As shown in the image, a photograph of the radiotherapy damage repair injection hydrogel prepared in this embodiment is available. Figure 4 As shown.
[0048] Example 2 This embodiment provides a method for preparing a radiotherapy damage repair injectable hydrogel, comprising the following steps: S1: Preparation of PLGA-encapsulated anti-inflammatory traditional Chinese medicine microspheres: S11: Dissolve 30mg of the Lithospermum erythrorhizon and 240mg of PLGA (50:50, 10K) in 4mL of dichloromethane to obtain a mixed solution; According to the weight proportions, the Zicao Jinhuang Ruyi formula includes 20 parts of Zicao (Gromwell); 5 parts of Danggui (Angelica sinensis); 5 parts of Tianhuafen (Trichosanthes kirilowii); 10 parts of Baizhi (Angelica dahurica); 10 parts of Chenpi (Citrus reticulata peel); 10 parts of Houpo (Magnolia officinalis); 10 parts of Cangzhu (Atractylodes lancea) stir-fried with wheat bran; 10 parts of Huangbai (Phellodendron chinense) with salt; 10 parts of Jianghuang (Curcuma longa); 5 parts of Dilong (Pheretima aspergillum); 10 parts of Dahuang (Rheum palmatum); and 5 parts of Gancao (Glycyrrhiza uralensis). S12: Slowly add the above mixed solution to 150 mL of PVA solution (0.5 wt%), stir at 500 r / min for 12 hours using a mechanical stirrer, centrifuge at 3300 r for 10 min, remove the supernatant, add deionized water; repeat three times, and place the remaining suspension in a container; freeze dry at -55℃ for 24 h using a freeze dryer to obtain PLGA-encapsulated anti-inflammatory traditional Chinese medicine microspheres; S2: Dissolve gelatin in PBS at 37 ℃ for 0.5 h to prepare a gelatin solution with a mass concentration of 15%; disperse 5 mg PLGA-encapsulated anti-inflammatory traditional Chinese medicine microspheres in 50 mg gelatin solution by ultrasonication, and filter the solution through a bacterial filter to obtain solution A.
[0049] S3: Dissolve 80 mmol of sodium alginate in 320 mL of deionized water to obtain a sodium alginate solution; dissolve 40 mmol of NaIO4 in 80 mL of deionized water to obtain a NaIO4 solution; add the NaIO4 solution to the sodium alginate solution and stir in the dark at room temperature for 18 h; use 20 mL of ethylene glycol to stir and extract unreacted sodium periodate, dialyze at MWCO 14000 for 3 days, and then freeze-dry at -75℃ for 24 h to form oxidized sodium alginate; dissolve the oxidized sodium alginate in deionized water, filter it through a bacterial filter to sterilize it, and prepare a 15% (w / w) oxidized sodium alginate solution; mix solution A and the oxidized sodium alginate solution at a mass ratio of 1:1 and stir rapidly until homogeneous to obtain the radiotherapy damage repair injection hydrogel.
[0050] Example 3 This embodiment provides a method for preparing a radiotherapy damage repair injectable hydrogel, comprising the following steps: S1: Preparation of PLGA-encapsulated anti-inflammatory traditional Chinese medicine microspheres: S11: Dissolve 30mg of the Lithospermum erythrorhizon and 360mg of PLGA (50:50, 10K) in 6mL of dichloromethane to obtain a mixed solution; According to the weight proportions, the Zicao Jinhuang Ruyi formula includes 40 parts of Zicao (Gromwell); 15 parts of Danggui (Angelica sinensis); 10 parts of Tianhuafen (Trichosanthes kirilowii); 20 parts of Baizhi (Angelica dahurica); 30 parts of Chenpi (Citrus reticulata peel); 20 parts of Houpo (Magnolia officinalis); 20 parts of Cangzhu (Atractylodes lancea) stir-fried with wheat bran; 20 parts of Huangbai (Phellodendron chinense) with salt; 30 parts of Jianghuang (Curcuma longa); 8 parts of Dilong (Pheretima aspergillum); 15 parts of Dahuang (Rheum palmatum); and 15 parts of Gancao (Glycyrrhiza uralensis). S12: Slowly add the above mixed solution to 150 mL of PVA solution (1.5 wt%), stir at 500 r / min for 12 hours using a mechanical stirrer, centrifuge at 3300 r for 10 min, remove the supernatant, add deionized water; repeat three times, and place the remaining suspension in a container; freeze dry at -55℃ for 24 h using a freeze dryer to obtain PLGA-encapsulated anti-inflammatory traditional Chinese medicine microspheres; S2: Dissolve gelatin in PBS at 37 ℃ for 0.5 h to prepare a gelatin solution with a mass concentration of 25%; disperse 5 mg PLGA-encapsulated anti-inflammatory traditional Chinese medicine microspheres in 50 mg gelatin solution by ultrasonication, and filter the solution through a bacterial filter to obtain solution A.
[0051] S3: Dissolve 80 mmol of sodium alginate in 320 mL of deionized water to obtain a sodium alginate solution; dissolve 40 mmol of NaIO4 in 80 mL of deionized water to obtain a NaIO4 solution; add the NaIO4 solution to the sodium alginate solution and stir in the dark at room temperature for 18 h; use 20 mL of ethylene glycol to stir and extract unreacted sodium periodate, dialyze at MWCO 14000 for 3 days, and then freeze-dry at -75℃ for 24 h to form oxidized sodium alginate; dissolve the oxidized sodium alginate in deionized water, filter it through a bacterial filter to sterilize it, and prepare a 15% (w / w) oxidized sodium alginate solution; mix solution A and the oxidized sodium alginate solution at a mass ratio of 1:1 and stir rapidly until homogeneous to obtain the radiotherapy damage repair injection hydrogel.
[0052] Based on the above-described preferred embodiments of the present invention, and through the foregoing description, those skilled in the art can make various changes and modifications without departing from the inventive concept. The technical scope of this invention is not limited to the contents of the specification, but must be determined according to the scope of the claims.
Claims
1. A method for preparing an injectable hydrogel for repairing radiotherapy damage, characterized in that, Includes the following steps: S1: PLGA-encapsulated anti-inflammatory traditional Chinese medicine microspheres were prepared using anti-inflammatory traditional Chinese medicine formulations, polylactic acid-glycolic acid copolymers, and polyvinyl alcohol as raw materials. S2: Disperse the PLGA-encapsulated anti-inflammatory traditional Chinese medicine microspheres in a gelatin solution to obtain solution A; S3: Mix the solution A with sodium alginate oxidase solution to obtain a radiotherapy damage repair injection hydrogel.
2. The preparation method of the radiotherapy damage repair injectable hydrogel as described in claim 1, characterized in that, PLGA-encapsulated anti-inflammatory traditional Chinese medicine microspheres were prepared using anti-inflammatory traditional Chinese medicine formulations, polylactic acid-glycolic acid copolymers, and polyvinyl alcohol as raw materials, including: S11: The anti-inflammatory traditional Chinese medicine formula is mixed with the polylactic acid-glycolic acid copolymer and then dissolved in dichloromethane to obtain a mixed solution; S12: The mixed solution is added to a polyvinyl alcohol solution, and after stirring, centrifugation, and freeze-drying, PLGA-encapsulated anti-inflammatory traditional Chinese medicine microspheres are obtained.
3. The preparation method of the radiotherapy damage repair injectable hydrogel as described in claim 2, characterized in that, The mass ratio of the anti-inflammatory traditional Chinese medicine formulation to the polylactic acid-glycolic acid copolymer is 1:(8-12).
4. The preparation method of the radiotherapy damage repair injection hydrogel as described in claim 2, characterized in that, The mass concentration of polyvinyl alcohol in the polyvinyl alcohol solution is (0.5-1.5)%.
5. The preparation method of the radiotherapy damage repair injectable hydrogel as described in claim 2, characterized in that, The polylactic acid-hydroxyacetic acid copolymer has a molecular weight of 10,000.
6. The method for preparing the radiotherapy damage repair injectable hydrogel as described in claim 2, characterized in that, The anti-inflammatory traditional Chinese medicine formula is the Purple Grass and Golden Ruyi Formula.
7. The method for preparing the radiotherapy damage repair injectable hydrogel as described in claim 6, characterized in that, According to the weight proportions, the Zicao Jinhuang Ruyi formula includes the following components: Zicao 20-40 parts; Danggui 5-15 parts; Tianhuafen 5-10 parts; Baizhi 10-20 parts; Chenpi 10-30 parts; Houpo 10-20 parts; Liangzhu (stir-fried) Cangzhu 10-20 parts; Yanhuangbai 10-20 parts; Jianghuang 10-30 parts; Dilong 5-8 parts; Dahuang 10-15 parts; Gancao Pian 5-15 parts.
8. The method for preparing the radiotherapy damage repair injectable hydrogel according to any one of claims 1-7, characterized in that, The oxidized sodium alginate is obtained by reacting sodium alginate and sodium periodate at room temperature in the dark.
9. The method for preparing the radiotherapy damage repair injectable hydrogel as described in claim 8, characterized in that, The molar ratio of sodium alginate to sodium periodate is 2:
1.
10. A radiotherapy damage repair injectable hydrogel, characterized in that, The hydrogel for radiotherapy damage repair injection is prepared using the method described in any one of claims 1-9.