CN113975191B - Composite cold compress patch and preparation method thereof - Google Patents

Composite cold compress patch and preparation method thereof Download PDF

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CN113975191B
CN113975191B CN202111265375.7A CN202111265375A CN113975191B CN 113975191 B CN113975191 B CN 113975191B CN 202111265375 A CN202111265375 A CN 202111265375A CN 113975191 B CN113975191 B CN 113975191B
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collagen
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CN113975191A (en
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苗盈
陈国靖
黄勇学
林睿禹
林雍球
陈武卿
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Shanghai Hengshi Medical Technology Co ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A61K8/735—Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F7/00—Heating or cooling appliances for medical or therapeutic treatment of the human body
    • A61F7/02—Compresses or poultices for effecting heating or cooling
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/24—Phosphorous; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F7/00—Heating or cooling appliances for medical or therapeutic treatment of the human body
    • A61F7/02—Compresses or poultices for effecting heating or cooling
    • A61F2007/0261—Compresses or poultices for effecting heating or cooling medicated
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/91—Injection

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Abstract

The invention provides a medical beauty treatment method for facial multi-point injection, belonging to the technical field of medical beauty treatment. The method comprises the following steps: (1) Mixing hydroxyapatite liquid, lidocaine liquid, sterilized water and hyaluronic acid uniformly to obtain filler; (2) Sterilizing the injection blunt needle for beauty treatment, and injecting the filling agent prepared in the step (1) into the needle tube; (3) selecting 7 symmetrical points of the left and right faces by the overall part: 2 sites on the anterior and medial sides of the arch, the lateral eyebrow, the lateral cheekbone, the pyriform fossa, the chin and the cheek, and carrying out disinfection treatment; (4) 2 sites on the anterior inner side of cheek and the arch position, the lateral eyebrow position, the lateral cheekbone position are injected by a blunt needle with the diameter of 25 mm; the injection was performed separately with a blunt needle 23mm in diameter under the chin muscle at the piriform fossa and chin. The face blunt needle injection is used for replacing the operation skin pulling or line carving, so that the large and irreversible wound surface of the operation is made up, the postoperative infection risk of line carving pulling and lifting is avoided, the safety coefficient is improved, and the performance is more stable.

Description

Composite cold compress patch and preparation method thereof
Technical Field
The invention relates to the technical field of beauty treatment and medical treatment, in particular to a composite cold compress patch and a preparation method thereof.
Background
Facial aging involves simultaneous changes in the skeleton, subcutaneous tissue, muscle, skin, and fixed ligaments, which can lead to skin atrophy, sagging, wrinkles, and fat displacement. During aging, the epidermis and deep subcutaneous tissue, fascia layers, bones, each layer should be adapted to its own reduced strength, reduced volume, reduced elasticity, resulting in dishing of tissue, sagging skin, pigmentation. However, facial fillers can correct facial aging-related indications and loss of tissue volume in a non-surgical manner and can produce long lasting optimal results with reduced invasiveness and recovery period.
At present, the filling of a single Hyaluronic Acid (HA) material is mainly pursued in the market, but the filling effect is only achieved in a short period, or the filling supporting effect can be achieved only after injection for a period of time, and the injection effect is not obvious after the material is metabolized. The reduced volume, elasticity and reduced support force of the various layers during facial aging can facilitate displacement of the filling material. Three types of facial injectable materials approved by the Chinese food and drug administration since month 2021 have increased filling materials with calcium hydroxyapatite (CaHA) and poly-L-lactic acid (PLLA) as main components. The novel material has the characteristic of stimulating the growth and biodegradation of the collagen. The post-filling effect needs to be exerted 1-3 months after injection, and the difference from the immediate filling effect of hyaluronic acid is obvious. And doctors with rich experience of injection of the novel materials are very rare. Therefore, the choice of materials for injection filling in the market is generally an option, and the defect of injection effect always exists.
In addition, sharp needle injection techniques are commonly used in the market, with a high risk of damage to the subcutaneous tissue and a risk of embolism. Facial aging is the result of multi-level aging, sharp needle injection can be performed only in a single subcutaneous layer, and the problem of improving facial aging in multiple dimensions cannot be achieved.
After performing a facial micro-plastic surgery, the face is often prone to inflammation and infection, and if there is no dressing to prevent inflammation, this would lead to serious post-operative reactions, affecting the patient's experience.
Disclosure of Invention
The invention aims to provide a composite cold compress patch and a preparation method thereof, wherein the face blunt needle injection is used for replacing the operation skin pulling or line carving, so that the large and irreversible wound surface of the operation is made up, the postoperative infection risk of the line carving pulling is avoided, the safety coefficient is improved, and the performance is more stable.
The technical scheme of the invention is realized as follows:
the invention provides a medical beauty treatment method by multi-point injection of a face, which comprises the following steps:
(1) Preparation of filler: mixing hydroxyapatite liquid, lidocaine liquid, sterilized water and hyaluronic acid uniformly to obtain filler;
(2) Preparation of a blunt needle: sterilizing the injection blunt needle for beauty treatment, and injecting the filling agent prepared in the step (1) into the needle tube;
(3) Selection of injection points: the whole face selects 14 injection points in total, namely 2 points of the arch position, the lateral cheekbone position, the pyriform fos position, the chin position and the front inner side of cheek of the left face and the right face which are symmetrical, and performs disinfection treatment;
(4) The injection method comprises the following steps: 2 sites on the anterior inner side of cheek and the arch position, the lateral eyebrow position, the lateral cheekbone position are injected by a blunt needle with the diameter of 25 mm; the patients received a total of 3-4.2mL of filler, after injection separately under the chin muscle at the piriform fossa, chin, with a blunt needle 23mm in diameter.
As a further improvement of the invention, the eyebrow arch position is the back eyebrow arch position; the side eyebrow position is at the tail of the eyebrow; the lateral cheekbone position is at the outer side under the eyes; the pyriform fossa is at the lower lacrimal duct; the chin is a tooth socket concave part; the anterior and medial 2 cheeks are at the lateral side of the apple muscle and at the nasal base, respectively.
As a further improvement of the present invention, the volume ratio of the hydroxyapatite liquid, the lidocaine liquid, the sterilized water and the hyaluronic acid is (1-2): (1-3): (1-2): (2-5), preferably 1:2:1:3.
As a further improvement of the present invention, the method further comprises the post-recovery processing step of: after injection, each position is coated with a compound cold compress with the area of 2cm multiplied by 2cm in time, and the compound cold compress is taken down after 15-25 min.
As a further improvement of the present invention, the method for preparing the composite cold compress comprises the steps of:
s1, extracting collagen: removing hair from fresh pigskin, removing subcutaneous fat, washing with clear water, cutting into pieces, degreasing with organic solvent, soaking and washing with acid solution with pH value of 1.5-2.5, adding pepsin for digestion, adjusting pH value to neutrality, salting out with NaCl of different concentrations, centrifuging, precipitating, purifying to obtain collagen, freeze drying, and preserving;
s2, glucose/SiO 2 /Fe 3 O 4 Preparation of porous nano-microspheres: adding sodium hexametaphosphate, ferrous chloride, a pore-forming agent and glucose into water, uniformly mixing, adding aminosilane, heating to 40-50 ℃, emulsifying, performing ultrasonic stirring reaction for 6-10h, filtering, and repeatedly washing the solid with water to obtain glucose/SiO 2 /Fe 3 O 4 Porous nano-microspheres;
S3.Ag/SiO 2 /Fe 3 O 4 preparation of porous nano-microspheres: glucose/SiO prepared in step S2 2 /Fe 3 O 4 Uniformly dispersing porous nanometer microsphere in water, dropwise adding silver ammonia solution while stirring, performing ultrasonic reaction for 1-3h, filtering, repeatedly washing solid with water, and drying to obtain Ag/SiO 2 /Fe 3 O 4 Porous nano-microspheres;
s4, ag/SiO loading 2 /Fe 3 O 4 Synthesis of PVP/PDA/collagen hydrogel of porous nanomicrospheres: dissolving the collagen freeze-dried product obtained in the step S1 in hydrochloric acid solution, regulating pH to 5.5-6.5, adding polyvinylpyrrolidone, heating to 35-45deg.C, stirring for 1-2 hr, regulating pH to 8-9, adding dopamine and Ag/SiO obtained in the step S3 2 /Fe 3 O 4 Stirring and mixing porous nanometer microsphere at room temperature for 20-30 hr, pouring into a mold, and drying at low temperature until water content is below 80% to obtain loaded Ag/SiO 2 /Fe 3 O 4 The PVP/PDA/collagen hydrogel of the porous nanometer microsphere is the composite cold compress patch.
As a further improvement of the invention, the organic solvent in the step S1 is a mixed solution of dichloromethane and ethanol, and the volume ratio is (5-10): 2; the acid liquor is a mixed aqueous solution of acetic acid and ethylenediamine tetraacetic acid, wherein the content of the acetic acid is 5-10wt% and the content of the ethylenediamine tetraacetic acid is 2-7wt%; the pepsin activity is 100-200U/mg, and the addition amount is 5-10wt% of the substrate; the soaking time is 4-5h.
As a further improvement of the present invention, the porogen in step S2 is selected from at least one of cetyl trimethylammonium bromide (CTAB), ethylene oxide-propylene oxide triblock copolymer PEO20-PPO70-PEO20 (P123), PEO106-PPO70-PEO106 (F127); the aminosilane is at least one selected from gamma-aminopropyl trimethoxysilane, gamma-aminopropyl triethoxysilane, N-beta (aminoethyl) -gamma-aminopropyl trimethoxysilane, N-beta (aminoethyl) -gamma-aminopropyl triethoxysilane, N-beta (aminoethyl) -gamma-aminopropyl methyl dimethoxy silane, N-beta (aminoethyl) -gamma-aminopropyl methyl diethoxy silane and diethylenetriamine propyl trimethoxysilane.
Preferably, the aminosilane is a compound mixture of gamma-aminopropyl trimethoxy silane and gamma-aminopropyl triethoxy silane, and the mass ratio is 3:1.
As a further improvement of the invention, the mass ratio of the sodium hexametaphosphate, ferrous chloride, the pore-forming agent, glucose and aminosilane in the step S2 is (1-3): (1-2): (0.1-0.5): (0.5-1): 10; and in the step S2, emulsifying for 1-2min under the condition that the emulsifying condition is 10000-20000r/min, the ultrasonic power is 500-1000W, and the stirring rotating speed is 300-500r/min.
As a further improvement of the present invention, the preparation method of the silver-ammonia solution in step S3 comprises: adding 1-3mol/L silver nitrate solution into a clean reaction container, dropwise adding 2-5mol/L ammonia water, and oscillating while dropwise adding until the initially generated precipitate is just completely dissolved to prepare silver-ammonia solution; the ultrasonic power is 500-1000W.
As a further improvement of the present invention, the collagen freeze-dried product, polyvinylpyrrolidone, dopamine and Ag/SiO in step S4 2 /Fe 3 O 4 The mass ratio of the porous nanometer microsphere is 10: (3-5): (2-4): (0.1-0.3); the low-temperature drying temperature is 20-35 ℃.
The invention has the following beneficial effects: the face blunt needle injection replaces the operation skin pulling or line carving, so that the large and irreversible wound surface of the operation is made up, the postoperative infection risk of the line carving pulling is avoided, the safety coefficient is improved, and the performance is more stable. The rheological properties of the calcium hydroxyapatite component (CaHAs) contribute to its precise localization in the bone resorption area, and the filling properties of Hyaluronic Acid (HA) contribute to the achievement of facial effects immediately after injection. The two components are matched to solve the problems of insufficient bone support, irregular contour amplification and sagging caused by pyriform fossa atrophy, cheekbone flattening and maxillary and mandibular atrophy, correct the indication related to facial aging and the loss of tissue volume through non-operative blunt needle facial injection, can generate immediate effect, can maintain lasting optimal result, reduce the invasiveness of sharp on tissues and reduce postoperative recovery period, and can be applied to comprehensively promoting the rejuvenation project.
Further, by applying the composite cold compress, the facial minimally invasive part can achieve the effects of diminishing inflammation, resisting and inhibiting bacteria, keeping the nutrients fully absorbed and even promoting the rapid recovery of the facial bottom layer.
glucose/SiO prepared by the invention 2 /Fe 3 O 4 In the porous nano microsphere, aminosilane is added into the solution, after emulsification, the aminosilane cannot be dissolved in water, after small liquid drops are formed, the amino part of the aminosilane is more prone to face outwards to the water phase, as the reaction proceeds, the amino group can be protonated to become amphiphilic molecules, the small liquid drops can be further stabilized, and meanwhile, the amino group protonation provides alkaline conditions, so that the SiO is generated by catalyzing the hydrolysis of the silane 2 Meanwhile, catalyzing sodium hexametaphosphate and ferrous chloride to generate Fe under alkaline condition 3 O 4 And with SiO 2 The shell layers of the nanospheres are mixed together to form a porous hollow sphere structure under the action of the pore-forming agent and the consumption of the internal reactants, and the hollow sphere shell layers are provided with a large number of hydroxyl groups which are easy to be subjected to hydrogen bond adsorption with glucose so as to obtain glucose/SiO 2 /Fe 3 O 4 The porous nanometer microsphere is further reacted with silver ammonia solution to produce Ag simple substance by surface glucose reduction reaction, thereby obtaining Ag/SiO 2 /Fe 3 O 4 Porous nano-microspheres;
grafting PVP and collagen under acidic condition to obtain copolymer, and addingPolymerizing dopamine under alkaline condition to obtain PVP/PDA/collagen hydrogel, and simultaneously adding Ag/SiO 2 /Fe 3 O 4 Porous nano microsphere, because the hydroxyl, carboxyl and amino groups on the polymer chain are easy to be combined with Ag/SiO 2 /Fe 3 O 4 Hydroxyl groups on the porous nano microspheres generate hydrogen bonds and electrostatic adsorption, so that the Ag/SiO loaded nano-porous nano microsphere is obtained 2 /Fe 3 O 4 The PVP/PDA/collagen hydrogel of the porous nanometer microsphere is put into a mould and dried to obtain the composite cold compress patch, and the composite cold compress patch has the advantages of excellent biocompatibility, good wound repair capability and anti-inflammatory effect, stable structure, promotion of cell proliferation, contribution to tissue healing and neovascularization, high safety, low immunogenicity, acceleration of wound healing, improvement of wound scar and pigmentation and the like, and meanwhile, the collagen, polyvinylpyrrolidone and polydopamine are chemically crosslinked, so that the activity of collagen peptide chains is restrained, and the mechanical property and the thermal stability of the material are obviously improved; meanwhile, the polydopamine has good adhesive property and biocompatibility, can improve the adhesive property of cold compress on the face, is nontoxic and easy to degrade, is favorable for absorbing nutrient substances, and is added with Ag/SiO in the composite cold compress 2 /Fe 3 O 4 The porous nano-microsphere not only can improve the antibacterial performance, but also has a certain massage effect on facial muscles because of forming granular texture, and the porous structure is favorable for the polymer to penetrate through the microsphere, so that the compatibility of inorganic materials and the polymer is improved. Meanwhile, fe 3 O 4 The particles can be used for forming micro magnetic field, and has certain physiotherapy effect on facial muscle, and contains magnetic Fe 3 O 4 After the composite cold compress is used, the composite cold compress can be added into water, after the polymer is dissolved, the microsphere is separated by utilizing magnetism, and the microsphere can be reused after being washed and dried and added into a new polymer substrate, so that the cost of the material is reduced, and the application value is high.
Drawings
In order to more clearly illustrate the embodiments of 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 some embodiments of the invention, and that other drawings can be obtained according to these drawings without inventive faculty for a person skilled in the art.
FIG. 1 shows the Ag/SiO obtained in example 1 2 /Fe 3 O 4 SEM image of porous nanospheres;
FIG. 2 shows the Ag/SiO obtained in example 1 2 /Fe 3 O 4 TEM image of porous nanospheres;
FIG. 3 is a schematic view of injection points of half face in example 7;
FIG. 4 is a graph showing the comparison of facial improvement of patients before and after cosmetic treatment in example 7.
Detailed Description
The following description of the technical solutions in the embodiments of the present invention will be clear and complete, and it is obvious that the described embodiments are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Preparation example 1
The preparation example provides a preparation method of a composite cold compress, which comprises the following steps:
s1, extracting collagen: 1kg of fresh pigskin is dehaired, subcutaneous fat is removed, the pigskin is washed by clear water and then cut into pieces, the pigskin is degreased by an organic solvent, and the organic solvent is a mixed solution of dichloromethane and ethanol, and the volume ratio is 5:2, soaking for 4 hours with acid liquor with the pH value of 1.5, washing for 3 times, wherein the acid liquor is a mixed aqueous solution of acetic acid and ethylenediamine tetraacetic acid, the content of the acetic acid is 5wt%, the content of the ethylenediamine tetraacetic acid is 2wt%, adding pepsin with the enzyme activity of 100U/mg for digestion, the addition amount is 5wt% of a substrate, then adjusting the pH value to be neutral, salting out with NaCl with different concentrations, centrifuging, precipitating and purifying to obtain collagen, freeze-drying for storage;
S2, glucose/SiO 2 /Fe 3 O 4 Preparation of porous nano-microspheres: 1mol of sodium hexametaphosphate and 1mol of chloridizingAdding ferrous iron, 0.1mol of hexadecyl trimethyl ammonium bromide and 0.5mol of glucose into 500mL of water, uniformly mixing, adding 10mol of gamma-aminopropyl triethoxysilane, heating to 40 ℃, emulsifying 1min at 10000r/min, performing 500W ultrasonic treatment, reacting for 6h under 300r/min stirring, filtering, and repeatedly washing the solid with water to obtain glucose/SiO 2 /Fe 3 O 4 Porous nano-microspheres;
s3, preparing silver ammonia solution: adding 1mol/L silver nitrate solution into a clean reaction container, dropwise adding 2mol/L ammonia water, and oscillating while dropwise adding until the initially generated precipitate is just completely dissolved to prepare silver-ammonia solution;
S4.Ag/SiO 2 /Fe 3 O 4 preparation of porous nano-microspheres: glucose/SiO prepared in step S2 2 /Fe 3 O 4 Uniformly dispersing porous nanometer microsphere in water, dropwise adding silver ammonia solution under stirring, performing 500W ultrasonic reaction for 1 hr, filtering, repeatedly washing the solid with water, and drying to obtain Ag/SiO 2 /Fe 3 O 4 Porous nano-microspheres;
s5, ag/SiO loading 2 /Fe 3 O 4 Synthesis of PVP/PDA/collagen hydrogel of porous nanomicrospheres: dissolving 10g of the collagen freeze-dried product prepared in the step S1 in 100mL of hydrochloric acid solution, regulating the pH value to 5.5, adding 3g of polyvinylpyrrolidone, heating to 35 ℃, stirring for 1h, regulating the pH value to 8, and adding 2g of dopamine and 0.1g of Ag/SiO prepared in the step S4 2 /Fe 3 O 4 Stirring and mixing porous nanometer microsphere at room temperature for 20 hr, pouring into a mold, drying at 20deg.C until water content is 78%, and obtaining loaded Ag/SiO 2 /Fe 3 O 4 The PVP/PDA/collagen hydrogel of the porous nanometer microsphere is the composite cold compress patch. The application of the invention meets the medical application detection standard of YZB/Lu Qing 0009-2007.
Preparation example 2
The preparation example provides a preparation method of a composite cold compress, which comprises the following steps:
s1, extracting collagen: 1kg of fresh pigskin is dehaired, subcutaneous fat is removed, the pigskin is washed by clear water and then cut into pieces, the pigskin is degreased by an organic solvent, and the organic solvent is a mixed solution of dichloromethane and ethanol, and the volume ratio is 5:1, soaking for 5 hours with acid liquor with the pH value of 2.5, washing for 3 times, wherein the acid liquor is a mixed aqueous solution of acetic acid and ethylenediamine tetraacetic acid, the content of the acetic acid is 10wt%, the content of the ethylenediamine tetraacetic acid is 7wt%, adding pepsin with the enzyme activity of 200U/mg for digestion, the addition amount is 10wt% of a substrate, then adjusting the pH value to be neutral, salting out with NaCl with different concentrations, centrifuging, precipitating and purifying to obtain collagen, freeze-drying for storage;
s2, glucose/SiO 2 /Fe 3 O 4 Preparation of porous nano-microspheres: adding 3mol of sodium hexametaphosphate, 2mol of ferrous chloride, 0.5mol of hexadecyl trimethyl ammonium bromide and 1mol of glucose into 500mL of water, uniformly mixing, adding 10mol of N-beta (aminoethyl) -gamma-aminopropyl triethoxysilane, heating to 50 ℃, emulsifying for 2min at 20000r/min, performing 1000W ultrasonic treatment, reacting for 10h under 500r/min stirring, filtering, and repeatedly washing the solid with water to obtain glucose/SiO 2 /Fe 3 O 4 Porous nano-microspheres;
s3, preparing silver ammonia solution: adding 3mol/L silver nitrate solution into a clean reaction container, dropwise adding 5mol/L ammonia water, and oscillating while dropwise adding until the initially generated precipitate is just completely dissolved to prepare silver-ammonia solution;
S4.Ag/SiO 2 /Fe 3 O 4 preparation of porous nano-microspheres: glucose/SiO prepared in step S2 2 /Fe 3 O 4 Uniformly dispersing porous nanometer microsphere in water, dropwise adding silver ammonia solution under stirring, performing 1000W ultrasonic reaction for 3h, filtering, repeatedly washing solid with water, and drying to obtain Ag/SiO 2 /Fe 3 O 4 Porous nano-microspheres;
s5, ag/SiO loading 2 /Fe 3 O 4 Synthesis of PVP/PDA/collagen hydrogel of porous nanomicrospheres: dissolving 10g of the collagen freeze-dried product prepared in the step S1 in 100mL of hydrochloric acid solution, regulating the pH value to be 6.5, adding 5g of polyvinylpyrrolidone, heating to 45 ℃, stirring for 2 hours, regulating the pH value to be 9, and adding 4g of dopamine and 0.3g of Ag/SiO prepared in the step S4 2 /Fe 3 O 4 Porous nanometer microsphere, stirring and mixing at room temperaturePouring into a mould for drying at 35 ℃ until the water content is 79% to obtain the loaded Ag/SiO 2 /Fe 3 O 4 The PVP/PDA/collagen hydrogel of the porous nanometer microsphere is the composite cold compress patch. The application of the invention meets the medical application detection standard of YZB/Lu Qing 0009-2007.
Preparation example 3
The preparation example provides a preparation method of a composite cold compress, which comprises the following steps:
s1, extracting collagen: 1kg of fresh pigskin is dehaired, subcutaneous fat is removed, the pigskin is washed by clear water and then cut into pieces, the pigskin is degreased by an organic solvent, and the organic solvent is a mixed solution of dichloromethane and ethanol, and the volume ratio is 7:2, soaking for 4.5 hours with acid liquor with the pH value of 2, washing for 3 times, wherein the acid liquor is a mixed aqueous solution of acetic acid and ethylenediamine tetraacetic acid, the content of the acetic acid is 7wt%, the content of the ethylenediamine tetraacetic acid is 5wt%, adding pepsin with the enzyme activity of 150U/mg for digestion, the addition amount is 7wt% of a substrate, then adjusting the pH value to be neutral, salting out with NaCl with different concentrations, centrifuging, precipitating and purifying to obtain collagen, freeze-drying for storage;
s2, glucose/SiO 2 /Fe 3 O 4 Preparation of porous nano-microspheres: adding 2mol of sodium hexametaphosphate, 1.5mol of ferrous chloride, 0.3mol of ethylene oxide-propylene oxide triblock copolymer PEO20-PPO70-PEO20 and 0.7mol of glucose into 500mL of water, uniformly mixing, adding 10mol of aminosilane, wherein the aminosilane is a compound mixture of gamma-aminopropyl trimethoxysilane and gamma-aminopropyl triethoxysilane, the mass ratio is 3:1, heating to 45 ℃, emulsifying for 1.5min at a speed of 15000r/min, performing ultrasonic treatment at 700W, reacting for 8h under stirring at 400r/min, filtering, and repeatedly washing the solid with water to obtain glucose/SiO 2 /Fe 3 O 4 Porous nano-microspheres;
s3, preparing silver ammonia solution: adding 2mol/L silver nitrate solution into a clean reaction container, dropwise adding 3.5mol/L ammonia water, and oscillating while dropwise adding until the precipitate generated at first is just completely dissolved to prepare silver-ammonia solution;
S4.Ag/SiO 2 /Fe 3 O 4 preparation of porous nano-microspheres: glucose/SiO prepared in step S2 2 /Fe 3 O 4 Uniformly dispersing porous nanometer microsphere in water, dropwise adding silver ammonia solution under stirring, performing 700W ultrasonic reaction for 2h, filtering, repeatedly washing solid with water, and drying to obtain Ag/SiO 2 /Fe 3 O 4 Porous nano-microspheres;
s5, ag/SiO loading 2 /Fe 3 O 4 Synthesis of PVP/PDA/collagen hydrogel of porous nanomicrospheres: dissolving 10g of the collagen freeze-dried product prepared in the step S1 in 100mL of hydrochloric acid solution, regulating the pH value to be 6, adding 4g of polyvinylpyrrolidone, heating to 40 ℃, stirring for 1.5h, regulating the pH value to be 8.5, and adding 3g of dopamine and 0.2g of Ag/SiO prepared in the step S4 2 /Fe 3 O 4 Stirring and mixing porous nanometer microsphere at room temperature for 25h, pouring into a mold, drying at 27deg.C until water content is 79%, and obtaining loaded Ag/SiO 2 /Fe 3 O 4 The PVP/PDA/collagen hydrogel of the porous nanometer microsphere is the composite cold compress patch. The application of the invention meets the medical application detection standard of YZB/Lu Qing 0009-2007.
Preparation example 4
Compared with preparation example 3, the aminosilane is gamma-aminopropyl trimethoxysilane, and other conditions are not changed. The application of the invention meets the medical application detection standard of YZB/Lu Qing 0009-2007.
Preparation example 5
Compared with preparation example 3, the aminosilane was gamma-aminopropyl triethoxysilane, and the other conditions were not changed. The application of the invention meets the medical application detection standard of YZB/Lu Qing 0009-2007.
Comparative preparation example 1
In comparison with preparation example 3, no Ag was added and the other conditions were not changed.
S1, extracting collagen: 1kg of fresh pigskin is dehaired, subcutaneous fat is removed, the pigskin is washed by clear water and then cut into pieces, the pigskin is degreased by an organic solvent, and the organic solvent is a mixed solution of dichloromethane and ethanol, and the volume ratio is 7:2, soaking for 4.5 hours with acid liquor with the pH value of 2, washing for 3 times, wherein the acid liquor is a mixed aqueous solution of acetic acid and ethylenediamine tetraacetic acid, the content of the acetic acid is 7wt%, the content of the ethylenediamine tetraacetic acid is 5wt%, adding pepsin with the enzyme activity of 150U/mg for digestion, the addition amount is 7wt% of a substrate, then adjusting the pH value to be neutral, salting out with NaCl with different concentrations, centrifuging, precipitating and purifying to obtain collagen, freeze-drying for storage;
S2.SiO 2 /Fe 3 O 4 Preparation of porous nano-microspheres: adding 2mol of sodium hexametaphosphate, 1.5mol of ferrous chloride and 0.3mol of ethylene oxide-propylene oxide triblock copolymer PEO20-PPO70-PEO20 into 500mL of water, uniformly mixing, adding 10mol of aminosilane, wherein the aminosilane is a compound mixture of gamma-aminopropyl trimethoxysilane and gamma-aminopropyl triethoxysilane, the mass ratio is 3:1, heating to 45 ℃, emulsifying for 1.5min at 15000r/min, carrying out ultrasonic treatment at 150W, carrying out reaction for 8h under 400r/min stirring, filtering, and repeatedly washing the solid with water to obtain SiO 2 /Fe 3 O 4 Porous nano-microspheres;
s3, loading SiO 2 /Fe 3 O 4 Synthesis of PVP/PDA/collagen hydrogel of porous nanomicrospheres: dissolving 10g of the collagen freeze-dried product prepared in the step S1 in 100mL of hydrochloric acid solution, regulating the pH value to be 6, adding 4g of polyvinylpyrrolidone, heating to 40 ℃, stirring for 1.5h, regulating the pH value to be 8.5, and adding 3g of dopamine and 0.2g of SiO prepared in the step S2 2 /Fe 3 O 4 Stirring and mixing porous nanometer microsphere at room temperature for 25h, pouring into a mold, drying at 27deg.C until water content is 77%, and obtaining loaded SiO 2 /Fe 3 O 4 The PVP/PDA/collagen hydrogel of the porous nanometer microsphere is the composite cold compress patch.
Comparative preparation example 2
Compared with preparation example 3, no Fe was added 3 O 4 Other conditions were unchanged.
S1, extracting collagen: 1kg of fresh pigskin is dehaired, subcutaneous fat is removed, the pigskin is washed by clear water and then cut into pieces, the pigskin is degreased by an organic solvent, and the organic solvent is a mixed solution of dichloromethane and ethanol, and the volume ratio is 7:2, soaking for 4.5 hours with acid liquor with the pH value of 2, washing for 3 times, wherein the acid liquor is a mixed aqueous solution of acetic acid and ethylenediamine tetraacetic acid, the content of the acetic acid is 7wt%, the content of the ethylenediamine tetraacetic acid is 5wt%, adding pepsin with the enzyme activity of 150U/mg for digestion, the addition amount is 7wt% of a substrate, then adjusting the pH value to be neutral, salting out with NaCl with different concentrations, centrifuging, precipitating and purifying to obtain collagen, freeze-drying for storage;
s2, glucose/SiO 2 Preparation of porous nano-microspheres: adding 0.3mol of ethylene oxide-propylene oxide triblock copolymer PEO20-PPO70-PEO20 and 0.7mol of glucose into 500mL of water, uniformly mixing, adding 10mol of aminosilane, wherein the aminosilane is a compound mixture of gamma-aminopropyl trimethoxysilane and gamma-aminopropyl triethoxysilane, the mass ratio is 3:1, heating to 45 ℃, emulsifying for 1.5min at 15000r/min, performing ultrasonic treatment at 700W, reacting for 8h under 400r/min stirring, filtering, and repeatedly washing the solid with water to obtain glucose/SiO 2 Porous nano-microspheres;
S3, preparing silver ammonia solution: adding 2mol/L silver nitrate solution into a clean reaction container, dropwise adding 3.5mol/L ammonia water, and oscillating while dropwise adding until the precipitate generated at first is just completely dissolved to prepare silver-ammonia solution;
S4.Ag/SiO 2 preparation of porous nano-microspheres: glucose/SiO prepared in step S2 2 Uniformly dispersing porous nanometer microsphere in water, dropwise adding silver ammonia solution under stirring, performing 700W ultrasonic reaction for 2h, filtering, repeatedly washing solid with water, and drying to obtain Ag/SiO 2 Porous nano-microspheres;
s5, ag/SiO loading 2 Synthesis of PVP/PDA/collagen hydrogel of porous nanomicrospheres: dissolving 10g of the collagen freeze-dried product prepared in the step S1 in 100mL of hydrochloric acid solution, regulating the pH value to be 6, adding 4g of polyvinylpyrrolidone, heating to 40 ℃, stirring for 1.5h, regulating the pH value to be 8.5, and adding 3g of dopamine and 0.2g of Ag/SiO prepared in the step S4 2 /Fe 3 O 4 Stirring and mixing porous nanometer microsphere at room temperature for 25h, pouring into a mold, drying at 27deg.C until water content is 78%, and obtaining loaded Ag/SiO 2 The PVP/PDA/collagen hydrogel of the porous nanometer microsphere is the composite cold compress patch.
Comparative preparation example 3
In comparison with preparation 3, no aminosilane was added and the other conditions were unchanged.
S1, extracting collagen: 1kg of fresh pigskin is dehaired, subcutaneous fat is removed, the pigskin is washed by clear water and then cut into pieces, the pigskin is degreased by an organic solvent, and the organic solvent is a mixed solution of dichloromethane and ethanol, and the volume ratio is 7:2, soaking for 4.5 hours with acid liquor with the pH value of 2, washing for 3 times, wherein the acid liquor is a mixed aqueous solution of acetic acid and ethylenediamine tetraacetic acid, the content of the acetic acid is 7wt%, the content of the ethylenediamine tetraacetic acid is 5wt%, adding pepsin with the enzyme activity of 150U/mg for digestion, the addition amount is 7wt% of a substrate, then adjusting the pH value to be neutral, salting out with NaCl with different concentrations, centrifuging, precipitating and purifying to obtain collagen, freeze-drying for storage;
s2, adding 2mol of sodium hexametaphosphate, 1.5mol of ferrous chloride, 0.3mol of ethylene oxide-propylene oxide triblock copolymer PEO20-PPO70-PEO20 and 0.7mol of glucose into 500mL of water, uniformly mixing, heating to 45 ℃, emulsifying for 1.5min at 15000r/min, carrying out ultrasonic treatment at 700W, and reacting for 8h under 400r/min stirring, wherein a microsphere structure is not formed, and subsequent reaction is not needed.
Comparative preparation example 4
In comparison with preparation 3, no dopamine was added and the other conditions were unchanged.
S1, extracting collagen: 1kg of fresh pigskin is dehaired, subcutaneous fat is removed, the pigskin is washed by clear water and then cut into pieces, the pigskin is degreased by an organic solvent, and the organic solvent is a mixed solution of dichloromethane and ethanol, and the volume ratio is 7:2, soaking for 4.5 hours with acid liquor with the pH value of 2, washing for 3 times, wherein the acid liquor is a mixed aqueous solution of acetic acid and ethylenediamine tetraacetic acid, the content of the acetic acid is 7wt%, the content of the ethylenediamine tetraacetic acid is 5wt%, adding pepsin with the enzyme activity of 150U/mg for digestion, the addition amount is 7wt% of a substrate, then adjusting the pH value to be neutral, salting out with NaCl with different concentrations, centrifuging, precipitating and purifying to obtain collagen, freeze-drying for storage;
S2, glucose/SiO 2 /Fe 3 O 4 Preparation of porous nano-microspheres: adding 2mol of sodium hexametaphosphate, 1.5mol of ferrous chloride, 0.3mol of ethylene oxide-propylene oxide triblock copolymer PEO20-PPO70-PEO20 and 0.7mol of glucose into 500mL of water, uniformly mixing, and adding 10mol of aminosilane, wherein the aminosilane is gamma-aminopropyl trimethoxysilane or gamma-aminopropyl triethoxy silaneThe compound mixture of the silane is heated to 45 ℃ in a mass ratio of 3:1, emulsified for 1.5min at a rotating speed of 15000r/min, subjected to 700W ultrasonic treatment, stirred for reaction for 8h at 400r/min, filtered, and the solid is repeatedly washed with water to obtain glucose/SiO 2 /Fe 3 O 4 Porous nano-microspheres;
s3, preparing silver ammonia solution: adding 2mol/L silver nitrate solution into a clean reaction container, dropwise adding 3.5mol/L ammonia water, and oscillating while dropwise adding until the precipitate generated at first is just completely dissolved to prepare silver-ammonia solution;
S4.Ag/SiO 2 /Fe 3 O 4 preparation of porous nano-microspheres: glucose/SiO prepared in step S2 2 /Fe 3 O 4 Uniformly dispersing porous nanometer microsphere in water, dropwise adding silver ammonia solution under stirring, performing 700W ultrasonic reaction for 2h, filtering, repeatedly washing solid with water, and drying to obtain Ag/SiO 2 /Fe 3 O 4 Porous nano-microspheres;
s5, ag/SiO loading 2 /Fe 3 O 4 Synthesis of PVP/PDA/collagen hydrogel of porous nanomicrospheres: dissolving 10g of the collagen freeze-dried product prepared in the step S1 in 100mL of hydrochloric acid solution, regulating the pH value to be 6, adding 7g of polyvinylpyrrolidone, heating to 40 ℃, stirring for 1.5h, regulating the pH value to be 8.5, and adding 0.2g of Ag/SiO prepared in the step S4 2 /Fe 3 O 4 Stirring and mixing porous nanometer microsphere at room temperature for 25h, pouring into a mold, drying at 27deg.C until water content is 77%, and obtaining loaded Ag/SiO 2 /Fe 3 O 4 The PVP/PDA/collagen hydrogel of the porous nanometer microsphere is the composite cold compress patch.
Comparative preparation example 5
In comparison with preparation 3, no polyvinylpyrrolidone was added, and the other conditions were not changed.
S1, extracting collagen: 1kg of fresh pigskin is dehaired, subcutaneous fat is removed, the pigskin is washed by clear water and then cut into pieces, the pigskin is degreased by an organic solvent, and the organic solvent is a mixed solution of dichloromethane and ethanol, and the volume ratio is 7:2, soaking for 4.5 hours with acid liquor with the pH value of 2, washing for 3 times, wherein the acid liquor is a mixed aqueous solution of acetic acid and ethylenediamine tetraacetic acid, the content of the acetic acid is 7wt%, the content of the ethylenediamine tetraacetic acid is 5wt%, adding pepsin with the enzyme activity of 150U/mg for digestion, the addition amount is 7wt% of a substrate, then adjusting the pH value to be neutral, salting out with NaCl with different concentrations, centrifuging, precipitating and purifying to obtain collagen, freeze-drying for storage;
s2, glucose/SiO 2 /Fe 3 O 4 Preparation of porous nano-microspheres: adding 2mol of sodium hexametaphosphate, 1.5mol of ferrous chloride, 0.3mol of ethylene oxide-propylene oxide triblock copolymer PEO20-PPO70-PEO20 and 0.7mol of glucose into 500mL of water, uniformly mixing, adding 10mol of aminosilane, wherein the aminosilane is a compound mixture of gamma-aminopropyl trimethoxysilane and gamma-aminopropyl triethoxysilane, the mass ratio is 3:1, heating to 45 ℃, emulsifying for 1.5min at a speed of 15000r/min, performing ultrasonic treatment at 700W, reacting for 8h under stirring at 400r/min, filtering, and repeatedly washing the solid with water to obtain glucose/SiO 2 /Fe 3 O 4 Porous nano-microspheres;
s3, preparing silver ammonia solution: adding 2mol/L silver nitrate solution into a clean reaction container, dropwise adding 3.5mol/L ammonia water, and oscillating while dropwise adding until the precipitate generated at first is just completely dissolved to prepare silver-ammonia solution;
S4.Ag/SiO 2 /Fe 3 O 4 preparation of porous nano-microspheres: glucose/SiO prepared in step S2 2 /Fe 3 O 4 Uniformly dispersing porous nanometer microsphere in water, dropwise adding silver ammonia solution under stirring, performing 700W ultrasonic reaction for 2h, filtering, repeatedly washing solid with water, and drying to obtain Ag/SiO 2 /Fe 3 O 4 Porous nano-microspheres;
s5, ag/SiO loading 2 /Fe 3 O 4 Synthesis of PVP/PDA/collagen hydrogel of porous nanomicrospheres: 10g of the collagen freeze-dried product prepared in the step S1 is dissolved in 100mL of ammonia water solution, the pH value is regulated to 8.5, 7g of dopamine and 0.2g of Ag/SiO prepared in the step S4 are added 2 /Fe 3 O 4 Stirring and mixing porous nanometer microsphere at room temperature for 25h, pouring into a mold, drying at 27deg.C until water content is 75%, and obtaining loaded Ag/SiO 2 /Fe 3 O 4 PVP of porous nano microsphereThe PDA/collagen hydrogel is the composite cold compress patch.
Comparative preparation example 6
In comparison with preparation example 3, no Ag/SiO was added 2 /Fe 3 O 4 The porous nanometer microsphere has unchanged other conditions.
S1, extracting collagen: 1kg of fresh pigskin is dehaired, subcutaneous fat is removed, the pigskin is washed by clear water and then cut into pieces, the pigskin is degreased by an organic solvent, and the organic solvent is a mixed solution of dichloromethane and ethanol, and the volume ratio is 7:2, soaking for 4.5 hours with acid liquor with the pH value of 2, washing for 3 times, wherein the acid liquor is a mixed aqueous solution of acetic acid and ethylenediamine tetraacetic acid, the content of the acetic acid is 7wt%, the content of the ethylenediamine tetraacetic acid is 5wt%, adding pepsin with the enzyme activity of 150U/mg for digestion, the addition amount is 7wt% of a substrate, then adjusting the pH value to be neutral, salting out with NaCl with different concentrations, centrifuging, precipitating and purifying to obtain collagen, freeze-drying for storage;
S2, synthesis of PVP/PDA/collagen hydrogel: dissolving 10g of the collagen freeze-dried product prepared in the step S1 in 100mL of hydrochloric acid solution, regulating the pH value to be 6, adding 4g of polyvinylpyrrolidone, heating to 40 ℃, stirring for 1.5h, regulating the pH value to be 8.5, adding 3g of dopamine, stirring and mixing for 25h at room temperature, pouring into a mould, drying at 27 ℃ until the water content is 79%, and obtaining PVP/PDA/collagen hydrogel, namely the composite cold compress patch.
Test example 1 antibacterial Property test
Taking 100 mu L of various bacterial suspensions with bacterial count turbidity of about 0.5Mcf, uniformly smearing the bacterial suspensions on the surface of a culture medium plate, shearing the composite cold compress prepared in examples 1-5, comparative examples 1-2 and comparative examples 4-6 into a round shape with the diameter of 6mm, taking round sterilizing filter paper sheets with the thickness of 3mm and the diameter of 6mm, immersing the filter paper sheets into physiological saline and penicillin for 30min, and then sticking the filter paper sheets on various bacterial-containing plates by using sterile forceps, wherein each plate is pasted with 6 filter paper sheets, and a certain distance is reserved between the filter paper sheets. All the above operations are performed on an ultra clean bench. Then, the culture was carried out at 37℃for 24 hours, and the diameter of the zone of inhibition of the round filter paper sheet was measured. The results are shown in Table 1.
TABLE 1
Figure GDA0004129495670000201
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As shown in the table above, the composite cold compress prepared by the invention has better antibacterial and bacteriostatic properties.
Test example 2 viscosity Performance test
The compound cold compress prepared in examples 1-5 and comparative examples 1-2, comparative examples 4-6 were tested for viscosity at 35℃respectively, and the results are shown in Table 2.
TABLE 2
Group of Viscosity (Pa, s)
Example 1 49
Example 2 48
Example 3 50
Example 4 48
Example 5 47
Comparative example 1 47
Comparative example 2 48
Comparative example 4 30
Comparative example 5 37
Comparative example 6 46
As shown in the table above, the composite cold compress prepared by the invention has better viscosity.
Test example 3 Performance test
The compound cold compress prepared in examples 1-5 and comparative examples 1-2, comparative examples 4-6 were tested for viscosity at 35℃respectively, and the results are shown in Table 3.
TABLE 3 Table 3
Group of pH(25℃) Tensile Strength (MPa) Peel strength (N/mm)
Standard of 5-7 ≥0.01 /
Example 1 6.7 0.021 1.0
Example 2 6.8 0.025 0.9
Example 3 6.9 0.027 1.2
Example 4 6.7 0.018 0.8
Example 5 6.8 0.017 0.7
Comparative example 1 6.7 0.016 0.8
Comparative example 2 6.8 0.017 0.8
Comparative example 4 6.5 0.012 0.4
Comparative example 5 6.6 0.011 0.7
Comparative example 6 6.7 0.015 0.9
As shown in the table above, the composite cold compress patch prepared by the invention has better comprehensive performance.
Test example 4 mouse test
10 healthy Kunming mice were anesthetized with pentobarbital (30 mg/kg), and the skin was excised entirely on one side of the back spine to form a circular overall skin excision wound surface with a diameter of 2cm, and the contralateral symmetrical skin was used as a normal self-control, and the composite cold patches prepared in examples 1 to 5 and comparative examples 1 to 2 and comparative examples 4 to 6 were applied to the wound surfaces of 7 healthy Kunming mice, respectively. The wound healing of each Kunming mouse on days 3, 10 and 15 after injury was observed, and the results are shown in Table 4.
TABLE 4 Table 4
Figure GDA0004129495670000231
Figure GDA0004129495670000241
As can be seen from Table 4, the composite cold compress of the present invention has an obvious effect of promoting healing of wound surfaces and the like.
Test example 5
1. Cytotoxicity of cells
The composite cold packs prepared in examples 1 to 5 and comparative examples 1 to 2 and comparative examples 4 to 6 were rated according to the United states pharmacopoeia. Cytotoxicity was no greater than grade I for all experimental groups.
2. Delayed hypersensitivity reaction
When the composite cold packs prepared in examples 1 to 5 and comparative examples 1 to 2 and comparative examples 4 to 6 were tested according to the method given in GB/T16886.10, all experimental groups had no delayed type hypersensitivity.
3. Intradermal stimulation
When the composite cold packs prepared in examples 1 to 5 and comparative examples 1 to 2 and comparative examples 4 to 6 were tested according to the method given in GB/T16886.10, the difference between the average scores of the test samples and the solvent controls of all the test groups was not more than 1.0.
Examples 4 and 5 compared with example 3, the use of aminosilane as the sole gamma-aminopropyl trimethoxysilane or gamma-aminopropyl triethoxysilane resulted in a less alkaline environment for catalyzing the sol gel reaction and Fe 3 O 4 Is affected by the formation of glucose/SiO formed 2 /Fe 3 O 4 Porous nano-microsphere has poor particle size, fe 3 O 4 The content is low, and part of the polymer is solid sphere, so that the polymer chain can not penetrate through the solid sphere when the polymer is added into the copolymer, the compatibility is poor, and the antibacterial and mechanical properties are affected to a certain extent. In comparative example 3, since no aminosilane was added, an alkaline environment could not be formed, and glucose/SiO was not obtained 2 /Fe 3 O 4 Porous nano-microspheres.
Comparative examples 1 and 2 did not contain Ag or Fe as produced in example 3 3 O 4 The antibacterial property and the wound healing property of the cold application are obviously reduced; comparative example 6 where Ag/SiO was not added 2 /Fe 3 O 4 The porous nanometer microsphere has obviously reduced antibacterial performance, wound healing performance and mechanical performance. This is because Ag has good antibacterial and bacteriostatic properties, and Ag/SiO are added 2 /Fe 3 O 4 The cold application of the porous nanometer microsphere can effectively inhibit bacteria, thereby preventing wound infection and improving wound healing effect.
Compared with the embodiment 3, the embodiment 4 and the embodiment 5 are respectively free from adding dopamine or polyvinylpyrrolidone, the viscosity and the peeling strength of the cold compress patch in the embodiment 4 are obviously reduced, and the polydopamine has good adhesion performance and biocompatibility, can improve the adhesion performance of the cold compress patch on the face, is nontoxic and easy to degrade, and is beneficial to the absorption of nutrient substances. The antibacterial property and the wound healing property of comparative example 5 are reduced, so that the polyvinylpyrrolidone has better effects of resisting bacteria, diminishing inflammation and promoting wound healing, and the addition of the polydopamine and the polyvinylpyrrolidone has a synergistic effect.
The hydroxyapatite solution was 35wt% hydroxyapatite, 2wt% carbomer (gel matrix), 3wt% glycerol (osmolality regulator) and 60wt% PBS buffer at pH 7.
The lidocaine solution was a 2wt% sterile aqueous solution of lidocaine.
Example 1
The embodiment provides a medical beauty treatment method for facial multi-point injection, which comprises the following steps:
(1) Preparation of filler: uniformly stirring and mixing 0.8mL of hydroxyapatite liquid, 0.8mL of lidocaine liquid, 0.8mL of sterilized water and 1.6mL of hyaluronic acid to obtain a filler;
(2) Preparation of a blunt needle: sterilizing the injection blunt needle for beauty treatment, and injecting the filling agent prepared in the step (1) into the needle tube;
(3) Selection of injection points: the whole face selects 14 injection points in total, namely 2 points of the arch position, the lateral cheekbone position, the pyriform fos position, the chin position and the front inner side of cheek of the left face and the right face which are symmetrical, and performs disinfection treatment;
(4) The injection method comprises the following steps: 2 sites on the anterior inner side of cheek and the arch position, the lateral eyebrow position, the lateral cheekbone position are injected by a blunt needle with the diameter of 25 mm; injection with a blunt needle 23mm in diameter under the chin muscle at the piriform fossa, chin, and finally, the patient received a total of 4mL of filler;
the eyebrow arch position is a back eyebrow arch position; the side eyebrow position is at the tail of the eyebrow; the lateral cheekbone position is at the outer side under the eyes; the pyriform fossa is at the lower lacrimal duct; the chin is a tooth socket concave part; the anterior and medial 2 cheeks are at the lateral side of the apple muscle and at the nasal base, respectively.
Example 2
The embodiment provides a medical beauty treatment method for facial multi-point injection, which comprises the following steps:
(1) Preparation of filler: uniformly stirring and mixing 0.5mL of hydroxyapatite liquid, 1mL of lidocaine liquid, 0.5mL of sterilized water and 1.5mL of hyaluronic acid to obtain a filler;
(2) Preparation of a blunt needle: sterilizing the injection blunt needle for beauty treatment, and injecting the filling agent prepared in the step (1) into the needle tube;
(3) Selection of injection points: the whole face selects 14 injection points in total, namely 2 points of the arch position, the lateral cheekbone position, the pyriform fos position, the chin position and the front inner side of cheek of the left face and the right face which are symmetrical, and performs disinfection treatment;
(4) The injection method comprises the following steps: 2 sites on the anterior inner side of cheek and the arch position, the lateral eyebrow position, the lateral cheekbone position are injected by a blunt needle with the diameter of 25 mm; injection with a blunt needle 23mm in diameter under the chin muscle at the piriform fossa, chin, and finally, the patient received a total of 3.5mL of filler;
the eyebrow arch position is a back eyebrow arch position; the side eyebrow position is at the tail of the eyebrow; the lateral cheekbone position is at the outer side under the eyes; the pyriform fossa is at the lower lacrimal duct; the chin is a tooth socket concave part; the anterior and medial 2 cheeks are at the lateral side of the apple muscle and at the nasal base, respectively.
Example 3
The embodiment provides a medical beauty treatment method for facial multi-point injection, which comprises the following steps:
(1) Preparation of filler: uniformly stirring and mixing 0.5mL of hydroxyapatite liquid, 1mL of lidocaine liquid, 0.5mL of sterilized water and 1.5mL of hyaluronic acid to obtain a filler;
(2) Preparation of a blunt needle: sterilizing the injection blunt needle for beauty treatment, and injecting the filling agent prepared in the step (1) into the needle tube;
(3) Selection of injection points: the whole face selects 14 injection points in total, namely 2 points of the arch position, the lateral cheekbone position, the pyriform fos position, the chin position and the front inner side of cheek of the left face and the right face which are symmetrical, and performs disinfection treatment; the eyebrow arch position is a back eyebrow arch position; the side eyebrow position is at the tail of the eyebrow; the lateral cheekbone position is at the outer side under the eyes; the pyriform fossa is at the lower lacrimal duct; the chin is a tooth socket concave part; the anterior and medial 2 cheeks are respectively at the lateral side of apple muscle and at the nasal base;
(4) The injection method comprises the following steps: 2 sites on the anterior inner side of cheek and the arch position, the lateral eyebrow position, the lateral cheekbone position are injected by a blunt needle with the diameter of 25 mm; injection with a blunt needle 23mm in diameter under the chin muscle at the piriform fossa, chin, and finally, the patient received a total of 3.5mL of filler;
(5) Post-treatment: after injection, each site is coated with the composite cold compress patch prepared in example 3 with the area of 2cm multiplied by 2cm in time, and the composite cold compress patch is taken down after 20 minutes of application.
Example 4
The embodiment provides a medical beauty treatment method for facial multi-point injection, which comprises the following steps:
(1) Preparation of filler: uniformly stirring and mixing 0.5mL of hydroxyapatite liquid, 1mL of lidocaine liquid, 0.5mL of sterilized water and 1.5mL of hyaluronic acid to obtain a filler;
(2) Preparation of a blunt needle: sterilizing the injection blunt needle for beauty treatment, and injecting the filling agent prepared in the step (1) into the needle tube;
(3) Selection of injection points: selecting 14 injection points in total of 7 symmetrical points of the whole face, referring to fig. 4, fig. 4 is a schematic diagram of injection points of a half face; the eyebrow arch position, the lateral eyebrow position, the lateral cheek bone position, the pyriform fossa position, the chin position and the anterior and medial cheek position which are symmetrical to the left and right faces are respectively treated with disinfection treatment; the eyebrow arch position is a back eyebrow arch position; the side eyebrow position is at the tail of the eyebrow; the lateral cheekbone position is at the outer side under the eyes; the pyriform fossa is at the lower lacrimal duct; the chin is a tooth socket concave part; the anterior and medial 2 cheeks are respectively at the lateral side of apple muscle and at the nasal base;
(4) The injection method comprises the following steps: 2 sites on the anterior inner side of cheek and the arch position, the lateral eyebrow position, the lateral cheekbone position are injected by a blunt needle with the diameter of 25 mm; injection with a blunt needle 23mm in diameter under the chin muscle at the piriform fossa, chin, and finally, the patient received a total of 3.5mL of filler;
(5) Post-treatment: after injection, each site is coated with the composite cold compress patch prepared in example 3 with the area of 2cm multiplied by 2cm in time, and the composite cold compress patch is taken down after 20 minutes of application.
FIG. 4 is a graph showing the effects of the face multi-point injection medical cosmetic method of the present embodiment before and after treatment, A is a front view before treatment; b is a treatment front side view; c is front irradiation after treatment; d is a side view after treatment. During cosmetic treatment, although global improvement is the goal, only eyebrow position and upper cheek fullness are graded, as there is no effective global assessment quantitative scale. The filler is placed on the upper plane of the arch bone of the patient, so that the arch bone can be lifted. The filling of the lateral eyebrows (brow tail), lateral cheeks (under-eye lateral side) and anterior medial cheek (apple muscle lateral side) lifts her eyebrows laterally while also lifting her middle of face and cheek while redefining cheek vertices. The filling lifts the pyriform fossa (the lower tear duct) and releases her nasolabial folds, while the chin filling improves her mental folds and supports her chin profile. The external canthus of the patient is obviously lifted, the front inner side of the cheek is protruded, and the chin is protruded more smoothly (the depth of the dimple is less). Immediately after injection, the eyebrows and lateral canthus are lifted and the anterior and medial cheek areas are more prominent. Although no serious adverse events were observed, all patients treated with this regimen had slight swelling, ecchymosis and erythema immediately after injection, without requiring further treatment, and symptoms disappeared within 1 day. 1 month after treatment, no long-term complications occur.
The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, alternatives, and improvements that fall within the spirit and scope of the invention.

Claims (7)

1. The preparation method of the composite cold compress is characterized by comprising the following steps of:
s1, extracting collagen: removing hair from fresh pigskin, removing subcutaneous fat, washing with clear water, cutting into pieces, degreasing with organic solvent, soaking and washing with acid solution with pH value of 1.5-2.5, adding pepsin for digestion, adjusting pH value to neutrality, salting out with NaCl of different concentrations, centrifuging, precipitating, purifying to obtain collagen, freeze drying, and preserving;
s2, glucose/SiO 2 /Fe 3 O 4 Preparation of porous nano-microspheres: adding sodium hexametaphosphate, ferrous chloride, a pore-forming agent and glucose into water, uniformly mixing, adding aminosilane, heating to 40-50 ℃, emulsifying, performing ultrasonic stirring reaction for 6-10h, filtering, and repeatedly washing the solid with water to obtain glucose/SiO 2 /Fe 3 O 4 Porous nano-microspheres;
S3.Ag/SiO 2 /Fe 3 O 4 preparation of porous nano-microspheres: glucose/SiO prepared in step S2 2 /Fe 3 O 4 Uniformly dispersing porous nanometer microsphere in water, dropwise adding silver ammonia solution while stirring, performing ultrasonic reaction for 1-3h, filtering, repeatedly washing solid with water, and drying to obtain Ag/SiO 2 /Fe 3 O 4 Porous nano-microspheres;
s4, ag/SiO loading 2 /Fe 3 O 4 Synthesis of PVP/PDA/collagen hydrogel of porous nanomicrospheres: dissolving the collagen freeze-dried product obtained in the step S1 in hydrochloric acid solution, regulating pH to 5.5-6.5, adding polyvinylpyrrolidone, heating to 35-45deg.C, stirring for 1-2 hr, regulating pH to 8-9, adding dopamine and Ag/SiO obtained in the step S3 2 /Fe 3 O 4 Stirring and mixing porous nanometer microsphere at room temperature for 20-30 hr, pouring into a mold, and drying at low temperature until water content is below 80% to obtain loaded Ag/SiO 2 /Fe 3 O 4 The PVP/PDA/collagen hydrogel of the porous nanometer microsphere is the composite cold compress patch.
2. The preparation method according to claim 1, wherein the organic solvent in step S1 is a mixed solution of dichloromethane and ethanol, and the volume ratio is (5-10): 2; the acid liquor is a mixed aqueous solution of acetic acid and ethylenediamine tetraacetic acid, wherein the content of the acetic acid is 5-10wt% and the content of the ethylenediamine tetraacetic acid is 2-7wt%; the pepsin activity is 100-200U/mg, and the addition amount is 5-10wt% of the substrate; the soaking time is 4-5h.
3. The method of claim 1, wherein the porogen in step S2 is selected from at least one of cetyltrimethylammonium bromide (CTAB), ethylene oxide-propylene oxide triblock copolymer PEO20-PPO70-PEO20 (P123), PEO106-PPO70-PEO106 (F127); the aminosilane is at least one selected from gamma-aminopropyl trimethoxysilane, gamma-aminopropyl triethoxysilane, N-beta (aminoethyl) -gamma-aminopropyl trimethoxysilane, N-beta (aminoethyl) -gamma-aminopropyl triethoxysilane, N-beta (aminoethyl) -gamma-aminopropyl methyl dimethoxy silane, N-beta (aminoethyl) -gamma-aminopropyl methyl diethoxy silane and diethylenetriamine propyl trimethoxysilane.
4. The method according to claim 1, wherein the mass ratio of sodium hexametaphosphate, ferrous chloride, pore-forming agent, glucose and aminosilane in step S2 is (1-3): (1-2): (0.1-0.5): (0.5-1): 10; the emulsifying condition is that the emulsifying is carried out for 1-2min at the rotating speed of 10000-20000r/min, the ultrasonic power is 500-1000W, and the stirring rotating speed is 300-500r/min.
5. The preparation method according to claim 1, wherein the preparation method of the silver-ammonia solution in step S3 comprises: adding 1-3mol/L silver nitrate solution into a clean reaction container, dropwise adding 2-5mol/L ammonia water, and oscillating while dropwise adding until the initially generated precipitate is just completely dissolved to prepare silver-ammonia solution; the ultrasonic power is 500-1000W.
6. The method according to claim 1, wherein the collagen freeze-dried product, polyvinylpyrrolidone, dopamine and Ag/SiO in step S4 2 /Fe 3 O 4 The mass ratio of the porous nanometer microsphere is 10: (3-5): (2-4): (0.1-0.3); the low-temperature drying temperature is 20-35 ℃.
7. A composite cold patch produced by the production method according to any one of claims 1 to 6.
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CN108434125A (en) * 2018-04-25 2018-08-24 福州大学 A kind of preparation method of mesoporous silicon oxide-insulin nano sustained release transdermal skin patches
CN110292653A (en) * 2019-07-09 2019-10-01 洛阳理工学院 A kind of Collagon base nanometer compound hemostatic material and preparation method thereof with bacteriostasis efficacy
CN111467483A (en) * 2020-04-17 2020-07-31 南京鼓楼医院 Preparation method and application of magnetic nano microcarrier wrapping tumor cell membrane
CN112315822A (en) * 2020-10-21 2021-02-05 杭州协合医疗用品有限公司 Diatom mineral mud mask and preparation method thereof

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108434125A (en) * 2018-04-25 2018-08-24 福州大学 A kind of preparation method of mesoporous silicon oxide-insulin nano sustained release transdermal skin patches
CN110292653A (en) * 2019-07-09 2019-10-01 洛阳理工学院 A kind of Collagon base nanometer compound hemostatic material and preparation method thereof with bacteriostasis efficacy
CN111467483A (en) * 2020-04-17 2020-07-31 南京鼓楼医院 Preparation method and application of magnetic nano microcarrier wrapping tumor cell membrane
CN112315822A (en) * 2020-10-21 2021-02-05 杭州协合医疗用品有限公司 Diatom mineral mud mask and preparation method thereof

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