CN115487172B - X-ray protective agent and preparation method thereof - Google Patents
X-ray protective agent and preparation method thereof Download PDFInfo
- Publication number
- CN115487172B CN115487172B CN202211299812.1A CN202211299812A CN115487172B CN 115487172 B CN115487172 B CN 115487172B CN 202211299812 A CN202211299812 A CN 202211299812A CN 115487172 B CN115487172 B CN 115487172B
- Authority
- CN
- China
- Prior art keywords
- protective agent
- ray
- ray protective
- phase
- metal compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/133—Amines having hydroxy groups, e.g. sphingosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/245—Bismuth; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/16—Emollients or protectives, e.g. against radiation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention discloses an X-ray protective agent, which comprises a base matrix, a metal compound, triethanolamine and the balance of deionized water, wherein the mass ratio of the base matrix in the X-ray protective agent is 8.5-18.6%, the mass ratio of the metal compound in the X-ray protective agent is 10-70%, the mass ratio of the triethanolamine in the X-ray protective agent is 0.2-1% and the balance of deionized water. The base matrix adopted by the protective agent contains triethanolamine, can form a synergistic effect with the metal compound, can prevent direct and indirect damage of X-rays to skin, and has a good effect on preventing radioactive skin inflammation caused by the X-rays. The application of the product comprises interventional operation, orthopedic operation, implantation radiotherapy operation, and the use of radiopharmaceuticals in nuclear medicine for the protection of medical staff; other applications are in the field of X-ray protection during radiological procedures.
Description
Technical Field
The invention belongs to the technical field of biological medicine, and particularly discloses application of an X-ray protective agent in X-ray or radionuclide imaging or treatment and a preparation method thereof.
Background
Interventional radiology (Interventional Radiology, IR) refers to a series of techniques for guiding, positioning, monitoring and recording in medical imaging devices, percutaneous puncture or insertion of a specially-made catheter or instrument through a natural orifice of the human body into a lesion site, and invasive diagnosis or minimally invasive treatment of various diseases. The interventional radiology diagnosis and treatment technology has been widely applied in clinical practice, and the interventional radiology technology has been rapidly developed in recent years due to the advantages of minimally invasive treatment, high accuracy, quicker postoperative recovery and the like, and the number of clinical cases of interventional radiology is increased. During the interventional diagnosis and treatment process, a doctor carries out the near-distance treatment on a patient through equipment such as a catheter under the assistance of an X-ray imaging machine, so that a worker operating at the bedside can receive higher radiation dose, and the hand can occasionally enter an irradiation field to be directly irradiated, so that the radiation dose received by clinical medical staff in the operation is far higher than that of radiation workers of other work types. The biological deterministic effects of radiation on bare skin range from erythema, dehairing to skin necrosis, and also can have deleterious effects on the human body, so its radioprotection safety has been the focus and hotspot of radioprotection research.
The hand is the nearest part of the human body to the radioactive source, and is sometimes directly exposed to the ray beam, and the dose detection data of the hand indicate that when a great deal of cardiac pacemaker implantation is performed, the annual equivalent dose of the hand of a doctor may exceed the annual limit of 500 mSv. In the existing operation process, professional wearing protective operation gloves in the interventional radiology procedure can effectively reduce the irradiated dose of hands, however, the existing protective operation gloves are mostly thicker lead rubber gloves, but because the interventional radiology operation is aseptic operation, double-layer wearing gloves are needed (the inner layer is the protective operation glove and the outer layer is the disposable latex glove), the sensitivity of the hands is reduced, and the operation of operators is affected, so the protective operation gloves are rarely applied in practice. Some novel materials are made and designed into protective gloves, lead is replaced by tungsten or bismuth and other materials, the texture is lighter and thinner, however, the manufacturing cost is higher, the disposable use cost is higher, and the protective gloves are not popularized clinically. At present, researchers try to make protective cream to protect the human body from the damage of X rays, and compared with thicker lead rubber gloves, the protective cream has more convenience and can not influence the operation in the operation. However, the existing product also has some technical difficulties, firstly, too much metal compound is added into the protective paste, which can cause the dispersion of the metal compound in the protective paste, so that the protective paste cannot be uniformly coated on the skin surface, and the protective effect is reduced, secondly, the fluidity of the cream is poor due to the increase of the addition of the metal compound, so that the cream is difficult to clean, and remains on the skin, so that heavy metals remain, and damage to the body is caused, and thirdly, the skin may be irritated, inflammation or allergy is caused due to the addition of the metal compound.
Therefore, the problem of hand protection measures of medical personnel in the interventional radiology process is needed to be solved. On the other hand, in the case of radionuclide therapy and diagnosis in the nuclear medicine, the preparation of radiopharmaceuticals and the risk of external irradiation of the surrounding population after the patient has received the radiopharmaceutical therapy, and thus, it is necessary to perform corresponding radioprotection of the partially exposed skin.
Disclosure of Invention
Aiming at the problems in the prior art, the invention discloses a novel X-ray protective agent, which not only can reduce the additive of metal compounds, but also can improve the capability of the protective agent for protecting the skin from direct and indirect damage caused by X-rays.
The invention is realized by the following technical scheme:
the invention provides an X-ray protective agent which comprises a base matrix, a metal compound, triethanolamine and the balance of deionized water, wherein the mass ratio of the base matrix in the X-ray protective agent is 8.5-18.6%, the mass ratio of the metal compound in the X-ray protective agent is 10-70%, the mass ratio of the triethanolamine in the X-ray protective agent is 0.2-1% and the balance of deionized water.
The design of the invention, the triethanolamine can relax local blood vessels of the skin and accelerate the blood flow speed, thereby improving the healing capacity of X-ray irradiated tissues; the triethanolamine is also matched with the metal compound and applied to the basic matrix, so that the X-ray can be prevented from directly and indirectly damaging the skin, and the radiation skin inflammation caused by the X-ray can be well treated; the basic matrix is favorable for uniform distribution of the metal compound on the skin, so that the protective effect of the X-ray protective agent is improved, and triethanolamine can be matched to slow down the irritation of the metal compound on the skin.
As a further proposal, the base matrix comprises A phase and B phase, wherein the mass ratio of A phase to B phase is (4.4-7.6): 4.1-11; wherein the phase A consists of hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer, acrylic acid (esters) type/C10-30 alkanol acrylate cross-linked polymer, glycerin and carbomer, the mass ratio of the hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer to the acrylic acid (esters) type/C10-30 alkanol acrylate cross-linked polymer to the glycerin to the carbomer is (0.1-0.5): (0.2-0.6): (4-6): (0.1-0.5); the phase B consists of methyl glucitol polyether, jojoba esters, squalane, mineral oil and ethylparaben, wherein the mass ratio of the methyl glucitol polyether to the jojoba esters to the squalane to the mineral oil to the ethylparaben is (0.5-1.5): 0.5-2): 2-4): 1-3: 0.1-0.5. The water content in the X-ray protective agent is low, and the intra-molecular hydrogen bond and electrostatic interaction of the hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer promote the intra-molecular hydrophobic association under the low concentration, so that the overall stability of the X-ray protective agent is improved; the use of hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer in combination with acrylic acid (esters) and C10-30 alkanol acrylate cross-linked polymer can lead the X-ray protective agent of the invention to have better rheological characteristics and excellent stability; the carbomer can not only enhance the resistance of the skin, but also has certain anti-inflammatory and bactericidal effects, although the triethanolamine can improve the healing capacity of radiotherapy tissues, eczema is easy to cause, so that skin pain, itching and the like are caused, the carbomer in the basic matrix can improve the skin problem caused by the triethanolamine, and the carbomer is matched with glycerol, so that the fusion of the carbomer and the skin surface can be promoted, and the resistance of the skin is improved. Methyl glucitol polyethers have moisturization and promote solubility; the jojoba esters can moisturize skin and increase oxidation resistance of skin; squalane can promote metabolism of cells and help repair damaged cells; the ethylparaben has antiseptic effect. As the X-ray is a process of releasing energy, the oxygen free radical level of local tissues can be increased, the jojoba esters can improve the oxidation resistance of the skin, and the damage of the X-ray to the skin is reduced; the squalane and the triethanolamine are matched with each other to promote the tissue treatment and the self-healing capacity of the tissue; although ethylparaben has an antiseptic effect, few people can generate allergic symptoms, and adverse reactions of ethylparaben can be eliminated by matching carbomer in the phase A in a basic matrix; whereas methyl glucitol polyether and mineral oil promote the intersolubility of the various materials in phase B.
The base matrix is divided into the phase A and the phase B, so as to improve the solubility of the two phases, so that the two phases can be well mixed uniformly, and the overall uniformity of the base matrix is improved. The glycerin in the A phase, the methyl glucitol polyether in the B phase and the mineral oil can promote the dissolution of substances in each phase and the fusion of substances in the phase, so that the mutual coordination of the substances in the phase is promoted. Not only can the uniformity of the basal matrix and the protection of the skin be improved; moreover, the uniformity of the dispersion of the metal compound and the triethanolamine in the base matrix can be further improved, so that the protection effect of the protective agent is improved.
As a further aspect, the metal compound includes one or more of barium sulfate, bismuth oxide, and a rare earth metal compound.
As a further scheme, the particle size of the metal compound is controlled to be 2 mu m-10nm. The particle size of the metal compound is very critical to the protective effect of the X-ray protective agent, and the excessive particle size of the metal compound powder can cause difficulty in uniformly dispersing in a basic matrix in the preparation process, and the finished product is difficult to uniformly coat on the surface of skin, so that the radiation protective effect is affected; too small a particle size of the metal compound may pass through the skin barrier, resulting in vivo residues of heavy metal elements. The particle size of the metal compound is controlled to be 2 mu m-10nm, so that the radiation protection effect can be ensured, and meanwhile, the metal compound has good biological safety.
As still further scheme, the particle size of the metal compound is controlled to be 400-600nm. Not only can ensure the protection effect of the protective agent, but also can reduce the addition amount of the metal compound in the protective agent, thereby reducing the expenditure of cost.
As a further scheme, the mass ratio of the base matrix in the X-ray protective agent is 10% -15% by mass; the mass ratio of the metal compound in the X-ray protective agent is 50% -70% and the mass ratio of the triethanolamine in the X-ray protective agent is 0.5% -1%.
The invention also provides a preparation method of the X-ray protective agent, which comprises the following steps: dissolving the phase A in water, heating, and stirring to uniformly disperse the phase A; adding the B phase and the triethanolamine into an oil pan for heating and dissolving, and stirring to uniformly disperse the B phase and the triethanolamine; pumping the phase A into an emulsifying pot, pumping the mixture of the phase B and triethanolamine into the oil pot under the condition of rapid stirring, emulsifying, homogenizing, preserving heat, stirring, cooling for the first time, adding a metal compound and deionized water to prepare a metal compound suspension, stirring uniformly, cooling for the second time, stirring uniformly, discharging, filling, packaging, sterilizing by irradiation, and warehousing after inspection is qualified.
As a further scheme, the temperature of the phase A dissolved in water and heated is 80-85 ℃; the temperature of the oil pan for heating and dissolving is 80-85 ℃; the time of emulsification and homogenization is 5-8 minutes, and the time of heat preservation and stirring is 25-30 minutes; the temperature is reduced to 60 ℃ for the first time; and cooling to 40 ℃ for the second time.
The X-ray protective agent can be prepared into various dosage forms, including one or more of ointment, cream, gel, liniment, patch, paste and film coating agent.
The invention also provides the application of the X-ray protective agent in preventing the radioactive damage of X-rays to a body.
As a further aspect, the injury comprises one or more of skin injury, digestive system injury, and/or protection from hematopoietic system injury; the source of X-ray comprises C-arm X-ray machine, digital X-ray photography system, mammary X-ray machine, X-ray generated by panoramic dental film machine medical imaging equipment, and radioactive particle iodine 125 Palladium (Pd) 103 Iridium (Iridium) 192 One or more of the X-rays are generated during particle implantation radiotherapy.
The invention has the characteristics and beneficial effects that:
(1) The main component of the X-ray protective agent is lead-free metal compound powder, has good biological safety, is environment-friendly in the production process, and does not cause environmental pollution.
(2) The base matrix adopted by the protective agent contains triethanolamine, can form a synergistic effect with metal compounds, can prevent direct and indirect damage of X-rays to skin, and has good treatment effect on preventing radioactive skin inflammation caused by the X-rays.
(3) The protective agent disclosed by the invention has the advantages that due to the mutual collocation among the base matrix, the metal compound and the triethanolamine, the stability of the protective agent and the protective effect on X rays are improved, the use amount of the metal compound in the protective agent is reduced, the safety of the protective agent is improved, and the problems of residual and pollution on the skin surface caused by difficult cleaning of the protective agent due to excessive addition amount of the metal compound are solved. The mutual coordination of the protective agent substances can promote the self-healing of cells and improve the resistance of the skin.
(4) The metal compound powder adopted by the invention has proper particle size, can greatly reduce the use amount of metal, reduces the production difficulty, has low economic cost, is green and safe, and has better industrial application prospect.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings that are needed in the embodiments or the description of the prior art will be briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and other drawings can be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 shows micro-CT imaging results of nude mice with the X-ray protectant provided by the examples and comparative examples of the invention; wherein # 0 is a whole body no-smear group; no. 1 is a whole body coating film X-ray protective agent (50 percent) for nude miceBi 2 O 3 500 nm); no. 2 is nude mouse whole body smearing X-ray protective agent (50% Bi) 2 O 3 500 nm); 3# is a protective cream for whole body smearing and import of nude mice
FIG. 2 shows the X-ray protectant pairs provided by examples and comparative examples of the invention 125 SPECT imaging results of I; wherein the control group is a basal matrix; the administration group is X-ray protective agent.
FIG. 3 shows the cases of acute radiation skin injury in rats by X-rays according to the examples and comparative examples of the present invention, wherein FIG. 3a is a basal matrix group, FIG. 3b is a 67% bismuth oxide group, FIG. 3c is a 50% bismuth oxide group, and FIG. 3d is an import protectantFigure 3e scores mice skin lesions for different protectants.
FIG. 4 is a graph showing the intestinal radiation of mice after whole body irradiation with X-rays according to examples and comparative examples of the present invention, wherein FIG. 4A is a photograph of colon of mice; fig. 4B is a photograph of the whole body of a nude mouse after 4 days of whole body irradiation; FIG. 4C is a nude mouse small intestine H&E, dyeing the photo; figure 4D is body weight and colon length of mice under different protective agents; a is a control group which is not smeared with protective agent and is subjected to false irradiation; b is nude mice coated with basic matrix; c is the application of X-ray protective agent (50% Bi) 2 O 3 2 μm) of nude mice; d is the application of X-ray protective agent (50% Bi) 2 O 3 500 nm).
Fig. 5 shows radiation protection of hematopoietic system of mice after 4Gy whole body irradiation for 10 days by using the X-ray protective agent according to the embodiment of the present invention, wherein fig. 5a shows the effect of different protective agents on leukocytes, and fig. 5b shows the effect of different protective agents on erythrocytes. Ctrl is a pseudo-irradiation group, VEH is a base matrix, 10% Bi of an X-ray protecting agent, 25% Bi of an X-ray protecting agent, 50% Bi of an X-ray protecting agent, bi-rubber is a bismuth-containing rubber, wherein 10% Bi, 25% Bi and 50% Bi respectively represent Bi 2 O 3 The mass ratio of the X-ray protective agent is 10%, 25% and 50%.
Detailed Description
In order to facilitate an understanding of the novel X-ray protective agent of the present invention, a more complete description of the novel X-ray protective agent of the present invention will now be given, without thereby limiting the scope of the invention.
A preparation method of a novel X-ray protective agent, which comprises the following steps: dissolving the phase A (hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer, acrylic acid (ester) or C10-30 alkanol acrylate cross-linked polymer, glycerol and carbomer) in water, heating to 80-85 ℃, and stirring to uniformly disperse the phase A; adding the B phase (methyl glucitol polyether, jojoba esters, squalane, mineral oil and ethyl hydroxybenzoate) and triethanolamine into an oil pot, heating to 80-85 ℃ for dissolution, and stirring to uniformly disperse the B phase and the triethanolamine; pumping the phase A into an emulsifying pot, pumping the mixture of the phase B and triethanolamine into the oil pot under the condition of rapid stirring, emulsifying and homogenizing for 5-8 minutes, preserving heat and stirring for 25-30 minutes, then cooling to 60 ℃ for the first time, adding bismuth trioxide powder or barium sulfate powder and deionized water to prepare a metal compound suspension, stirring uniformly at normal temperature, cooling to 40 ℃ for the second time, stirring uniformly to obtain a cream-like protective agent, discharging, filling and packaging, sterilizing by irradiation, and warehousing after inspection is qualified.
We have further carried out test experiments on the prepared X-ray protectant:
stability test of X-ray protectant at high and low temperatures: stability at normal temperature: 10g of the X-ray protective agent is taken and put into a centrifuge tube, and the centrifuge tube is centrifuged at 4000r/min for 15min and then is observed; stability at high temperature: taking an X-ray protective agent, placing the protective agent in a 55 ℃ oven for 6 hours, taking out the protective agent, and observing the property change of the protective agent after a sample is placed at room temperature; stability at low temperature: the X-ray protective agent is placed in a refrigerator at the temperature of minus 15 ℃ for 24 hours respectively, taken out, and the sample is placed at room temperature to observe the property change of the protective agent.
Safety test of X-ray protectant: 30 volunteers who met the test requirements between 18 and 60 years old were selected as subjects. The selected area is not more than 50mm 2 Pass plaque test at a depth of about 1mmAnd (5) equipment. The test object is placed in the plaque laboratory in an amount of about 0.020g to about 0.025g. The patch test with the test object was applied to the forearm of the subject on the curved side with hypoallergenic tape, and applied to the skin with gentle palm pressure for 24 hours. Skin reactions were observed according to the following table criteria for 30min (after the disappearance of the indentations), 24h and 48h, respectively, after removal of the subject plaque tester, and observations were recorded.
Detection of X-ray protective effect of X-ray protective agent: the nude mice are anesthetized by injecting anesthetic, and are respectively smeared with protective agent-free and smeared with X-ray protective agent (50% Bi) according to different groups (TOP, X-ray and CT) 2 O 3 500 nm) and application of an inlet protectantWhole body scanning using micro-CT, instrumental parameters: 70KVp; the power is 270 muA, 300ms.
X-ray protective agent pair 125 X-ray protection effect detection of I: after anesthesia of nude mice, X-ray protective agent (50% Bi) is applied to the whole body 2 O 3 500 nm) or basal matrix, tail vein injection 125 After solution I, mediso was used TM SPECT/CT imaging performed SPECT scans and radioactivity analysis.
Detection of X-ray protective properties of X-ray protective agent: different proportions of X-ray protective agent and imported protective agentRespectively smearing on a single-layer plastic film with the thickness of 5mm, placing a plurality of pyroelectric sheets below, irradiating with an X-ray irradiation instrument (the voltage is 70kv, the current is 5mA, the irradiation time is 30S), the irradiation dose is 0.5Gy, collecting the pyroelectric sheets after irradiation, detecting the pyroelectric output by a photomultiplier after heating, and reading the radiation dose value.
Detection of acute radiation skin injury effect of X-ray protectant on rats: SD rats (180+ -20 g), n=4, were randomly grouped, and after anesthesia, the rat rear buttocks were subjected to single local irradiation with X-rays generated by a linear accelerator at a dose of 4.05Gy/min and an irradiation dose of 40Gy, according to the respective protective agents and base substrates of the different groups. Animals were observed for body weight after irradiation and scored for localized skin lesions.
Detection of protective effect of X-ray protective agent on whole-body radiation intestinal damage of nude mice: the nude mice (18 g.+ -. 2, female) were randomly grouped according to body weight, and then were subjected to pseudo-irradiation in control group (a), basal matrix (b) and X-ray protective agent (50% Bi) 2 O 3 2 μm) (c), X-ray protective agent (50% Bi) 2 O 3 500 nm) (d), performing X-ray irradiation with 12Gy whole body irradiation (dose rate of 1.22 Gy/min), and taking intestinal tissue 4 days after irradiation for observation.
Protective effects of X-ray protectants against systemic radiohematopoietic injury in mice: c57 mice (18 g+ -2 g, female) were randomly grouped according to body weight, and then respectively coated with different protectants, wherein Ctrl is a pseudo-irradiation group, VEH is a base matrix, 10% Bi (500 nm) by mass of X-ray protectant, 25% Bi (500 nm) by mass of X-ray protectant, 50% Bi (500 nm) by mass of X-ray protectant, bi-rubber is bismuth-containing rubber (lead equivalent is not less than 0.25mmPb at 120 kV), wherein 10% Bi, 25% Bi and 50% Bi are respectively 10% Bi 2 O 3 、25％Bi 2 O 3 And 50% Bi 2 O 3 . The mice of each group were subjected to X-ray irradiation with a 4Gy whole body irradiation (dose rate of 1.0 Gy/min) and blood was collected for 2 days before irradiation and 10 days after irradiation, respectively, to detect peripheral blood-related indicators.
5 sets of X-ray protective agents of different formulations were prepared by the preparation method of the X-ray protective agent described above, as shown in Table 1.
TABLE 1X-ray protectants of different formulations
| Raw material name | Formula 1 | Formulation 2 | Formulation 3 | Formulation 4 | Formulation 5 |
| Bismuth trioxide/barium sulfate | 50％ | 50％ | 50％ | 50％ | 50％ |
| Hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer | 0.5％ | — | — | 0.5％ | 1.5％ |
| Acrylic acid (esters) C10-30 alkanol acrylate cross-linked polymers | — | — | 0.3％ | 0.3％ | 0.3％ |
| Glycerol | 10％ | 10％ | 5％ | 5％ | 5％ |
| Carbomer 940 | 0.2％ | 0.2％ | 0.5％ | 0.5％ | 0.5％ |
| Methyl glucitol polyether-20 | 1.0％ | 1.0％ | 1.0％ | 1.0％ | 1.0％ |
| Jojoba esters | 0.5％ | 0.5％ | 1.0％ | 1.5％ | 1.5％ |
| Squalane (Squalene) | 2％ | 2％ | 2％ | 2％ | 2％ |
| Mineral oil | 2％ | 2％ | 2％ | 2％ | 2％ |
| Ethylparaben (P-ethyl) | 0.1％ | 0.1％ | 0.1％ | 0.1％ | 0.1％ |
| Triethanolamine salt | 0.5％ | 0.5％ | 1.0％ | 1.0％ | 1.0％ |
| Deionized water | Allowance of | Allowance of | Allowance of | Allowance of | Allowance of |
In Table 1 above, hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer (Sepimac ZEN, cosmetic grade) (active > 80%) was purchased from Sibirch, france; acrylic/C10-30 alkanol acrylate cross-linked polymer (Acrypol ELT-2020, content > 98%) was purchased from Guangzhou macrobiosciences Co., ltd; jojoba esters @JP-C) (active content > 95%) purchased from Beijing Huamei reciprocal biochemical industry; ethylparaben (medical, content > 99%) was purchased from Sichuan Hengcheng Yuan Biotech Co.
TABLE 2X-ray protectant stability results
| Prescription of prescription | Centrifugal test | High temperature test | Low temperature test |
| 1 | No abnormality | The protective agent dries and becomes coarse | No abnormality |
| 2 | No abnormality | The protective agent becomes thinner and becomes liquidity | No abnormality |
| 3 | No abnormality | Consistency reduction of protectant | No abnormality |
| 4 | No abnormality | Good shape | No abnormality |
| 5 | No abnormality | The protective agent dries and becomes coarse | No abnormality |
The stability of the protective agents with 5 different proportions in the table 1 at high temperature and low temperature is tested, the test results are shown in the table 2, and the X-ray protective agents after low temperature treatment are found to have no demulsification layering phenomenon, have no obvious shape change and can resist low temperature; in the X-ray protective agent subjected to high temperature treatment, the compositions 1 and 5 are dehydrated and roughened, the consistencies of the compositions 2 and 3 are reduced to be in a flowing liquid state, and the composition 4 has no obvious character change compared with similar samples placed at room temperature. It is believed that this is probably because formulation 4 is still stable at high temperatures due to the combination of hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer with the acrylic acid (ester) type/C10-30 alkanol acrylate cross-linked polymer, which promotes the rheology and superior stability of the protectant. However, although formulation 5 had a combination of these two materials, the excess hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer, the higher molecular weight of hydroxyethyl acrylate/sodium acryloyldimethyl taurate, resulted in a too thick protectant, and we found that formulation 5 was also thicker and less coatable during the preparation process. Glycerin is often used as a dispersing agent and a humectant in the protective agent, and when the protective agent lacks the mutual collocation of hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer and acrylic acid (esters) and C10-30 alkanol acrylate cross-linked polymer, the stability and rheological property of the protective agent cannot be improved even if excessive glycerin is added.
TABLE 3 skin response grading Standard for skin seal Patch test
We further studied the safety of the X-ray protectant and judged the effect of the X-ray protectant on the skin of the subject according to table 3. Skin reactions were observed at 0.5, 6, 12, 24, 48 hours, respectively, with 0 cases showing skin erythema, pimples, blisters, etc. adverse reactions, and all subjects passed the patch test. The X-ray protective agent (formula 4) provided by the invention has high safety and no stimulation. Although triethanolamine in the protective agent can promote the healing capacity of tissues, eczema can be easily caused, carbomer in the protective agent can not only enhance the resistance capacity of skin, but also has certain anti-inflammatory and bactericidal effects, and the safety of the protective agent is improved by the mutual coordination of substances in the protective agent.
The X-ray protective agent of the formula 4 is selected for detecting the protective effect of X-rays, and the result is shown in figure 1, and according to the scanning result of Micro-CT scanning, the X-ray protective agent of the invention can obviously block the radiation generated by TOP ionizing radiation, X-rays and CT imaging, and the blocking effect of the X-ray protective agent is similar to that of imported productsEquivalent.
We also selected the X-ray protectant pair of formulation 4 125 I, the X-ray protective effect is detected, and the result is shown in figure 2, the X-ray protective agent can obviously shield the radionuclide 125 The intensity of the rays generated by the I is reduced by 98% compared with that of a control group, and the shielding effect is obviously improved.
TABLE 4 transmittance of X-ray protective Agents to X-rays at different ratios
We selected the X-ray protection performance test for different metal compounds and the results are shown in table 4. Wherein Bi of 100nm, 500nm and 2 μm is selected 2 O 3 And 500nm BaSO4 to make different X-ray protective agent, and imported productWith metal compounds, the protective effect of (a) was comparedThe ratio of the protective agent to the base matrix is increased, the protective effect of the protective agent is enhanced, when the mass ratio of the metal compound to the base matrix is 1:1, the barium sulfate and the bismuth oxide both have obvious X-ray protective effect, wherein the protective effect of the bismuth oxide is better, and when Bi 2 O 3 When the mass ratio of the base matrix is higher than 1:1, the X-ray protective agent (Bi 2 O 3 The mass ratio of the basic matrix is 1:1) and the imported product (Bi) 2 O 3 The mass ratio of the base matrix is 5.5:1) and the transmittance is equivalent. The protective agent of the invention not only reduces the addition amount of the metal compound, but also keeps high protective property.
We have also studied the quality of the base matrix and Bi 2 O 3 The better proportion of the mass, we find that under the same particle diameter, the protective effect of the protective agent on X-rays is reduced along with the increase of the mass of the basic matrix; we further selected Bi 2 O 3 50% by mass of an X-ray protective agent, bi 2 O 3 67% by mass of X-ray protective agent, base matrix and imported productThe X-ray local irradiation is carried out on the skin of the nude mice, and the result is shown in figure 3, the 40Gy X-ray local irradiation can cause obvious skin injury of the rats (basal matrix coated nude mice) and is manifested by symptoms such as red spots, hair loss, wet peeling, ulcers and the like of the irradiated areas, and the X-ray protective agent of the invention is compared with the productExhibits more remarkable protective effect on the skin after X-ray irradiation, remarkably reduces the symptom of radioactive skin injury, and uses Bi 2 O 3 The X-ray protective agent with the mass ratio of 67% shows better protective effect. It is considered that the addition of an appropriate amount of the metal compound to the X-ray protective agent can enhance the protective effect of the protective agent, but when the addition amount is excessive, the dispersion of the metal compound in the base matrix is affected uniformly, and the problem of the metal compound residue is caused, resulting in the peelingSkin damage, when added in too small an amount, can result in a large area of absence of metal compounds in the applied protectant, thereby reducing the protective effect of the protectant. We further selected that the mass ratio of the metal compound in the X-ray protective agent is 50% -70%.
We have found that when the particle size is smaller, the shielding function of the shielding agent against X-rays is better, probably because the particle size is too large, which may affect the uniformity of coating. As can be seen from Table 1, bi having different particle diameters 2 O 3 The difference of the protective effect among the X-ray protective agents is not large, the influence of the addition amount of the metal compound is far greater than the influence of the particle size of the metal compound, and in order to avoid that small-particle-size metal easily enters the skin to cause damage to the body, the particle size of the metal compound is further selected to be 400-600nm.
The protection effect of X-ray protective cream on the whole body radiation intestinal injury of nude mice was also studied, and the results are shown in FIG. 4, in which the mice were respectively subjected to pseudo irradiation (a), basal matrix coating (b) and X-ray protective agent coating (50% Bi) 2 O 3 2 μm) (c), X-ray protective agent (50% Bi) 2 O 3 500 nm) (d), the body weight of the mice before the experiment was (18.+ -.2) g. Wherein, the mice in the sham irradiation group have the weight increase and the colon length is the longest, and the mice have the most weight decrease and the colon length is the shortest after the mice are smeared with the basic matrix, thus the X-ray can cause damage to the small intestine tissues of the mice; we further compared Bi of different particle sizes 2 O 3 The X-ray protective effect of the X-ray protective agent of (a) on X-rays, it was found that the protective agent of group d (50% Bi 2 O 3 500 nm) can significantly reduce weight loss in nude mice caused by acute radiation injury, and also can significantly reduce intestinal inflammatory reaction, restore colon length reduction, and group c protectant (50% Bi) 2 O 3 2 μm) the body weight of the mice after the application was reduced, and the colon length of the mice in group c was also comparable to the colon length of the mice in group b. The results in Table 1 are also confirmed that too large a metal particle size may affect the uniformity of the protectant coating, resulting inThe protective effect is reduced.
As a result of the protective effect of the X-ray protective agent on the damage to the whole body radiohematopoietic system of mice, as shown in FIG. 5, different protective agents were applied to mice, wherein Ctrl is a pseudo-irradiation group, VEH is a base matrix, 10% Bi (500 nm) by mass of the X-ray protective agent, 25% Bi (500 nm) by mass of the X-ray protective agent, 50% Bi (500 nm) by mass of the X-ray protective agent, and Bi-rubber is a bismuth-containing rubber. From the illustration of FIG. 5, it can be seen that the X-ray protectant of the invention significantly reduces the decrease in white blood cells and platelets caused by acute radiation injury, in Bi 2 O 3 The protective agent with the mass ratio of 50 percent of the highest has the best effect of protecting white blood cells and red blood cells and is obviously superior to bismuth-containing rubber.
In conclusion, the X-ray protective agent disclosed by the invention is finer in texture and proper in consistency, can protect the skin from direct and indirect damage caused by X-rays, and has a good treatment effect on preventing radioactive skin inflammation caused by the X-rays.
It should be noted that the above-mentioned embodiments are only preferred embodiments of the present invention, and are not intended to limit the present invention, and any modifications, equivalent substitutions, improvements, etc. within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. The X-ray protective agent is characterized by comprising a base matrix, a metal compound, triethanolamine and the balance of deionized water, wherein the mass ratio of the base matrix to the X-ray protective agent is 8.5-18.6%, the mass ratio of the metal compound to the X-ray protective agent is 10-70%, the mass ratio of the triethanolamine to the X-ray protective agent is 0.2-1% and the balance of deionized water;
the base matrix consists of an A phase and a B phase, wherein the mass ratio of the A phase to the B phase is (4.4-7.6) to (4.1-11); wherein the phase A consists of hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer, acrylic acid (esters) type/C10-30 alkanol acrylate cross-linked polymer, glycerin and carbomer, the mass ratio of the hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer to the acrylic acid (esters) type/C10-30 alkanol acrylate cross-linked polymer to the glycerin to the carbomer is (0.1-0.5): (0.2-0.6): (4-6): (0.1-0.5); the phase B consists of methyl glucitol polyether, jojoba esters, squalane, mineral oil and ethylparaben, wherein the mass ratio of the methyl glucitol polyether to the jojoba esters to the squalane to the mineral oil to the ethylparaben is (0.5-1.5): 0.5-2): 2-4): 1-3: 0.1-0.5;
the metal compound is barium sulfate and/or bismuth oxide.
2. An X-ray protective agent according to claim 1, wherein the particle size of the metal compound is controlled between 2 μm and 10nm.
3. An X-ray protective agent according to claim 1, wherein the particle size of the metal compound is controlled to be 400nm to 600nm.
4. An X-ray protective agent according to claim 1, wherein the mass ratio of the base matrix in the X-ray protective agent is 10% to 15% by mass; the mass ratio of the metal compound in the X-ray protective agent is 50% -70% and the mass ratio of the triethanolamine in the X-ray protective agent is 0.5% -1%.
5. A process for preparing the X-ray protective agent according to any one of claims 1 to 4: dissolving the phase A in water, heating, and stirring to uniformly disperse the phase A; adding the B phase and the triethanolamine into an oil pan for heating and dissolving, and stirring to uniformly disperse the B phase and the triethanolamine; pumping the phase A into an emulsifying pot, pumping the mixture of the phase B and triethanolamine into the oil pot under the condition of rapid stirring, emulsifying, homogenizing, preserving heat, stirring, cooling for the first time, adding a metal compound and deionized water to prepare a metal compound suspension, stirring uniformly, cooling for the second time, stirring uniformly, discharging, filling, packaging, sterilizing by irradiation, and warehousing after inspection is qualified.
6. The method for preparing an X-ray protective agent according to claim 5, wherein the a phase is dissolved in water and heated at 80-85 ℃; the temperature of the oil pan for heating and dissolving is 80-85 ℃; the time of emulsification and homogenization is 5-8 minutes, and the time of heat preservation and stirring is 25-30 minutes; the temperature is reduced to 60 ℃ for the first time; and cooling to 40 ℃ for the second time.
7. Use of an X-ray protective agent according to any one of claims 1 to 4 for the manufacture of a product for preventing radiation damage to the body caused by X-rays.
8. The use of claim 7, wherein the injury comprises one or more of a skin injury, a digestive system injury, and/or a hematopoietic system injury;
the source of X-ray comprises C-arm X-ray machine, digital X-ray photography system, mammary X-ray machine, X-ray generated by panoramic dental film machine medical imaging equipment, and radioactive particle iodine 125 Palladium (Pd) 103 Iridium (Iridium) 192 One or more of the X-rays are generated during particle implantation radiotherapy.
9. The X-ray protective agent according to any one of claims 1 to 4, wherein the dosage form of the X-ray protective agent comprises one of an ointment, a liniment, a patch, and a film coating agent.
10. The X-ray protective agent according to claim 9, wherein the ointment comprises one of cream, gel, paste.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211299812.1A CN115487172B (en) | 2022-10-24 | 2022-10-24 | X-ray protective agent and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211299812.1A CN115487172B (en) | 2022-10-24 | 2022-10-24 | X-ray protective agent and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115487172A CN115487172A (en) | 2022-12-20 |
| CN115487172B true CN115487172B (en) | 2023-07-25 |
Family
ID=84474544
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211299812.1A Active CN115487172B (en) | 2022-10-24 | 2022-10-24 | X-ray protective agent and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115487172B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105535020A (en) * | 2016-01-25 | 2016-05-04 | 苏州爱瑞德医疗科技有限公司 | Medical X-ray protective cream and preparation method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9114121B2 (en) * | 2010-01-07 | 2015-08-25 | Bloxr Solutions, Llc | Radiation protection system |
-
2022
- 2022-10-24 CN CN202211299812.1A patent/CN115487172B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105535020A (en) * | 2016-01-25 | 2016-05-04 | 苏州爱瑞德医疗科技有限公司 | Medical X-ray protective cream and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 重组人表皮生长因子凝胶联合三乙醇胺乳膏 治疗腹部放射性皮炎60例;贺清波等;《陕西医学杂志》;第45卷(第3期);350-351 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115487172A (en) | 2022-12-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO2010006722A1 (en) | Contrast agent-reinforced radiotherapy having high-output tubes | |
| CN105943558A (en) | Application of periplaneta americana in preparation of drug for preventing and treating radiation-induced damage | |
| CN101015522A (en) | Cream for treating psoriasis and its preparing process | |
| EP2717963B1 (en) | Multilayer structure for epidermal radionuclide therapy | |
| CN115487172B (en) | X-ray protective agent and preparation method thereof | |
| CN108066279A (en) | A kind of medicinal external emulsifiable paste composition containing benzene alkene not moral | |
| Lal et al. | Hemangiopericytoma: report of three cases regarding role of radiation therapy | |
| RU2642957C2 (en) | Liposome, pharmaceutical composition and drug for treatment of local radiation skin lesions, liposome application and method for local radiation skin lesions treatment | |
| CN103446329A (en) | Application of tenuifolia-fructus forsythia soup to preparation of medicine for preventing and treating acute radiodermatitis | |
| Leiba et al. | Cushing’s disease coexisting with a single macronodule simulating adenoma of the adrenal cortex | |
| Voth et al. | Biological dosimetry after yttrium-90 citrate colloid radiosynoviorthesis | |
| Joshi et al. | Reduced radiation during cardiac catheterization of infants using acquisition zoom technology | |
| CN110680856A (en) | Eczema fumigation powder | |
| Kailasam et al. | Trichostasis spinulosa | |
| CN115814008B (en) | Traditional Chinese medicine line for treating perianal abscess and application thereof | |
| US6454695B1 (en) | Therapeutic instrument for treating or relieving psoriasis, atopic dermatitis, articular rheumatism and/or cancer or preventing the progress of these diseases and method of utilization thereof | |
| CN107822983A (en) | A kind of radiation proof containing Ganoderma spore extract, acne-removing composition and preparation method thereof | |
| Haddadi et al. | Investigation of Erythema, Radiation Dose, and Radiation-Induced Apoptosis in the Peripheral Blood Lymphocytes of Patients Treated with Radiofrequency Catheter Ablation. | |
| CN101904831B (en) | Application of alkannin and compositions thereof | |
| CN102018738B (en) | Application of scandent schefflera stem and leaf in preparation of radiation-proof health care products | |
| Uhlmann | Significance and Management of Radiation Injuries | |
| WO2022194168A1 (en) | Use of traditional chinese medicine composition in preparation of drug for preventing or treating chronic skin ulcer | |
| RU2697847C1 (en) | X-ray diagnostics contrast agent | |
| Papaloucas | P32 uptake in treated and untreated cervix uteri carcinoma | |
| Kim | Verification of the Protective Effect of Functional Shielding Cream for the Prevention of X-ray Low-dose Exposure |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |