CN108815381B - Traditional Chinese medicine silver titanate composite porous material for burn wound healing and preparation method and application thereof - Google Patents

Traditional Chinese medicine silver titanate composite porous material for burn wound healing and preparation method and application thereof Download PDF

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CN108815381B
CN108815381B CN201810606833.0A CN201810606833A CN108815381B CN 108815381 B CN108815381 B CN 108815381B CN 201810606833 A CN201810606833 A CN 201810606833A CN 108815381 B CN108815381 B CN 108815381B
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traditional chinese
porous material
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CN108815381A (en
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苏永华
张慧卿
张丞
杨葛亮
苟浩
韩梦飞
黄若尘
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Shanghai Changhai Hospital
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/898Orchidaceae (Orchid family)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716Glucans
    • A61K31/722Chitin, chitosan
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/24Heavy metals; Compounds thereof
    • A61K33/38Silver; Compounds thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/02Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like

Abstract

The invention discloses a traditional Chinese medicine silver titanate composite porous material for healing burn wounds, which is prepared from a baicalin solution, a bletilla rubber cement solution and a carboxymethyl chitosan cement solution in a volume ratio of 1:1 (1-5), wherein: the concentration of the baicalin solution is 100mg/mL, the concentration of the bletilla gum solution is 5%, and the concentration of the carboxymethyl chitosan gum solution is 4%; the loading amount of the silver titanate is 0.1-5 wt%. The invention also discloses application of the traditional Chinese medicine silver titanate composite porous material for healing the burn wound in preparation of a burn wound healing medicine. The traditional Chinese medicine silver titanate composite porous material for healing burn wounds, which is prepared by the invention, has no skin irritation, good antibacterial property, water absorption and air permeability, and has an obvious healing promotion effect on burn wounds.

Description

Traditional Chinese medicine silver titanate composite porous material for burn wound healing and preparation method and application thereof
Technical Field
The invention belongs to the technical field of medical materials, and particularly relates to a traditional Chinese medicine silver titanate composite porous material for healing burn wounds, and a preparation method and application thereof.
Background
Burns are common injuries in daily life, and the incidence of burns in warts is increasing. Therefore, the research on the burn treatment has important social and military significance. The key to burn wound treatment is infection resistance and healing promotion. The traditional Chinese medicine has good treatment effects on relieving wound pain, resisting infection, promoting wound healing, reducing scar formation, enhancing immunity conditioning and the like. However, the traditional Chinese medicine dosage form cannot meet the application requirements of modern clinical and battlefield environments. Therefore, the construction of a novel burn wound treatment material which combines the traditional Chinese medicine and the modern preparation technology and has dual effects of resisting infection and promoting wound tissue regeneration has important significance.
The scutellaria baicalensis is one of the traditional Chinese medicines commonly used for treating burn in clinic, and the main pharmacological active ingredient of the scutellaria baicalensis is baicalin. Baicalin has an o-diphenol hydroxyl structure, shows remarkable antioxidant activity, and can reduce inflammatory reaction after skin injury by removing hydroxyl free radicals and alkyl free radicals. The baicalin has wide antibacterial spectrum, has obvious inhibiting effect on pseudomonas aeruginosa, staphylococcus, streptococcus, diplococcus pneumoniae, meningococcus and the like, and can inhibit the occurrence of bacterial drug resistance. It can induce the expression of Vascular Endothelial Growth Factor (VEGF) by activating the estradiol receptor (ERR alpha) pathway, promoting angiogenesis. Inhibits the proliferation of human hypertrophic scar tissue fibroblasts by inhibiting a PI3K/Akt/mTOR signaling pathway.
The bletilla striata is a traditional Chinese medicine which is commonly used in clinic and can promote wound healing, the main effective component of the bletilla striata is bletilla striata gum polysaccharide, the bletilla striata gum polysaccharide is viscous polysaccharide and is polymerized by various micromolecule saccharides, and the bletilla striata is non-toxic and irritant, has no antigenicity and pyrogenicity, has good tissue compatibility and is an excellent natural polymer film-forming material. The bletilla striata gum has good healing promoting and antioxidant effects on wound surfaces of ulcer, burn and the like. Modern researches show that the bletilla striata gum can promote the expression of Epidermal Growth Factor (EGF) and Epidermal Growth Factor Receptor (EGFR), reduce the expression of tumor necrosis factor (TNF-alpha) and achieve the effect of promoting tissue healing. The bletilla striata gum can also regulate the JAK2 expression level of a JAK/STAT signal channel, inhibit the release of downstream inflammatory factors such as tumor necrosis factor (TNF-alpha), interleukin-6 (IL-6), interleukin-8 (IL-8) and the like, and has a protective effect on cobalt chloride induced Human keratinocyte (Human Keratinocytes, HKC) oxidative stress and inflammatory injury in vitro models.
The nano-silver dressing is widely used for treating burn wounds in recent years as a novel antibacterial material. The silver titanate has broad-spectrum antibacterial activity, can be uniformly and firmly attached to the dressing, can continuously release silver ions after contacting with the wound surface, and maintains long-term antibacterial activity.
Carboxymethyl chitosan is a widely used high molecular film forming material, and has good water solubility, biocompatibility, biodegradability, high moisture retention capacity and oxidation resistance due to no toxicity, so that the carboxymethyl chitosan has research and application in the fields of in vitro diagnosis and treatment, wound repair, gene therapy, food technology and the like.
Chinese patent document CN104784743A discloses a preparation method of an aromatic bacteriostatic chitosan-based wound dressing, which comprises the steps of mixing tea tree essential oil, menthol and folium artemisiae argyi essential oil according to a certain proportion to prepare a natural aromatic bacteriostatic agent, coating the natural aromatic bacteriostatic agent in liposome to obtain aromatic bacteriostatic liposome, dispersing the aromatic bacteriostatic liposome in chitosan-sodium alginate-gelatin solution, and freeze-drying according to a certain program to obtain the aromatic bacteriostatic chitosan-based wound dressing. The wound dressing disclosed in this patent is a porous structure, has certain slow-release antibacterial, hemostatic, water-absorbing and air-permeable properties, but has no effect of promoting wound healing and no drug composition.
Chinese patent document CN104436284A discloses a fibroin porous material loaded with insulin/fibroin microspheres and a preparation method thereof, the method adopts a coaxial high-voltage electrostatic technology and a freeze-drying method to prepare the fibroin microspheres loaded with insulin, and adopts a layer-by-layer assembly and freeze-drying method to prepare the fibroin/fibroin microsphere-loaded porous material, the fibroin porous material loaded with insulin/fibroin microspheres disclosed by the patent can stimulate epidermal cells and endothelial cells to move, and the wound healing speed is promoted. However, it has no bacteriostatic activity and anti-infection function, and cannot cope with the characteristic of easy infection of burn wound.
The traditional Chinese medicine and modern medical dressing technology are combined, and the bletilla striata glue and the carboxymethyl chitosan are used as high molecular film forming materials to prepare the traditional Chinese medicine-silver titanate composite porous material for healing the burn wound surface, which is not reported.
Disclosure of Invention
The invention aims to provide a traditional Chinese medicine silver titanate composite porous material for healing burn wounds, and the obtained porous material has obvious bacteriostatic activity and wound healing promotion capability.
The invention also aims to provide a preparation method of the traditional Chinese medicine silver titanate composite porous material for healing burn wounds.
The invention also aims to provide application of the traditional Chinese medicine silver titanate composite porous material for healing the burn wound in preparation of a burn wound healing medicine.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
the invention provides a traditional Chinese medicine silver titanate composite porous material for healing burn wounds, which is prepared from a baicalin solution, a bletilla rubber cement solution and a carboxymethyl chitosan rubber cement in a volume ratio of 1:1 (1-5), wherein: the concentration of the baicalin solution is 100mg/mL, the concentration of the bletilla gum solution is 5%, and the concentration of the carboxymethyl chitosan gum solution is 4%; the loading amount of the silver titanate is 0.1-5 wt%.
The traditional Chinese medicine silver titanate composite porous material for healing the burn wound surface is prepared from a baicalin solution, a bletilla rubber cement solution and a carboxymethyl chitosan rubber cement solution in a volume ratio of 1:1: 3.
The loading of the silver titanate is 1 wt%.
The second aspect of the invention provides a preparation method of the traditional Chinese medicine silver titanate composite porous material for healing burn wounds, which comprises the following steps:
mixing the baicalin solution, the bletilla striata gum solution and the carboxymethyl chitosan gum according to the proportion, reacting for 0.1-2 h at the temperature of 40-85 ℃, fully crosslinking until no bubbles exist, dripping the mixed gum solution into a 24-pore plate, adding 0.6mL of liquid into each pore, cooling to room temperature, and then adding silver titanate, wherein the concentration of the silver titanate in the 24-pore plate is 0.8-0.9 mg/mL; pre-freezing the 24-pore plate, and then carrying out vacuum freeze drying to obtain the traditional Chinese medicine silver titanate composite porous material for healing the burn wound.
The concentration of the silver titanate in the 24-well plate is 0.83 mg/mL.
The preparation method of the silver titanate comprises the following steps:
mixing tetrabutyl titanate with the volume ratio of (8-9): 1 and hydrofluoric acid with the concentration of 40%, carrying out hydrothermal treatment for 1-48 h at 160-200 ℃, then adding silver nitrate with the intermediate mass of 0.5-1% into the intermediate, carrying out ultraviolet light photo-deposition for 1-60 min, and carrying out vacuum freeze-drying to obtain the silver titanate.
The volume ratio of the tetrabutyl titanate to the hydrofluoric acid with the concentration of 40 percent is 50/6.
The pre-freezing temperature is-10 to-30 ℃, and the time is 1 to 48 hours.
The pre-freezing temperature is-20 ℃ and the time is 24 h.
The vacuum freeze-drying conditions are as follows: the temperature is-10 to-40 ℃, the pressure is 0.07 to 1.0mBar, and the time is 1 to 48 hours.
The vacuum freeze-drying conditions are as follows: the temperature is-20 ℃, the pressure is 1.0mBar, and the time is 12 h.
The third aspect of the invention provides application of the traditional Chinese medicine silver titanate composite porous material for healing the burn wound in preparation of a burn wound healing medicine.
Due to the adoption of the technical scheme, the invention has the following advantages and beneficial effects:
the traditional Chinese medicine silver titanate composite porous material for healing burn wounds, which is prepared by the invention, has no skin irritation, good antibacterial property, water absorption and air permeability, and has an obvious healing promotion effect on burn wounds.
The traditional Chinese medicine silver titanate composite porous material for healing the burn wound combines the traditional Chinese medicine with the modern medical dressing technology, baicalin and silver titanate provide continuous antibacterial activity, and the common bletilla gum has good adhesiveness and the performance of promoting the wound healing, and has good anti-infection and healing promoting effects on the burn wound.
The traditional Chinese medicine silver titanate composite porous material for healing the burn wound uses the bletilla striata glue and the carboxymethyl chitosan as high-molecular film forming materials, the bletilla striata glue plays a role of a cross-linking agent, a chemical cross-linking agent is not needed, and toxicity and irritation of the chemical cross-linking agent are avoided.
The traditional Chinese medicine silver titanate composite porous material for healing burn wounds, which is prepared by the invention, has a spongy porous structure, is soft in texture, good in water absorption and air permeability, and strong in adhesiveness after being wetted, can be directly applied to wounds with more exudation, is increased in adhesiveness after absorbing exudates, is not easy to fall off, does not need adhesive tape fixation, increases air permeability, and prevents adhesive tape allergy. For the wound surface with less exudation, the composite porous material can be applied after the wound surface is cleaned and moistened by normal saline. The characteristic is very suitable for the requirement of quickly and efficiently treating the burn wound surface no matter in a hard battlefield environment or in daily life.
Drawings
Fig. 1 is a schematic view of the traditional Chinese medicine silver titanate composite porous material for healing of burn wounds prepared in example 1.
Fig. 2 is a scanning electron microscope (SEM 200X) image of the traditional Chinese medicine silver titanate composite porous material for burn wound healing prepared in example 2.
Fig. 3 is a scanning electron microscope (SEM 1000X) image of the traditional Chinese medicine silver titanate composite porous material for burn wound healing prepared in example 2.
Fig. 4 is a scanning electron microscope (SEM 3000X) of the traditional Chinese medicine silver titanate composite porous material for burn wound healing prepared in example 2.
Fig. 5 is a graph showing the results of the skin irritation test of the traditional Chinese medicine silver titanate composite porous material for healing of burn wounds on damaged skin groups, prepared in example 2.
Fig. 6 is a graph showing the results of the skin irritation test of the traditional Chinese medicine silver titanate composite porous material for healing of burn wounds on a normal skin group, prepared in example 2.
Fig. 7 is a statistical result chart of wound healing rate of the traditional Chinese medicine silver titanate composite porous material for burn wound healing prepared in example 2.
Detailed Description
In order to more clearly illustrate the invention, the invention is further described below in connection with preferred embodiments. It is to be understood by persons skilled in the art that the following detailed description is illustrative and not restrictive, and is not to be taken as limiting the scope of the invention.
Example 1
Screening of proportion of bletilla striata gum and carboxymethyl chitosan in traditional Chinese medicine silver titanate composite porous material for burn wound healing
Pulverizing rhizoma Bletillae decoction pieces, soaking in 7 times of distilled water for 12 hr, stirring, and filtering to obtain filtrate. Soaking the residue in 4 times of water for 3 times, each time for 6 hr, and filtering. The 4 filtrates were combined and concentrated to a relative density of 1.10(65 ℃). Cooling, adding 95% ethanol to ethanol content of 70%, stirring to precipitate a large amount of floccule, standing, vacuum filtering to dry, adding ethanol into the precipitate, stirring, standing, dehydrating for 3 times, filtering to dry, volatilizing ethanol, oven drying at low temperature, and slightly grinding to obtain yellowish brown dry powder rhizoma Bletillae polysaccharide, i.e. rhizoma Bletillae gum. The purity is detected to be more than or equal to 85 percent (Pentium, the research of gelatin/bletilla hyacinthine gum drug-loaded porous material and the influence on wound healing [ D ] Huazhong university of science and technology, 2005).
Weighing 1.176g of the bletilla striata gum powder, adding 18.824mL of double distilled water, fully mixing, placing in a water bath at 55 ℃, stirring to fully expand, standing, and centrifuging to remove precipitate to obtain 5% bletilla striata gum solution.
2g of carboxymethyl chitosan (Shanghai Chunlu biochemistry Co., Ltd.) was weighed, added to 48mL of double distilled water, and mixed thoroughly, and stirred to dissolve completely, to obtain 4% carboxymethyl chitosan colloidal solution.
Weighing 2g baicalin (Shanghai Baomann Biotechnology Co., Ltd.), adding 15mL double distilled water to dissolve, stirring thoroughly, placing in 85 deg.C water bath, and adjusting pH to 7.5 with 1mol/L NaOH solution. Then adding double distilled water to reach the constant volume of 20mL to obtain a baicalin solution of 100 mg/mL.
Mixing baicalin solution 1mL with concentration of 100mg/mL, rhizoma Bletillae gelatin solution 9mL with concentration of 5%, and carboxymethyl chitosan gelatin solution 1mL with concentration of 4%, placing in water bath at 55 deg.C for 30min, fully crosslinking, and stirring until no bubble exists. The mixed gel after the crosslinking reaction was dropped into the No. 1 well of the 6-well plate, and 1.5mL of the solution was added.
Mixing baicalin solution 1mL with concentration of 100mg/mL, rhizoma Bletillae gelatin solution 5mL with concentration of 5%, and carboxymethyl chitosan gelatin solution 1mL with concentration of 4%, placing in water bath at 55 deg.C for 30min, fully crosslinking, and stirring until no bubble exists. The mixed gel after the crosslinking reaction is dripped into No. 2 hole of a 6-hole plate, and 1.5mL of liquid is added.
Mixing baicalin solution 1mL with concentration of 100mg/mL, rhizoma Bletillae gelatin solution 3mL with concentration of 5%, and carboxymethyl chitosan gelatin solution 1mL with concentration of 4%, placing in water bath at 55 deg.C for 30min, fully crosslinking, and stirring until no bubble exists. The mixed gel after the crosslinking reaction is dripped into No. 3 hole of a 6-hole plate, and 1.5mL of liquid is added.
Mixing baicalin solution 1mL with concentration of 100mg/mL, rhizoma Bletillae gelatin solution 1mL with concentration of 5%, and carboxymethyl chitosan gelatin solution 1mL with concentration of 4%, placing in water bath at 55 deg.C for 30min, fully crosslinking, and stirring until no bubble exists. The mixed gel after the crosslinking reaction was dropped into No. 4 well of a 6-well plate, and 1.5mL of the solution was added.
Mixing baicalin solution 1mL with concentration of 100mg/mL, rhizoma Bletillae gelatin solution 1mL with concentration of 5%, and carboxymethyl chitosan gelatin solution 3mL with concentration of 4%, placing in water bath at 55 deg.C for 30min, fully crosslinking, and stirring until no bubble exists. The mixed gel after the crosslinking reaction is dripped into No. 5 holes of a 6-hole plate, and 1.5mL of liquid is added.
Mixing baicalin solution 1mL with concentration of 100mg/mL, rhizoma Bletillae gelatin solution 1mL with concentration of 5%, and carboxymethyl chitosan gelatin solution 5mL with concentration of 4%, placing in water bath at 55 deg.C for 30min, fully crosslinking, and stirring until no bubble exists. The mixed gel after the crosslinking reaction is dripped into No. 6 holes of a 6-hole plate, and 1.5mL of liquid is added.
And cooling the 6-hole plate to room temperature, and pre-freezing the plate in a refrigerator at the temperature of-20 ℃ for 24 hours. Then placing the mixture in a vacuum freeze dryer, and freeze-drying the mixture for 12 hours at the temperature of minus 20 ℃ and under the pressure of 1.0 mBar.
The properties of texture, elasticity, flexibility, porous structure, etc. of the porous material produced in the 6-well plate were observed, as shown in table 1.
TABLE 1 porous Material Properties of bletilla Gum and carboxymethyl Chitosan in different proportions
Figure BDA0001694556070000051
Figure BDA0001694556070000061
As shown in table 1 and fig. 1, fig. 1 is a schematic diagram of the traditional Chinese medicine silver titanate composite porous material for healing burn wounds prepared in example 1, and materials prepared from 6 different proportions of bletilla striata gum and carboxymethyl chitosan all have a porous structure, strong water absorption and viscosity after wetting. But when the content of the 5% of common bletilla gum liquid is as follows: when the liquid volume ratio of the 4% carboxymethyl chitosan glue is 9:1, 5:1 and 3:1, the prepared material has large cracks, is dry, hard and brittle, and indicates that the crosslinking is insufficient, the pores are not uniform, and bubbles with different sizes are visible on the bottom surface of the material. When the volume ratio is 1:1, 1:3 and 1:5, the sponge-like porous structure has compact and uniform pores, soft texture and good elasticity. 5% of bletilla striata gum liquid: the optimal ratio of the liquid volume ratio of the 4% carboxymethyl chitosan glue is 1: 3.
Example 2
A preparation method of a traditional Chinese medicine silver titanate composite porous material for healing burn wounds comprises the following steps:
preparing a silver titanate material by a hydrothermal method and an ultraviolet light photo-deposition method: dropwise adding 0.6ml of hydrofluoric acid (national drug group chemical reagent Co., Ltd.) with the concentration of 40% into 5ml of tetrabutyl titanate (national drug group chemical reagent Co., Ltd.), processing in a hydrothermal reaction kettle at 180 ℃ for 36h, adding silver nitrate with the mass of 1.0% of the intermediate into the intermediate, carrying out ultraviolet light deposition for 30min, and freeze-drying the final product at-20 ℃ under the pressure of 1.0mBar for 12h to obtain the silver titanate.
Mixing 10mL of 100mg/mL baicalin solution, 10mL of 5% rhizoma bletilla gelatin solution and 30mL of 4% carboxymethyl chitosan gelatin solution, placing in 55 deg.C water bath for 30min, fully crosslinking, and stirring until no bubble exists. And dropping the mixed gel liquid after the crosslinking reaction into a 24-hole plate, adding 0.6mL of liquid into each hole, cooling to room temperature, and adding 0.5mg of silver titanate powder.
And pre-freezing the mixed glue solution of the 24-pore plate containing the silver titanate in a refrigerator at the temperature of-20 ℃ for 24 hours. Then placing the mixture in a vacuum freeze dryer, and freeze-drying the mixture for 12 hours at the temperature of minus 20 ℃ and under the pressure of 1.0 mBar. The loading amount of the silver titanate is 1 wt%, and the traditional Chinese medicine silver titanate composite porous material for healing the burn wound is obtained.
Example 3
Morphology observation of traditional Chinese medicine silver titanate composite porous material for burn wound healing
The traditional Chinese medicine silver titanate composite porous material for healing of burn wounds, which is prepared in the embodiment 2, is placed on a sample plate adhered with a double-sided adhesive tape, and after gold plating, observation is performed under a scanning electron microscope to obtain a morphological diagram of the traditional Chinese medicine silver titanate composite porous material for healing of burn wounds. As shown in fig. 2, 3 and 4, fig. 2 is a scanning electron microscope (SEM 200X) of the traditional Chinese medicine silver titanate composite porous material for healing of burn wounds prepared in example 2, fig. 3 is a scanning electron microscope (SEM 1000X) of the traditional Chinese medicine silver titanate composite porous material for healing of burn wounds prepared in example 2, and fig. 4 is a scanning electron microscope (SEM 3000X) of the traditional Chinese medicine silver titanate composite porous material for healing of burn wounds prepared in example 2.
Example 4
Skin irritation test of traditional Chinese medicine silver titanate composite porous material
20 SD rats, half male and female, with body mass 180 + -20 g, provided by animal experiment center in Changhai hospital. License for use of experimental animal: SYXK (Shanghai) 2015-0017.
Rats were randomly divided into 2 groups of 10 rats each, a damaged skin group and a normal skin group. After the back of the rat is depilated for 24h, the broken skin group is marked with a # shape (only the stratum corneum is damaged, the subcutaneous tissue is not damaged) on the depilated area by using a sterile needle, and the degree is determined by the skin bleeding. The traditional Chinese medicine silver titanate composite porous material prepared in the embodiment 2 is pasted on damaged skin and covered and fixed by sterile gauze; the rats in the normal skin group are pasted on normal skin by using a traditional Chinese medicine silver titanate composite porous material and are covered and fixed by using sterile gauze. The skin contact part is observed at four time points of 1h, 24h, 48h and 72h, and the skin irritation signs such as erythema, edema and the like exist.
As shown in fig. 5, fig. 5 is a graph of the skin irritation test result of the traditional Chinese medicine silver titanate composite porous material for healing of burn wounds prepared in example 2 on the damaged skin group. As can be seen from the figure, the damaged skin of the rat with the damaged skin group, which is pasted with the traditional Chinese medicine silver titanate composite porous material on the back, has no adverse reactions such as erythema, edema and the like at all time points, and has no difference with the contrast of the pasted skin.
As shown in fig. 6, fig. 6 is a graph of the skin irritation test result of the traditional Chinese medicine silver titanate composite porous material for healing of burn wounds prepared in example 2 on a normal skin group. As can be seen from the figure, the skin of the rat with the normal skin group, which is pasted with the traditional Chinese medicine silver titanate composite porous material on the back, has no adverse reactions such as erythema, edema and the like at all time points, and has no difference with the contrast of the skin which is not pasted.
Example 5
Traditional Chinese medicine silver titanate composite porous material with effect of healing burn wound
SD rats 20 in half of male and female, weight 180 + -20 g, provided by animal experiment center in Changhai hospital. License for use of experimental animal: SYXK (Shanghai) 2015-0017.
The back of the rat is depilated before molding. Performing intraperitoneal injection anesthesia with 2% sodium pentobarbital according to the weight of 0.2mL/100g, fixing in prone position, rapidly taking out a self-made cylindrical copper iron (the bottom surface diameter is 14mm) which is heated in a constant temperature water bath kettle at 100 ℃ for 30min from the water bath kettle, and making the wound surface by contacting the skin under the action of self gravity for 8 seconds without applying pressure. And after each wound is finished, putting the wound back to the constant-temperature water bath kettle again to heat for 5 min. And (4) moving out of the SPF clean-grade animal experiment center after molding, and raising in a single cage in a common environment. After 24h of modeling, 1 rat was sacrificed at random, the burned wound tissue and normal skin tissue were taken, fixed in formalin, sectioned with paraffin, stained with HE, and examined for histological changes under a microscope, which was confirmed to be deep second degree burn.
The other 19 rats are subjected to self random control study, and 3 wound surfaces of each rat are randomly divided into 3 groups and marked, and the groups are divided into a normal saline group, a sulfadiazine silver group and a traditional Chinese medicine silver titanate composite porous material group. After molding for 1 day, corresponding drugs are respectively externally applied according to groups, and the wound surface is changed for 1 time every day.
Measuring the major diameter and the minor diameter of each wound by using a vernier caliper respectively 1 day after molding (before intervention) and 1, 3 and 7 days after intervention, and calculating the area of the wound and the healing rate of the wound, wherein the days for complete epithelialization of the wound is the healing time of the wound (the data is shown in table 2).
The area of the wound surface is 1/4 pi multiplied by the long diameter multiplied by the short diameter;
the wound healing rate is (area of wound before intervention-area of non-healed wound at each time point)/area of wound before intervention x 100%
As shown in fig. 7, fig. 7 is a statistical result chart of wound healing rates of the traditional Chinese medicine silver titanate composite porous material for burn wound healing prepared in example 1, and after 1 day of intervention, the healing rates of four groups have no statistical difference (P > 0.05); after 3 days and 7 days of intervention, the healing rate of the traditional Chinese medicine silver titanate composite porous material group is obviously superior to that of the normal saline group and the sulfadiazine silver group at the same time point, and the traditional Chinese medicine silver titanate composite porous material group has statistical significance (P is less than 0.05).
TABLE 2 wound healing Rate (%)
Figure BDA0001694556070000081
Group of After 1d intervention After intervention 3d After 7d intervention
Physiological saline group 3.57±8.74 12.92±12.26 35.34±12.75
Silver sulfadiazine 3.05±9.18 10.57±8.52 28.34±16.02
Traditional Chinese medicine silver titanate composite porous material group 10.42±10.18 29.70±14.71* 43.47±11.56*
The healing rate of the traditional Chinese medicine silver titanate composite porous material group is obviously higher than that of a normal saline group and a sulfadiazine silver group (P is less than 0.05) at the same time point.
The foregoing shows and describes the general principles, essential features, and advantages of the invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are given by way of illustration of the principles of the present invention, and that various changes and modifications may be made without departing from the spirit and scope of the invention as defined by the appended claims. The scope of the invention is defined by the appended claims and equivalents thereof.

Claims (11)

1. A traditional Chinese medicine silver titanate composite porous material for healing burn wounds is characterized in that: the composition is prepared from a baicalin solution, a bletilla striata gum solution and a carboxymethyl chitosan gum solution in a volume ratio of 1:1 (1-5), wherein: the concentration of the baicalin solution is 100mg/mL, the concentration of the bletilla gum solution is 5%, and the concentration of the carboxymethyl chitosan gum solution is 4%; the loading amount of the silver titanate is 0.1-5 wt%.
2. The traditional Chinese medicine silver titanate composite porous material for burn wound healing according to claim 1, characterized in that: the traditional Chinese medicine silver titanate composite porous material for healing the burn wound surface is prepared from a baicalin solution, a bletilla rubber cement solution and a carboxymethyl chitosan rubber cement solution in a volume ratio of 1:1: 3.
3. The traditional Chinese medicine silver titanate composite porous material for burn wound healing according to claim 1, characterized in that: the loading of the silver titanate is 1 wt%.
4. A method for preparing the traditional Chinese medicine silver titanate composite porous material for healing burn wounds, which is characterized by comprising the following steps of: the method comprises the following steps: mixing the baicalin solution, the bletilla striata gum solution and the carboxymethyl chitosan gum according to the proportion, reacting for 0.1-2 h at the temperature of 40-85 ℃, fully crosslinking until no bubbles exist, dripping the mixed gum solution into a 24-pore plate, adding 0.6mL of liquid into each pore, cooling to room temperature, and then adding silver titanate, wherein the concentration of the silver titanate in the 24-pore plate is 0.8-0.9 mg/mL; pre-freezing the 24-pore plate, and then carrying out vacuum freeze drying to obtain the traditional Chinese medicine silver titanate composite porous material for healing the burn wound.
5. The preparation method of the traditional Chinese medicine silver titanate composite porous material for healing burn wounds according to claim 4, characterized by comprising the following steps: the concentration of the silver titanate in the 24-hole plate is 0.83 mg/mL;
the preparation method of the silver titanate comprises the following steps: mixing tetrabutyl titanate with the volume ratio of 8-9: 1 and hydrofluoric acid with the concentration of 40%, carrying out hydrothermal treatment at 160-200 ℃ for 1-48 h, then adding silver nitrate with the mass of 0.5-1% of the intermediate into the intermediate, carrying out ultraviolet light photo-deposition for 1-60 min, and carrying out vacuum freeze drying, wherein the vacuum freeze drying is carried out for 12h under the conditions of-20 ℃ and the pressure of 1.0mBar, so as to obtain the silver titanate.
6. The preparation method of the traditional Chinese medicine silver titanate composite porous material for healing of burn wounds according to claim 5, characterized in that: the volume ratio of the tetrabutyl titanate to the hydrofluoric acid with the concentration of 40 percent is 50/6.
7. The preparation method of the traditional Chinese medicine silver titanate composite porous material for healing burn wounds according to claim 4, characterized by comprising the following steps: the pre-freezing temperature is-10 to-30 ℃, and the time is 1 to 48 hours.
8. The preparation method of the traditional Chinese medicine silver titanate composite porous material for healing of burn wounds according to claim 7, characterized in that: the pre-freezing temperature is-20 ℃ and the time is 24 h.
9. The preparation method of the traditional Chinese medicine silver titanate composite porous material for healing burn wounds according to claim 4, characterized by comprising the following steps: the vacuum freeze-drying conditions are as follows: the temperature is-10 to-40 ℃, the pressure is 0.07 to 1.0mBar, and the time is 1 to 48 hours.
10. The preparation method of the traditional Chinese medicine silver titanate composite porous material for healing burn wounds according to claim 9, characterized in that: the vacuum freeze-drying conditions are as follows: the temperature is-20 ℃, the pressure is 1.0mBar, and the time is 12 h.
11. Use of the traditional Chinese medicine silver titanate composite porous material for healing of burn wounds as claimed in any one of claims 1 to 3 in the preparation of a burn wound healing medicament.
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