CN120815035A - A thermosensitive gel composition for auxiliary treatment of radiation proctitis and its preparation method - Google Patents
A thermosensitive gel composition for auxiliary treatment of radiation proctitis and its preparation methodInfo
- Publication number
- CN120815035A CN120815035A CN202511335505.8A CN202511335505A CN120815035A CN 120815035 A CN120815035 A CN 120815035A CN 202511335505 A CN202511335505 A CN 202511335505A CN 120815035 A CN120815035 A CN 120815035A
- Authority
- CN
- China
- Prior art keywords
- parts
- solution
- curcumin
- sodium alginate
- gel composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/542—Carboxylic acids, e.g. a fatty acid or an amino acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/61—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5089—Processes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
本发明涉及温敏凝胶技术领域，具体涉及一种辅助治疗放射性直肠炎的温敏凝胶组合物及其制备方法。所述温敏凝胶组合物的制备原料，包括以下重量份的组分：姜黄素@海藻酸钠1.6‑3.2份、CS‑PCA‑Arg 2‑4份、泊洛沙姆407 45‑90份、卡波姆940 3‑6份、透明质酸钠6‑12份；制得的温敏凝胶组合物具有较好的稳定性，可用于辅助治疗放射性直肠炎。
The present invention relates to the technical field of thermosensitive gels, and more particularly to a thermosensitive gel composition for the adjunctive treatment of radiation proctitis and a preparation method thereof. The thermosensitive gel composition is prepared from raw materials comprising the following components by weight: 1.6-3.2 parts of curcumin@sodium alginate, 2-4 parts of CS-PCA-Arg, 45-90 parts of poloxamer 407, 3-6 parts of carbomer 940, and 6-12 parts of sodium hyaluronate. The resulting thermosensitive gel composition has good stability and can be used for the adjunctive treatment of radiation proctitis.
Description
Technical Field
The invention relates to the technical field of temperature-sensitive gel, in particular to a temperature-sensitive gel composition for auxiliary treatment of radiation proctitis and a preparation method thereof.
Background
Radiation proctitis (Radiation Proctitis, RP) refers to rectal complications caused by patients with malignant pelvic tumors when receiving radiotherapy or after radiotherapy, and erosion, ulceration or bleeding of the rectal mucosa can occur. Clinically, abdominal pain, diarrhea, hematochezia, mucopurulent bloody stool and the like seriously affect the life quality of patients. There are acute and chronic cases of radiation proctitis, depending on the severity of the illness. Most acute radiation proctitis occur 1-2 weeks after radiotherapy, and are mainly manifested by diarrhea, tenesmus, defecation pain, mucous stool, hematochezia, etc. About 80% of patients develop acute diarrhea during radiotherapy. Chronic patients often develop months to years after radiotherapy, and are manifested by rectal stenosis, difficult defecation, and even intestinal obstruction. At present, no ideal medicine and treatment method for radiation proctitis are available at home and abroad. In the actual clinical process, the treatment of radiation proctitis mainly adopts the modes of hormone, symptomatic support treatment and the like to relieve symptoms, but the curative effect is not ideal. Hormone therapy has the problems of strong dependence, long treatment course, multiple side effects and the like. Symptomatic treatments such as antibiotics, hemostatic drugs, film formers, etc. are unable to repair essentially damaged mucosa.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides a temperature-sensitive gel composition for auxiliary treatment of radiation proctitis and a preparation method thereof.
The invention is realized by the following technical scheme:
The temperature-sensitive gel composition for auxiliary treatment of radiation proctitis is prepared from the following components, by weight, 1.6-3.2 parts of curcumin@sodium alginate, 2-4 parts of CS-PCA-Arg, 45-90 parts of poloxamer 407, 3-6 parts of carbomer 940 and 6-12 parts of sodium hyaluronate.
Further, the curcumin@sodium alginate preparation raw material comprises, by weight, 2-3 parts of sialic acid, 1-1.5 parts of chitosan, 6-9 parts of sodium alginate and 1-1.5 parts of curcumin.
Further, the preparation method of the curcumin@sodium alginate comprises the following steps:
Dissolving chitosan in acetic acid solution with the concentration of 1% v/v to obtain CS solution, dissolving sialic acid in MES buffer with the concentration of 6, adding EDC, HCl and NHS, stirring for 30min, adding the mixture into the CS solution, stirring for reaction for 24h under the concentration of 6, dialyzing for 3d by deionized water, and performing vacuum freeze drying to obtain SA-chitosan;
Adding the SA-chitosan obtained in the step L1 and sodium alginate into distilled water, uniformly stirring, adding tween 80, uniformly mixing, adding curcumin, fully stirring, uniformly stirring by ultrasound, homogenizing at 4 ℃ and 10000 r/min for 30: 30min, dripping into 2wt% CaCl 2 solution, stirring at room temperature of 100: 100 r/min for 2h, centrifuging at 3000 r/min for 5: 5min, washing the precipitate with deionized water and ethanol, and vacuum drying to obtain curcumin@sodium alginate.
Further, in the step L1, the mass concentration of the chitosan in the acetic acid solution with the concentration of 1% v/v is 20 mg/mL.
Further, in step L1, the mass concentration of sialic acid in MES buffer is 20-30 mg/mL.
Further, in the step L1, the mass ratio of sialic acid to EDC & HCl to NHS is 4:3:1.8.
Further, in the step L2, the mass concentration of the sodium alginate in distilled water is 15 mg/mL.
Further, in step L2, the concentration of Tween 80 in distilled water was 0.5% v/v.
Further, in the step L2, the volume ratio of the CaCl 2 solution to the distilled water is 3:1.
Further, the CS-PCA-Arg preparation raw material comprises, by weight, 1.2-1.8 parts of chitosan, 0.4-0.6 part of protocatechuic acid and 0.5-0.8 part of arginine.
Further, the preparation method of the CS-PCA-Arg comprises the following steps:
Dissolving chitosan in acetic acid solution with the concentration of 1% V/V to obtain chitosan solution, dissolving EDC, HCl and NHS in MES buffer solution with the concentration of pH=5.5 to obtain EDC/NHS solution, dissolving protocatechuic acid in ethanol under nitrogen atmosphere, adding the ethanol into the EDC/NHS solution, stirring the solution in ice water bath in a dark place for 1h, adding the solution into the chitosan solution, stirring the solution in a dark place for 24h at room temperature, dialyzing the solution with deionized water for 2d, and performing vacuum freeze drying to obtain CS-PCA;
And V2, adding the CS-PCA obtained in the step V1 into acetic acid solution with the concentration of 1% V/V according to the proportion of 20 mg/mL under nitrogen atmosphere, stirring and uniformly mixing in a dark place to obtain a mixed solution A, dissolving arginine in MES buffer with the pH value of=5, adding EDC, HCl and NHS, stirring 2h to obtain a mixed solution B, adding the mixed solution B into the mixed solution A, stirring and reacting 24 h in a dark place, dialyzing 3d by deionized water, and freeze-drying to obtain CS-PCA-Arg.
Further, in the step V1, the mass concentration of the chitosan in the acetic acid solution with the concentration of 1% V/V is 20 mg/mL.
Further, in the step V1, the mass concentration of EDC & HCl in the MES buffer solution is 12.5 mg/mL.
Further, in the step V1, the mass concentration of the protocatechuic acid in the ethanol is 0.1 g/mL.
Further, in the step V1, the mass ratio of the protocatechuic acid, EDC & HCl and NHS is 0.4:0.5:0.3.
Further, in step V2, the arginine is present in the MES buffer at a mass concentration of 20 mg/mL.
Further, in the step V2, the mass ratio of the arginine EDC, HCl and NHS is 0.4:0.67:0.4.
Further, the invention also provides a preparation method of the thermosensitive gel composition for the adjuvant treatment of radiation proctitis, which comprises the following steps:
S1, adding CS-PCA-Arg into deionized water, performing ultrasonic treatment at room temperature of 300W to obtain 10 min, adding curcumin sodium alginate while stirring, stirring for 1 h to 200-300 rpm, filtering, washing with deionized water, and performing vacuum drying to obtain coated curcumin sodium alginate, and dispersing in deionized water according to the proportion of 50 mg/mL to obtain a dispersion;
s2, adding poloxamer 407 into deionized water, swelling overnight at 4 ℃ to obtain a component A, adding carbomer 940 into the deionized water, swelling overnight at 4 ℃, adding 5% triethanolamine solution, and uniformly stirring to obtain a component B;
and S3, mixing the component A, the component B and the component C obtained in the step S2, adding the dispersion liquid obtained in the step S1, and uniformly stirring to obtain the temperature-sensitive gel composition for auxiliary treatment of radiation proctitis.
Further, in step S1, the mass concentration of the CS-PCA-Arg in deionized water is 10 mg/mL.
Further, in step S2, the mass concentration of the poloxamer 407 in the deionized water is 0.45 g/mL.
Further, in step S2, the mass concentration of the carbomer 940 in deionized water is 60 mg/mL.
Further, in step S2, the mass concentration of the sodium hyaluronate in deionized water is 40 mg/mL.
Further, in step S2, the volume ratio of the triethanolamine solution to deionized water is 2:1.
Compared with the prior art, the invention has the following beneficial effects:
the invention provides a temperature-sensitive gel composition for auxiliary treatment of radiation proctitis and a preparation method thereof, and the composition combines the characteristics of temperature-sensitive gel through scientific proportioning and synergistic effect of specific components, so that the high-efficiency auxiliary treatment of radiation proctitis is realized, and meanwhile, good biological safety and stability are ensured. The chitosan is natural polysaccharide, has good biocompatibility and degradability, curcumin, protocatechuic acid, arginine and the like are all natural sources or substances with good biocompatibility, and poloxamer, carbomer and other materials are widely applied to medicinal preparations, so that the biological safety is high. According to the invention, the water-soluble and high-biocompatibility Sialic Acid (SA) is used for modifying Chitosan (CS) through EDC, HCl/NHS to prepare SA-chitosan, so that the water solubility of the chitosan is improved, SA-chitosan and sodium alginate are used as wall materials to encapsulate curcumin, and when the sodium alginate is crosslinked with Ca 2+, the SA-chitosan and the sodium alginate form a network structure, the SA-chitosan can fill surface pores, the leakage of the curcumin is reduced, the encapsulation rate of the curcumin is improved, and the storage stability is improved. The sodium alginate is natural anionic polysaccharide, and the prepared curcumin@sodium alginate has negative charges on the surface, so that the subsequent CS-PCA-Arg coating is facilitated. The curcumin is used as a natural active ingredient and has anti-inflammatory, antioxidant and mucosa repair potential, and the curcumin is encapsulated to prepare the curcumin@sodium alginate by using SA-chitosan and sodium alginate as wall materials and using curcumin as a core material, so that the auxiliary treatment effect can be improved. According to the invention, CS-PCA-Arg is prepared, protocatechuic acid is grafted on chitosan, protocatechuic acid is used as a natural phenolic compound, a catechol structure in molecules of the protocatechuic acid can effectively remove free radicals, arginine is further grafted on the basis of CS-PCA, the water solubility of the chitosan and the electropositivity of CS-PCA-Arg are enhanced, the affinity with the surface of curcumin@sodium alginate is improved, the protocatechuic acid can be effectively coated on the surface of curcumin@sodium alginate, and the positive charge in CS-PCA-Arg and the catechol group of protocatechuic acid can enhance the adhesion with intestinal tracts, promote the in-vivo retention effect, prolong the action time and promote the treatment effect. Meanwhile, the stability of the system is enhanced, and the leakage of curcumin is reduced. The temperature-sensitive gel can slowly release active ingredients such as curcumin after forming gel in rectum. Relieving inflammatory reaction of rectal mucosa, and promoting repair of mucosa.
Drawings
In order to more clearly illustrate the invention or the technical solutions of the prior art, the drawings which are used in the description of the embodiments or the prior art will be briefly described, it being obvious that the drawings in the description below are only of the invention and that other drawings can be obtained from them without inventive effort for a person skilled in the art.
Fig. 1 is a scanning electron microscope image of the coated curcumin@sodium alginate according to the embodiment 1 of the present invention;
FIG. 2 shows the curcumin encapsulation efficiency of curcumin@sodium alginate as described in examples 1-3 and comparative example 1 of the present invention;
FIG. 3 shows the stability of the coated curcumin@sodium alginate according to example 1 and comparative examples 2-3 of the present invention;
FIG. 4 shows the therapeutic effect of the temperature-sensitive gel according to example 1 and comparative examples 1 to 3 of the present invention.
Detailed Description
The present invention will be further described in detail with reference to the following specific examples, but the present invention is not limited to the following examples, for the purpose of making the objects, technical solutions and advantages of the present invention more apparent. Unless otherwise specified, the chemical reagents involved in the present invention are all commercially available.
The temperature-sensitive gel composition for the auxiliary treatment of the radiation proctitis comprises the following raw materials, by weight, 3.2 parts of curcumin@sodium alginate, 4 parts of CS-PCA-Arg, 407 parts of poloxamer 90, 940 parts of carbomer and 12 parts of sodium hyaluronate.
The curcumin@sodium alginate preparation raw material comprises the following components in parts by weight of 3 parts of sialic acid, 1.5 parts of chitosan, 9 parts of sodium alginate and 1.5 parts of curcumin.
The preparation method of curcumin@sodium alginate comprises the following steps:
Dissolving chitosan 1.5 g in acetic acid solution 75 mL with the concentration of 1%v/v to obtain CS solution, dissolving sialic acid 3g in MES buffer solution 100mL with the concentration of pH 6, adding EDC, HCl 2.25 g and NHS 1.35 g, stirring 30 min, adding into CS solution, stirring for reaction 24 h with the concentration of pH 6, dialyzing with deionized water to obtain 3d, and vacuum freeze-drying to obtain SA-chitosan;
Adding SA-chitosan obtained in the step L1 and sodium alginate 9 g into distilled water 600 mL, uniformly stirring, adding Tween 80 mL, uniformly mixing, adding curcumin 1.5 g, fully stirring, ultrasonically uniformly mixing, homogenizing at 4 ℃ and 10000 r/min for 30 min, dripping into 2wt% CaCl 2 solution 1800 mL, stirring at 100 r/min for 2h, centrifuging at 3000 r/min for 5 min, washing the precipitate with deionized water and ethanol, and vacuum drying to obtain curcumin@sodium alginate.
The CS-PCA-Arg preparation raw material comprises the following components in parts by weight of 1.8 parts of chitosan, 0.6 part of protocatechuic acid and 0.8 part of arginine.
The preparation method of CS-PCA-Arg comprises the following steps:
Dissolving chitosan 1.8 g in acetic acid solution 90 mL with the concentration of 1%v/V to obtain chitosan solution, dissolving EDC.HCl 0.75 g and NHS 0.45 g in MES buffer solution 60 mL with the concentration of pH=5.5 to obtain EDC/NHS solution, dissolving protocatechuic acid 0.6 g in ethanol 6 mL under nitrogen atmosphere, adding the EDC/NHS solution, stirring 1 h in ice water bath in dark place, adding the chitosan solution, stirring 24 h in dark place at room temperature, dialyzing 2d with deionized water, and performing vacuum freeze drying to obtain CS-PCA;
Under the atmosphere of nitrogen, adding the CS-PCA obtained in the step V1 into acetic acid solution with the concentration of 1% V/V according to the proportion of 20 mg/mL, stirring and mixing uniformly in a dark place to obtain a mixed solution A, dissolving arginine 0.8g into MES buffer solution 40 mL with the pH value of=5, adding EDC and HCl 1.34 g and NHS 0.8g, stirring 2h to obtain a mixed solution B, adding the mixed solution B into the mixed solution A, stirring and reacting 24: 24 h in a dark place, dialyzing with deionized water for 3: 3d, and freeze-drying to obtain CS-PCA-Arg.
The embodiment also provides a preparation method of the thermosensitive gel composition for the adjuvant therapy of radiation proctitis, which comprises the following steps:
S1, adding CS-PCA-Arg 4g into deionized water 400 mL, performing ultrasonic treatment at room temperature of 300W for 10min, adding 3.2 g of curcumin@sodium alginate while stirring, stirring at 300 rpm for 1 h, filtering, washing with deionized water, and vacuum drying to obtain coated curcumin@sodium alginate, wherein a scanning electron microscope image is shown in FIG. 1, and dispersing in deionized water according to a proportion of 50 mg/mL to obtain a dispersion;
S2, adding 407 g of poloxamer into 200 mL g of deionized water, swelling at 4 ℃ for overnight to obtain a component A, adding 940 g of carbomer into 100 mL g of deionized water, swelling at 4 ℃ for overnight, adding 200 mL of 5% triethanolamine solution, and uniformly stirring to obtain a component B, adding 12 g of sodium hyaluronate into 300 mL of deionized water, and swelling at 4 ℃ for overnight to obtain a component C;
and S3, mixing the component A, the component B and the component C obtained in the step S2, adding the dispersion liquid obtained in the step S1, and uniformly stirring to obtain the temperature-sensitive gel composition for auxiliary treatment of radiation proctitis.
Example 2A temperature-sensitive gel composition for auxiliary treatment of radiation proctitis is prepared from (by weight parts) curcumin @ sodium alginate 1.6, CS-PCA-Arg 2, poloxamer 407 45, carbomer 940 3, and sodium hyaluronate 6.
The curcumin@sodium alginate preparation raw material comprises the following components in parts by weight of 2 parts of sialic acid, 1 part of chitosan, 6 parts of sodium alginate and 1 part of curcumin.
The preparation method of curcumin@sodium alginate comprises the following steps:
Dissolving chitosan 1g in acetic acid solution 50mL with the concentration of 1%v/v to obtain CS solution, dissolving sialic acid 2g in MES buffer solution 100 mL with the concentration of pH 6, adding EDC and HCl 1.5g and NHS 0.9 g, stirring 30min, adding into CS solution, stirring for reaction 24 h with the concentration of pH 6, dialyzing with deionized water to obtain 3d, and vacuum freeze-drying to obtain SA-chitosan;
Adding SA-chitosan obtained in the step L1 and sodium alginate 6g into distilled water 400 mL, uniformly stirring, adding Tween 80 mL, uniformly mixing, adding curcumin 1g, fully stirring, uniformly stirring by ultrasound, dropwise adding into CaCl 2 solution 1200 mL with the concentration of 2wt%, stirring for 2 hours at room temperature of 100 r/min, centrifuging for 5 min at 3000 r/min, washing the precipitate with deionized water and ethanol, and vacuum drying to obtain curcumin@sodium alginate.
The CS-PCA-Arg preparation raw material comprises the following components in parts by weight of 1.2 parts of chitosan, 0.4 part of protocatechuic acid and 0.5 part of arginine.
The preparation method of CS-PCA-Arg comprises the following steps:
Dissolving chitosan 1.2 g in acetic acid solution 60 mL with the concentration of 1%v/V to obtain chitosan solution, dissolving EDC.HCl 0.5g and NHS 0.3 g in MES buffer solution 40 mL with the concentration of pH=5.5 to obtain EDC/NHS solution, dissolving protocatechuic acid 0.4 g in ethanol 4 mL under nitrogen atmosphere, adding the EDC/NHS solution, stirring 1h in ice water bath in dark place, adding the chitosan solution, stirring 24 h in dark place at room temperature, dialyzing 2d with deionized water, and performing vacuum freeze drying to obtain CS-PCA;
Under the atmosphere of nitrogen, adding the CS-PCA obtained in the step V1 into acetic acid solution with the concentration of 1% V/V according to the proportion of 20 mg/mL, stirring and mixing uniformly in a dark place to obtain a mixed solution A, dissolving arginine 0.5 g into MES buffer solution 25 mL with the pH value of=5, adding EDC and HCl 0.8375 g and NHS 0.5 g, stirring 2h to obtain a mixed solution B, adding the mixed solution B into the mixed solution A, stirring and reacting 24 h in a dark place, dialyzing 3d with deionized water, and freeze-drying to obtain CS-PCA-Arg.
The embodiment also provides a preparation method of the thermosensitive gel composition for the adjuvant therapy of radiation proctitis, which comprises the following steps:
s1, adding CS-PCA-Arg 2g into deionized water 200 mL, performing ultrasonic treatment at room temperature of 300W for 10 min, adding curcumin@sodium alginate 1.6 g while stirring at 200 rpm for 1 h, filtering, washing with deionized water, and performing vacuum drying to obtain coated curcumin@sodium alginate, and dispersing in deionized water according to the proportion of 50 mg/mL to obtain a dispersion;
S2, adding 407 g of poloxamer into 100mL g of deionized water, swelling at 4 ℃ for overnight to obtain a component A, adding 940 g of carbomer into 50 mL g of deionized water, swelling at 4 ℃ for overnight, adding 100mL of 5% triethanolamine solution, and uniformly stirring to obtain a component B, adding 6 g of sodium hyaluronate into 150 mL g of deionized water, and swelling at 4 ℃ for overnight to obtain a component C;
and S3, mixing the component A, the component B and the component C obtained in the step S2, adding the dispersion liquid obtained in the step S1, and uniformly stirring to obtain the temperature-sensitive gel composition for auxiliary treatment of radiation proctitis.
Example 3A temperature-sensitive gel composition for auxiliary treatment of radiation proctitis is prepared from (by weight parts) curcumin @ sodium alginate 2.4, CS-PCA-Arg 3, poloxamer 407.5, carbomer 940 4.5, and sodium hyaluronate 9.
The curcumin@sodium alginate preparation raw material comprises the following components in parts by weight of 2.5 parts of sialic acid, 1.25 parts of chitosan, 7.5 parts of sodium alginate and 1.25 parts of curcumin.
The preparation method of curcumin@sodium alginate comprises the following steps:
Dissolving chitosan 1.25 g in acetic acid solution 62.5 mL with the concentration of 1%v/v to obtain CS solution, dissolving sialic acid 2.5 g in MES buffer solution 100 mL with the concentration of pH 6, adding EDC & HCl 1.875 g and NHS 1.125 g, stirring 30min, adding into CS solution, stirring for reaction 24h with the concentration of pH 6, dialyzing with deionized water 3d, and vacuum freeze-drying to obtain SA-chitosan;
Adding SA-chitosan obtained in the step L1 and sodium alginate 7.5 g into distilled water 500 mL, uniformly stirring, adding Tween 80.5 mL, uniformly mixing, adding curcumin 1.25 g, fully stirring, ultrasonically uniformly mixing, homogenizing at 4 ℃ and 10000 r/min for 30 min, dropwise adding 2wt% CaCl 2 solution 1500 mL, stirring at 100 r/min for 2h, centrifuging at 3000 r/min for 5 min, washing the precipitate with deionized water and ethanol, and vacuum drying to obtain curcumin@sodium alginate.
The CS-PCA-Arg preparation raw material comprises the following components in parts by weight of 1.5 parts of chitosan, 0.5 part of protocatechuic acid and 0.6 part of arginine.
The preparation method of CS-PCA-Arg comprises the following steps:
Dissolving chitosan 1.5g in acetic acid solution 75 mL with the concentration of 1%v/V to obtain chitosan solution, dissolving EDC.HCl 0.625. 0.625 g and NHS 0.375. 0.375 g in MES buffer solution 50 mL with the concentration of pH=5.5 to obtain EDC/NHS solution, dissolving protocatechuic acid 0.5g in ethanol 5mL under nitrogen atmosphere, adding the EDC/NHS solution, stirring 1 h in ice water bath in dark place, adding the chitosan solution, stirring 24 h in dark place at room temperature, dialyzing 2 d with deionized water, and performing vacuum freeze drying to obtain CS-PCA;
Under the atmosphere of nitrogen, adding the CS-PCA obtained in the step V1 into acetic acid solution with the concentration of 1% V/V according to the proportion of 20 mg/mL, stirring and mixing uniformly in a dark place to obtain a mixed solution A, dissolving arginine 0.6 g into MES buffer solution 30 mL with the pH value of=5, adding EDC and HCl 1.005 g and NHS 0.6 g, stirring 2 h to obtain a mixed solution B, adding the mixed solution B into the mixed solution A, stirring and reacting 24: 24 h in a dark place, dialyzing with deionized water for 3: 3d, and freeze-drying to obtain CS-PCA-Arg.
The embodiment also provides a preparation method of the thermosensitive gel composition for the adjuvant therapy of radiation proctitis, which comprises the following steps:
S1, adding CS-PCA-Arg 3g into deionized water 300 mL, performing ultrasonic treatment at room temperature of 300W for 10min, adding curcumin@sodium alginate 2.4 g while stirring at 250rpm for stirring for 1 h, filtering, washing with deionized water, and performing vacuum drying to obtain coated curcumin@sodium alginate, and dispersing in deionized water according to the proportion of 50 mg/mL to obtain a dispersion;
S2, adding 67.5 g of poloxamer 407 into 150 mL of deionized water, swelling at 4 ℃ for overnight to obtain a component A, adding 940.5 g of carbomer into 75 mL of deionized water, swelling at 4 ℃ for overnight, adding 5% of triethanolamine solution, stirring 150 and mL, and uniformly stirring to obtain a component B, adding 9 g of sodium hyaluronate into 225 mL of deionized water, and swelling at 4 ℃ for overnight to obtain a component C;
and S3, mixing the component A, the component B and the component C obtained in the step S2, adding the dispersion liquid obtained in the step S1, and uniformly stirring to obtain the temperature-sensitive gel composition for auxiliary treatment of radiation proctitis.
Comparative example 1 differs from example 1 only in that no SA-chitosan was added.
Comparative example 2 differs from example 1 only in that no arginine was added.
Comparative example 3 differs from example 1 only in that no catechin was added.
Experimental example 1 curcumin @ sodium alginate was prepared in the same manner as in examples 1-3 and comparative example 1, the obtained product 0.01 g was added to 1.5 mL absolute ethanol, and the mixture was put into a freeze mill, ground at-20 deg.C to 5min, sonicated to 10min, the supernatant was collected by centrifugation, a suitable amount of absolute ethanol was used to wash the precipitate, the washing solution was mixed with the supernatant, the curcumin content m1 was measured, and the curcumin encapsulation efficiency was calculated, wherein the encapsulation efficiency (%) = (m 1/m) ×100% and m was the curcumin dose. The results are shown in FIG. 2.
The results of fig. 2 show that the curcumin encapsulation efficiency of the examples 1-3 is significantly better than that of the comparative example 1, and the curcumin encapsulation efficiency is reduced in the comparative example 1 without adding SA-chitosan, which indicates that the SA-chitosan prepared by the invention can effectively improve the encapsulation efficiency of active ingredients.
Experimental example 2 coated curcumin @ sodium alginate was prepared in the same manner as in example 1 and comparative examples 2 to 3, the encapsulation efficiency was measured, and the coated curcumin @ sodium alginate was left at room temperature, and the encapsulation efficiency was measured again with the 7 th, 14 th, 30 th, 60 th and 90 d th, respectively, and the retention of encapsulation efficiency was calculated, and the retention of encapsulation efficiency (%) = (encapsulation efficiency after placement/encapsulation efficiency before placement) ×100%. The results are shown in FIG. 3.
The results of fig. 3 show that the retention rate of the encapsulation efficiency of example 1 is significantly better than that of comparative examples 2-3, the comparative example 2 has no arginine grafted on the chitosan, the coating effect on curcumin@sodium alginate is reduced, the stability of the prepared coated curcumin@sodium alginate is reduced, and the retention rate of the encapsulation efficiency is reduced.
Experimental example 3A radiation proctitis model was established by irradiation with 6MV-X rays, first, female SD rats (6-8 weeks old, weight 180g-220 g) were anesthetized by intraperitoneal injection of sodium pentobarbital (40 mg/kg), the rats were supine fixed on a plate, the irradiation range was adjusted from pubic symphysis to anus, the irradiation field area was 4 cm. Times.3 cm, the source skin distance was 100 cm, the irradiation dose was 25Gy, and the dose rate was 400 cGy// min. After molding, rats had reduced eating and drinking water, and were discharged with mucous stool, thin stool and bloody stool, and success of molding was evaluated. The rats successfully molded were randomly divided into 5 groups of 7 rats each, which were respectively a model group, an example 1 group and a comparative example 1-3 groups, and a blank group (7 rats) without molding was additionally provided, and the rats were administered by a rectal administration device on day 2, at a rectal position of the anus 3cm, 1.5 mL thermosensitive gel compositions were respectively administered in the example 1 and comparative example 1-3 groups, and the model group and the blank group were administered with an equivalent amount of physiological saline, and the surrounding of the anus of the SD rats was stimulated with a cotton swab before enema every day, so that the SD rats were emptied as much as possible. Once daily, and 14 d is administered continuously. Rats were sacrificed in a cervical-removal manner, the rectocele tissues were HE stained, the histopathological changes were observed with an optical microscope, the rectal pathological states were graded according to the radiological proctitis pathological states of the rats, and the rectal pathological injury scores were calculated. Grade 0, normal rectal mucosa, grade 1, very slight injury, very slight rectal inflammation and/or very slight rectal gland injury, grade 1, grade 2, lower injury, rectal inflammation or gland change more obvious than grade 1, grade 2, grade 3, moderate injury, obvious rectal epithelial shedding, grade 3, grade 4, severe injury, occurrence of ulcer or necrosis, grade 4. The blank set had a score of 0 and the model set, example 1 set, and comparative examples 1-3 set were scored as shown in figure 4.
The results of fig. 4 show that the scores of the groups 1 and 3 are significantly lower than that of the model group, which indicates that the temperature-sensitive gel composition prepared by the invention can be effectively used for auxiliary treatment of radiation proctitis, and the temperature-sensitive gel composition can be retained in rats, so that the drug effect is prolonged and the treatment effect is improved.
It will be appreciated by persons skilled in the art that the above discussion of any embodiment is merely exemplary and is not intended to imply that the scope of the invention is limited to these examples, that combinations of technical features in the above embodiments or in different embodiments may also be implemented in any order, and that many other variations of the different aspects of the invention as described above exist, which are not provided in detail for the sake of brevity.
Claims (7)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202511335505.8A CN120815035B (en) | 2025-09-18 | 2025-09-18 | Temperature-sensitive gel composition for auxiliary treatment of radiation proctitis and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202511335505.8A CN120815035B (en) | 2025-09-18 | 2025-09-18 | Temperature-sensitive gel composition for auxiliary treatment of radiation proctitis and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN120815035A true CN120815035A (en) | 2025-10-21 |
| CN120815035B CN120815035B (en) | 2025-11-14 |
Family
ID=97370535
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202511335505.8A Active CN120815035B (en) | 2025-09-18 | 2025-09-18 | Temperature-sensitive gel composition for auxiliary treatment of radiation proctitis and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN120815035B (en) |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070237811A1 (en) * | 2006-04-10 | 2007-10-11 | Scherr George H | Chitosan wound dressing |
| CN102406594A (en) * | 2011-12-02 | 2012-04-11 | 常州市第一人民医院 | A kind of curcumin nasal gel and its preparation method and application |
| WO2014064121A2 (en) * | 2012-10-25 | 2014-05-01 | Unilever Plc | Improvements relating to surface treatment compositions |
| CN114522138A (en) * | 2022-01-27 | 2022-05-24 | 安徽大学 | Preparation method and application of curcumin-loaded Pickering emulsion gel |
| CN115025040A (en) * | 2022-06-16 | 2022-09-09 | 湖南迈格生物医药有限责任公司 | Temperature-sensitive gel for relieving dysphagia and sternal pain after eating of patients with esophageal cancer and preparation method thereof |
| CN116510066A (en) * | 2023-04-07 | 2023-08-01 | 华南理工大学 | Temperature-sensitive transition point adjustable drug slow-release carrier hydrogel and preparation method thereof |
| CN117084968A (en) * | 2023-08-21 | 2023-11-21 | 上海萌凯医药科技有限公司 | Temperature-sensitive gel for treating radiation proctitis and preparation process thereof |
| US20250213592A1 (en) * | 2022-02-10 | 2025-07-03 | Corestemchemon Inc. | Pharmaceutical composition comprising curcumin and ginsenoside, and formulation thereof |
-
2025
- 2025-09-18 CN CN202511335505.8A patent/CN120815035B/en active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070237811A1 (en) * | 2006-04-10 | 2007-10-11 | Scherr George H | Chitosan wound dressing |
| CN102406594A (en) * | 2011-12-02 | 2012-04-11 | 常州市第一人民医院 | A kind of curcumin nasal gel and its preparation method and application |
| WO2014064121A2 (en) * | 2012-10-25 | 2014-05-01 | Unilever Plc | Improvements relating to surface treatment compositions |
| CN114522138A (en) * | 2022-01-27 | 2022-05-24 | 安徽大学 | Preparation method and application of curcumin-loaded Pickering emulsion gel |
| US20250213592A1 (en) * | 2022-02-10 | 2025-07-03 | Corestemchemon Inc. | Pharmaceutical composition comprising curcumin and ginsenoside, and formulation thereof |
| CN115025040A (en) * | 2022-06-16 | 2022-09-09 | 湖南迈格生物医药有限责任公司 | Temperature-sensitive gel for relieving dysphagia and sternal pain after eating of patients with esophageal cancer and preparation method thereof |
| CN116510066A (en) * | 2023-04-07 | 2023-08-01 | 华南理工大学 | Temperature-sensitive transition point adjustable drug slow-release carrier hydrogel and preparation method thereof |
| CN117084968A (en) * | 2023-08-21 | 2023-11-21 | 上海萌凯医药科技有限公司 | Temperature-sensitive gel for treating radiation proctitis and preparation process thereof |
Non-Patent Citations (2)
| Title |
|---|
| S.E. KIM等: "P183 Therapeutic Effects of Curcumin and Ginsenoside Combination in a Animal Model of Radiation Proctitis", JOURNAL OF CROHN\'S AND COLITIS, vol. 18, no. 1, 31 January 2024 (2024-01-31), pages 487 * |
| 谢亚琳等: "磷酸铝凝胶、白细胞介素11、地塞米松保留灌肠防治急性放射性直肠炎效果观察", 山东医药, vol. 55, no. 8, 27 February 2015 (2015-02-27), pages 39 - 40 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN120815035B (en) | 2025-11-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6036977A (en) | Drug preparations for treating sexual dysfunction | |
| JP2002511057A (en) | Topical drug formulation | |
| CN113712902B (en) | Injectable hydrogel loaded with active oxygen response degradable polymer micelle and preparation method and application thereof | |
| CN1346252A (en) | Extended-release bioadhesive vaginal gel dosage form | |
| JP2002524408A (en) | Formulations for treating sexual dysfunction | |
| JP2002537070A (en) | Bioadhesive antimicrobial wound healing composition | |
| JP2002513410A (en) | Drug formulations for treating sexual dysfunction | |
| CN108210689A (en) | A kind of canker sore film containing hyaluronic acid and preparation method thereof | |
| CN120815035B (en) | Temperature-sensitive gel composition for auxiliary treatment of radiation proctitis and preparation method thereof | |
| CN103191408B (en) | Medicine composition and gel for treating colpitis and applications thereof | |
| CN1169838C (en) | Acetylmannan and its preparation method and application | |
| CN115998840A (en) | Composition containing polypeptide substances, and preparation method, preparation and application thereof | |
| CN109157529A (en) | A kind of preparation method of Enoxaparin Sodium microballoon | |
| EP3222270A1 (en) | Compositions for mucosal adhesion and uses thereof | |
| CN1167446C (en) | A traditional Chinese medicine gel for treating cervicitis and cervical erosion and its preparation method | |
| JP2000256182A (en) | Antimicrobial formulation | |
| IL295822A (en) | Topical compositions designed to maintain and/or restore the integrity of the mucosa and damaged epidermis | |
| CN1478485A (en) | Liposome ointment containing heparin drugs and preparation method thereof | |
| CN116650403B (en) | Metronidazole gel and preparation method and application thereof | |
| CN114983982B (en) | A kind of sustained-release oral ulcer hydrogel ulcer patch | |
| CN119454607A (en) | Drug-loaded hydrogel powder, preparation method and application thereof | |
| CN120025966B (en) | Pulsatillae vesicle, preparation method thereof and application thereof in intestinal inflammation | |
| CN109999046A (en) | A kind of Poria cocos oligosaccharides and its preparation method and application | |
| CN121059516A (en) | A gamboge acid hydrogel formulation, its preparation method and application | |
| EP4204010A1 (en) | Sol-gel composition |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |