CN114259503A - Povidone-iodine solution for human and preparation method thereof - Google Patents
Povidone-iodine solution for human and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a povidone iodine solution for human use, which is prepared by adopting the following formula: 5-10kg of povidone iodine, 0.5-1.0kg of potassium iodide, 6-10kg of betaine, 0.2-0.5kg of D-panthenol, 30-65kg of water and the balance of glycerol are prepared into a solution with the total amount of 100L. The preparation method comprises the steps of dissolving, mixing and the like in a corrosion-resistant reaction kettle in steps at a certain stirring speed by using corrosion-resistant stirring equipment. The povidone iodine solution for human use has the advantages of scientific and reasonable formula composition and unique process, has the effects of promoting wound healing and moistening skin, contains 0.5-1.0% of effective iodine, can be used for persistently sterilizing and disinfecting, killing intestinal pathogenic bacteria, pyococcus, pathogenic saccharomycetes and other common pathogenic bacteria, preventing secondary infection, resisting bacteria and relieving itching, is free from staining clothes when in use, is nontoxic through mouth, has no stimulation to skin, wounds and mucous membrane eyes, and does not leave scars after wound healing.
Description
Technical Field
The invention relates to the technical field of disinfectant preparations, in particular to a preparation method of povidone iodine disinfectant for human use.
Background
The patient is difficult to bump and collide in life, and the wound is easy to be infected when not treated in time; eczema, allergy, oral ulcer, repeated attacks afflict many people; beriberi, onychomycosis and skin pruritus are difficult to endure, and the healthy life is influenced; the old people have cracked skin of hands and feet and bed sores for a long time, and are bitter; people often apply some liquid medicine containing alcohol to meet the problems, and the irritation is strong; the use of the band-aid has poor air permeability; skin infection is caused by insufficient sterilization; even some drugs contain hormones and cause even greater damage if abused.
The povidone iodine is a complex of polyvinylpyrrolidone-K30 (PVP-K30) and iodine, takes active iodine as a main sterilization component, has strong killing effect on common bacteria such as staphylococcus aureus, pseudomonas aeruginosa, escherichia coli, candida albicans, hepatitis B virus, trichomonas vaginalis, spores and the like, has the advantages of small volatility, good water solubility, mild and lasting effect and safe use, and is a novel external disinfectant and bactericide with high efficiency, broad spectrum and low toxicity.
Iodine tincture (commonly called iodine tincture) has strong sterilizing capability (no surface activity and slow release effect), has obvious stimulation effect on mucosa, and damages skin, mucosa and the like after long-term use. Has strong irritation, and can be used for skin disinfection, which requires deiodination, otherwise skin foaming or allergy can be caused. The skin is yellow and dyed, the wound is easy to burn, and the wound healing time is long; has strong corrosivity, is used for disinfecting the surface of the intact skin, and cannot be used for disinfecting the mucous membrane.
Yellow dye is the phenomenon that the iodine-containing solution is difficult to remove by using clean water after contacting with an object for a certain time in the using process. At present, iodine-containing solutions are known to cause yellow staining of the skin and ground during use. In the operating room, the in-process that iodine solution used, inevitably will spill it on the floor, because the operation process generally needs more than 6 hours, even the personnel of keeping a public place clean at this moment clears away the floor and cleans, because the yellow dyeing characteristic of iodine solution, reuse clear water is difficult to detach this moment, is assisted with the iodine scavenger, though can solve the yellow dyeing, but the cost can increase, and the operation is also more loaded down with trivial details, and the time of keeping a public place clean prolongs, has reduced the utilization ratio of operating room. In addition, after the time, the iodine-containing solution drops on the floor, which causes irreversible yellow pollution and damage to the floor, greatly affects the vision of doctors, seriously affects the safety of the operation, and greatly reduces the service life of the floor.
The iodophor has strong bactericidal power (good surface activity and strong slow release effect), is safe and acidic, and has certain stimulation effect on mucous membrane. After the skin is used, the skin can feel dry and itchy when healing.
The influence of pH value on the stability of the povidone-iodine solution is considered by Zhouqingmin et al in the Chinese dairy 2014 phase 1P 46-48 and the influence of pH value on the stability of the povidone-iodine solution, the decrease range of effective iodine content of the povidone-iodine solution with the initial pH value of 3.5-6.0 is slowed down, and the stability of the solution can be enhanced to different degrees; the povidone iodine solution with the initial pH values of 5.0 and 5.5 has the best stability effect, but the adjusting reagent used by the povidone iodine solution is sodium hydroxide, the sodium hydroxide is strong alkali, the pH value and the effective iodine content are obviously reduced after the povidone iodine solution is stored for 4 weeks, and the good stability of the solution cannot be maintained.
The disclosed invention CN201910420578.5 adopts a complex process to prepare polyvinylpyrrolidone, then uses the special polyvinylpyrrolidone to prepare povidone iodine by the complex process, mixes the obtained povidone iodine and glycerin to obtain the povidone iodine composition, the solvent N-vinyl pyrrolidone, the initiator azodiisobutyronitrile or the hydrogen peroxide-ammonia water solution used in the preparation process need complex equipment and steps of water bath heating, constant temperature reflux and the like, and the prepared povidone iodine is powder and is not well dispersed in glycerin.
The invention CN200710041165.3 is disclosed, wherein the pH value is adjusted by sodium hydroxide, and a phosphate buffer solution is added, the phosphate buffer effect is limited, the phosphate buffer solution can be stable in a short period, but the requirement of longer shelf life is not met.
The disclosed invention CN201810639080.3 discloses that povidone iodine is prepared into a slow-release medicine film, the dissolution time of the slow-release medicine film is 36 hours, the application scene of the slow-release medicine film is limited to be used for mycotic vaginitis which needs to be long-lasting, the slow-release medicine film cannot be widely applied to common small wounds and various wounds which do not need to be slowly released for 36 hours, the waste of effective iodine components in a slow-release tablet is caused, the slow-release medicine film cannot be well attached to the wounds and is extremely easy to drop, the slow-release medicine film is adhered to an object after meeting a small amount of water, and the subsequent yellow staining is difficult to remove.
CN201610382457.2 was disclosed as an invention in which ascorbic acid was used as an antioxidant, ascorbic acid was reductive and povidone-iodine was oxidative, and both reacted, and even though the solid state could be temporarily stabilized, the solution was formed and then reacted.
According to the invention disclosed in the invention CN99114144.X, water in the prepared povidone-iodine solution still accounts for the main component, the influence of glycerin on the stability of povidone-iodine is not reflected, and if the glycerin ratio is adjusted to the ratio disclosed by the invention, the benzyl alcohol and the polyvinylpyrrolidone cannot play a role of a stabilizer, so that the shelf life of the povidone-iodine solution is maintained for 36 months.
The invention CN03131706.5 has been disclosed, in which Tween 80 and propylene glycol are added to increase the dispersion degree and have proper viscosity, but the problem that the pH of povidone-iodine solution is kept stable between 3.5 and 6.5 within the shelf life of 36 months is still not solved, tests prove that the formula composition can only be kept stable for a short time, the pH is less than 3.5 after 6 months, and the stability of effective iodine content is influenced by too low a pH value.
The invention CN201810012624.3 has been disclosed, the chitosan added in the invention can only enhance the slow release effect, but can not achieve the effect of buffering the pH, the acetic acid is added in the invention, the pH of the invention is adjusted to be 3.5-4.5, when the chitosan is applied to ulcerated wounds, the chitosan still has irritation to the skin, and acute eye irritation has damage from slight irritation to irritation.
The invention CN202110571717.1 has been disclosed, which is applied to animals, adjusts pH, and also uses corresponding thickening agent to increase adhesiveness, but the thickening agent adopted in the invention is hydroxypropyl methylcellulose, although the thickening agent has certain viscosity, the moisture retention performance is inferior to that of glycerin, the solution with high content of 10% effective iodine is too viscous, the granular feeling of hydroxypropyl methylcellulose appears along with the prolonging of storage time, the moisture retention performance of the diluted povidone iodine solution with 1% effective iodine is also greatly reduced, and if sodium tripolyphosphate is used as the regulator in the formula of adding glycerin, the viscosity of the product is greatly reduced by adding a small amount of sodium tripolyphosphate, and the use of the product is influenced.
Disclosure of Invention
Based on the above, the invention provides the povidone iodine solution for the human and the preparation method thereof, the formula composition is scientific and reasonable, the process is unique, the povidone iodine solution is a solution with proper viscosity and the content of 5-10% of povidone iodine, can be used for durably sterilizing and disinfecting, killing intestinal pathogenic bacteria, pyogenic coccus, pathogenic saccharomycetes and other common pathogenic bacteria, preventing secondary infection, resisting bacteria, relieving itching, promoting wound healing and moistening skin, is free from staining clothes when in use, is non-toxic by mouth, has no stimulation to skin, wounds and mucous membrane eyes, and does not leave scars after the wound is healed.
The invention is realized by the following technical scheme:
the povidone iodine solution for human use is prepared from the following components in formula: 5-10kg of povidone iodine, 0.5-1.0kg of potassium iodide, 6-10kg of betaine, 0.2-0.5kg of D-panthenol, 30-65kg of water and the balance of glycerol are prepared into a solution with the total amount of 100L.
The povidone iodine is formed by forming a micro cavity-coating carrier by povidone (PVP) and complexing iodine (I) ions in a cavity of the microcapsule.
The potassium iodide is a pharmaceutical grade auxiliary material, and the content is more than or equal to 99.0 wt% of a dry product. The weight part ratio of the povidone iodine to the potassium iodide is 10: 1.
the glycerol is a pharmaceutical grade auxiliary material and contains C3H8O3≥95.0wt％。
The content of betaine is C5H11NO2Calculated by more than or equal to 98.0wt percent.
The content of D-panthenol is more than or equal to 98.0 wt% on a dry basis.
The povidone iodine for human use has the density of 1.17g/mL-1.28g/mL and the pH of 4.5-5.5.
A preparation method of povidone iodine solution for human use adopts the following components: 5-10kg of povidone iodine, 0.5-1.0kg of potassium iodide, 6-10kg of betaine, 0.2-0.5kg of D-panthenol, 30-65kg of water and the balance of glycerol are prepared into solution with the total amount of 100L; the preparation steps are as follows:
the method comprises the following steps: weighing water with a prescribed amount into a corrosion-resistant reaction kettle, adding potassium iodide with a prescribed amount, starting the reaction kettle, adjusting the rotation speed of a stirring paddle to 1200r/h, adding betaine with a prescribed amount after complete dissolution, and stirring and dissolving to form a body system 1;
step two: adding the D-panthenol with the prescription amount into the system 1, uniformly stirring, adding the povidone iodine with the prescription amount, and stirring for 30 minutes to form a system 2;
step three: adding the rest of glycerol into the system 2 while stirring, and stirring for 20min after completely adding to obtain povidone iodine solution for human use.
According to the preparation method of the povidone iodine solution for human use, the reaction kettle and the stirring paddle are made of corrosion-resistant materials.
After the scheme is adopted, the invention has the beneficial effects that:
(1) the adopted povidone iodine raw material forms a micro cavity-coated carrier by povidone (PVP), and iodine (I) ions are complexed in the cavity of the microcapsule to form the povidone iodine micro cavity-coated micro cavity, so that the povidone iodine micro cavity-coated micro cavity can play a strong role in disinfection by continuously releasing free iodine. Under the state of aqueous solution, due to the affinity effect of the povidone to the cell membrane, the iodine is introduced to the surfaces of pathogenic bacteria to destroy the cell membrane of the pathogenic bacteria and required nutrient substances thereof, thereby playing a role in quickly killing bacterial spores, fungi, viruses and partial protozoa.
(2) The added potassium iodide has the effect of stabilizing the effective iodine content, and particularly, the ratio of the povidone iodine to the potassium iodide in parts by weight is 10:1, so that the effective iodine content of the povidone iodine solution for people can keep within +/-10 percent of the marked amount of the effective iodine within 36 months of shelf life.
(3) The D-panthenol nursing effect on the skin is represented by a deeply penetrating humectant, the specific proportion is preferably selected, and the D-panthenol nursing agent is matched with glycerin for use, so that the growth of epithelial cells is stimulated, the healing of wounds is promoted, and the anti-inflammatory effect is achieved; can improve nail hydration and give flexibility to nail when used for treating paronychia and onychomycosis; too little D-panthenol can not play a role in deep penetration and moisture retention, and too much D-panthenol not only greatly increases the production cost, but also causes the change of the properties of the product due to the high penetration effect, and the viscosity is greatly reduced.
(4) The betaine is added, so that the effects of sterilization and improvement can be cooperated with povidone iodine, and the betaine and D-panthenol can play a role in diminishing inflammation, have good permeability and do not harm skin; at the same time, we surprisingly found that betaine can maintain the stability of the pH of the povidone-iodine in the presence of a large amount of glycerin, thereby stabilizing the effective iodine content of the povidone-iodine.
(5) The reaction kettle and the stirring paddle are made of corrosion-resistant materials, have the characteristics of acid resistance, alkali resistance and various organic solvents resistance, are almost insoluble in all solvents, and meanwhile, the material has the characteristics of high temperature resistance and extremely low friction coefficient, is suitable for the production of povidone iodine solution, and enables the dispersion to be more uniform.
(6) The povidone iodine powder is dissolved by water only, the povidone iodine is easy to agglomerate under the conventional stirring, the required dispersion time is long, the powder can also inevitably fly or the floating liquid level is not well dispersed, the corrosion-resistant reaction kettle and the stirring paddle are adopted, water, potassium iodide serving as a stabilizing agent, betaine serving as a solid regulator and D-panthenol serving as a liquid regulator are sequentially added, particularly, the D-panthenol is added firstly, and then the povidone iodine powder is added, so that the povidone iodine powder can be completely dissolved in the kettle only by stirring at the rotating speed of 1200r/h for 30min, the subsequent mixing of other materials is also only required by conventional mixing and stirring uniformly, the defect that the povidone iodine is easy to agglomerate and is not well dispersed when being dissolved in water is greatly improved, the stirring only needs low rotating speed and does not need high-rotating-speed production equipment, the production cost is reduced, and the economic benefit is improved.
(7) The prepared povidone iodine solution for human use is a liquid with effective iodine content of 0.5-1.0%, has pH of 4.5-5.5, can maintain the pH within 36 months of shelf life, and can not cause irritation when being applied to wounds with skin ulceration; but also the effective iodine stability in this pH range.
(8) Tests prove that the formula has no yellow dyeing effect on different materials (the same PVC plastic floor in an operating room, a glass culture dish in a laboratory, silk, pure cotton cloth and blended fabric), and can achieve the effect of keeping no yellow dyeing after being placed for 90 days for cleaning and wiping.
(9) Acute oral toxicity LD to SPF-grade KM mice50More than 5000mg/kg BW, actual non-toxicity and low toxicity, and the povidone iodine solution provided by the invention can be reasonably presumed to be acute and non-toxic for oral administration.
(10) Has good effect on killing escherichia coli, staphylococcus aureus, salmonella, pseudomonas aeruginosa and candida albicans. The ointment can be applied to the affected part to improve dermatitis, rash and tinea, promote wound healing, and has effects of keeping moisture and preventing chapping.
(11) ChangYongqiong is in the health of today 2014 No. 7P 391-392, and the theory of wound moist environment healing and moist treatment considers that the wound is kept moist to be beneficial to the dissolution of necrotic tissues and fibrin; the moist wound surface can protect granulation particles, is beneficial to epithelization, is not easy to form crust skin, and reduces scars; the release of various bioactive factors is kept and promoted, so that the proliferation, differentiation and displacement of cells are facilitated, and the healing is accelerated; the local moisture of the wound is kept, the exposure of nerve endings to air is avoided, and the pain is reduced; maintain the low oxygen state of the local microenvironment of the wound surface and relatively low oxygen partial pressure, and promote the formation of blood vessels and granulation tissues. Therefore, the povidone iodine solution for human use can prevent the wound from being infected, sterilize the wound, moisten the skin, promote the wound to heal quickly and prevent the wound from developing into hypertrophic scar.
Drawings
FIG. 1-1 is a diagram showing initial characteristics of laboratory glass petri dish painting comparative example 26 and example 6;
FIG. 1-2 is a property diagram of a laboratory glass culture dish smeared for 0.5h in comparative example 26 and example 6;
FIGS. 1 to 3 are graphs showing the behavior of laboratory glass petri dishes after being smeared for 24 hours in comparative example 26 and example 6;
FIGS. 2-1 to 2-6 are views illustrating a healing process of a finger cut of a woman;
FIGS. 3-1 to 3-2 are views showing the initial wound healing and two days after nail scratching in a 6-month-old infant.
Detailed Description
Preferred embodiments of the present invention will be described in more detail below. While the following describes preferred embodiments of the present invention, it should be understood that the present invention may be embodied in various forms and should not be limited by the embodiments set forth herein.
Comparative examples 1 to 32 and examples 1 to 7: the component formulations are shown in tables 1-1 to 1-10.
Note: in the following tables, the remaining units are kg, except for the individual units.
TABLE 1-1
Tables 1 to 2
Tables 1 to 3
Tables 1 to 4
Tables 1 to 5
Tables 1 to 6
Tables 1 to 7
Tables 1 to 8
Tables 1 to 9
Tables 1 to 10
Comparative example 1(CN201910420578.5) preparation process:
(1) preparation of polyvinylpyrrolidone: heating a solvent in a water bath to 40-80 ℃, adding N-vinyl pyrrolidone and an initiator while stirring, wherein the volume ratio of the N-vinyl pyrrolidone to the solvent is 0.25-1:1, the final concentration of the initiator is 0.2% -3%, and stirring for 30-60 minutes to obtain polyvinylpyrrolidone;
the solvent is one of absolute ethyl alcohol, purified water, isopropanol and benzene;
the initiator is azodiisobutyronitrile or a hydrogen peroxide-ammonia water mixed solution, and the ratio of the hydrogen peroxide-ammonia water mixed solution is as follows: 5mL of hydrogen peroxide with the volume percentage of 30 percent and 10mL of ammonia water with the volume percentage of 10 percent;
(2) and (3) preparation of povidone iodine: fully mixing the polyvinylpyrrolidone obtained in the step (1), iodine and potassium iodide, wherein the mass ratio of the polyvinylpyrrolidone to the iodine is 4-5: 1; adding absolute ethyl alcohol while stirring until the iodine and the potassium iodide are completely dissolved, heating to 75-80 ℃, refluxing at constant temperature for 50-70 minutes, changing into a distillation device, evaporating the ethyl alcohol, drying, crushing and sieving to obtain povidone iodine;
(3) preparation of povidone-iodine composition: uniformly mixing the povidone iodine obtained in the step (2) and glycerol according to the prescription amount to obtain the povidone iodine composition.
Comparative example 2(CN200710041165.3) preparation process:
a. mixing 10% PVP-I and 1% KIO3Dissolving in purified water;
b. adjusting the pH value to 6.0 by using a NaOH aqueous solution with the concentration of 5 percent;
c. adding 3% glycerol and 10% phosphate buffer solution, and stirring;
d. adding 1% KI and stirring uniformly.
The percentage of each component is weight percentage.
Comparative example 3(CN201810639080.3) preparation process:
(1) dissolving povidone iodine in purified water;
(2) dissolving hydroxypropyl methylcellulose, glycerol and polyvinyl alcohol in purified water;
(3) adding the solution obtained in the step (1) into the solution obtained in the step (2), and uniformly mixing;
(4) preserving heat and removing bubbles;
(5) preparing a membrane;
(6) and (6) packaging.
Comparative example 4(CN201810639080.3) preparation process:
(1) dissolving povidone iodine in purified water;
(2) dissolving hydroxypropyl methylcellulose and glycerol in purified water;
(3) and (3) adding the solution obtained in the step (1) into the solution obtained in the step (2), and uniformly mixing to obtain the povidone iodine solution for human use.
Comparative example 5(CN201610382457.2) preparation process:
(1) mixing povidone K30 with the humidity of 5% and refined iodine according to the weight ratio of 4:1, heating at 80 ℃ for 40 hours for complexing to obtain povidone iodine, wherein the effective iodine weight percentage content of the povidone iodine is more than or equal to 14.0%;
(2) dispersing 300 parts of povidone iodine obtained in the step (1) into water with the mass being 10 times that of the povidone iodine, adding 11 parts of ascorbic acid and 20 parts of monopotassium phosphate, stirring for 20 minutes at room temperature, adding 13 parts of potassium iodide, 15 parts of potassium iodate and 10 parts of glycerol, and uniformly stirring to obtain a povidone iodine aqueous solution.
Comparative example 6(CN201810012624.3) preparation process:
1) adding acetic acid with the formula amount into purified water with the formula amount, and stirring until the acetic acid is completely dissolved;
2) taking a proper amount of the acetic acid aqueous solution prepared in the step 1), adding poloxamer according to the formula amount while stirring, uniformly stirring, and standing at 2-10 ℃ to fully swell the solution to form a uniform solution a;
3) dissolving chitosan, povidone iodine, propylene glycol and glycerol in the rest of the acetic acid aqueous solution prepared in the step 1) according to the formula amount, and uniformly stirring until the chitosan, the povidone iodine, the propylene glycol and the glycerol are completely dissolved to obtain a solution b;
4) and mixing and stirring the solution a and the solution b uniformly, aging at normal temperature for 2-12 h, and then performing sterilization treatment to obtain the povidone iodine antibacterial hydrogel.
Comparative example 7(cn99114144.x) preparation process:
firstly, povidone iodine with the prescription amount is added into polyvinylpyrrolidone with the prescription amount, stirred and diluted by adding distilled water for standby. Then adding the benzyl alcohol into the benzyl alcohol to dilute the benzyl alcohol for later use. And finally, mixing the two prefabricated solutions together and uniformly stirring to prepare the mixed povidone iodine disinfectant.
Comparative example 8(CN03131706.5) preparation process:
uniformly stirring and dissolving povidone iodine in 1/3 water to obtain solution I. Mixing glycerol and/or propylene glycol and 1/3 water, and stirring to obtain solution II. And mixing the solution I and the solution II and stirring uniformly to obtain a solution III. Dissolving potassium iodide and potassium iodate in small amount of water, adding, stirring, adding Tween-80 and correctant, adding water to desired volume, and stirring. And putting into a container with a nozzle.
Comparative example 9(CN202110571717.1) preparation process:
the method comprises the following steps: weighing potassium iodide and water according to the prescription amount, dissolving, and filling into a specific solution preparation container to form a body system 1;
step two: adding povidone iodine and ethanol with the prescribed amount into the system 1, placing an impeller of a dispersion machine at the center of a container, lowering the impeller to the lowest position, starting the machine to adjust the rotating speed to 1200r/min, and stirring for 30 minutes to form a system 2;
step three: adding hydroxypropyl methyl cellulose and sodium tripolyphosphate into the system 2, and stirring for 30 minutes to obtain the povidone-iodine solution.
The special preparation container and the dispersion machine are made of metal materials, and the surfaces of the special preparation container and the dispersion machine are provided with polytetrafluoroethylene coatings.
The special preparation container is provided with an inner barrel and an outer barrel which are sleeved together, a cooling liquid chamber is formed between the inner barrel and the outer barrel, and the cooling liquid chamber is provided with a cooling liquid inlet and a cooling liquid outlet.
Comparative example 10 (effect of pH on povidone-iodine solution stability) preparation process:
dissolving 50L pure water into 1kg povidone iodine, adding 40L water after completely dissolving, adjusting pH value to 5.0 with 5% sodium hydroxide solution, and adding to total amount of 100L while adjusting to obtain the povidone iodine solution.
Comparative examples 11-25, 27 preparation process:
the method comprises the following steps: weighing water (or ethanol) with a prescription amount into a corrosion-resistant reaction kettle, adding potassium iodide (or potassium iodate and polyvinylpyrrolidone) with the prescription amount, starting the reaction kettle, adjusting the rotation speed of a stirring paddle to 1200r/h, adding a solid regulator with the prescription amount after complete dissolution, and forming a body system 1 after stirring and dissolution;
step two: adding a prescription amount of liquid regulator into the system 1, uniformly stirring, adding the prescription amount of povidone iodine, and stirring for 30 minutes to form a system 2;
step three: adding the rest of glycerol into the system 2 while stirring, and stirring for 20min after completely adding to obtain povidone-iodine solution for human use.
The reaction vessel is a corrosion-resistant reaction kettle, and the stirring paddle of the reaction vessel also has a corrosion-resistant function.
Comparative examples 28-31, 34-39 preparation processes:
the method comprises the following steps: weighing water with a prescribed amount into a corrosion-resistant reaction kettle, adding potassium iodide with a prescribed amount, starting the reaction kettle, adjusting the rotation speed of a stirring paddle to 1200r/h, adding betaine with a prescribed amount after complete dissolution, and stirring and dissolving to form a body system 1;
step two: adding the D-panthenol with the prescription amount into the system 1, uniformly stirring, adding the povidone iodine with the prescription amount, and stirring for 30 minutes to form a system 2;
step three: adding the rest of the carrier except water into the system 2 by times while stirring, and stirring for 20min after completely adding to obtain the povidone-iodine solution for human use.
The reaction vessel is a corrosion-resistant reaction kettle, and the stirring paddle of the reaction vessel also has a corrosion-resistant function.
Comparative example 32 preparation process:
the method comprises the following steps: weighing 50kg of glycerol into a corrosion-resistant reaction kettle, adding potassium iodide according to the prescription amount, starting the reaction kettle, regulating the rotation speed of a stirring paddle to 1200r/h, adding betaine according to the prescription amount after complete dissolution, and stirring and dissolving to form a body system 1;
step two: adding the D-panthenol with the prescription amount into the system 1, uniformly stirring, adding the povidone iodine with the prescription amount, and stirring for 30 minutes to form a system 2;
step three: adding the rest of glycerol into the system 2 while stirring, and stirring for 20min after completely adding to obtain povidone-iodine solution for human use.
The reaction vessel is a corrosion-resistant reaction kettle, and the stirring paddle of the reaction vessel also has a corrosion-resistant function.
Comparative examples 26, 33 preparation process:
the method comprises the following steps: weighing 50kg of water in a corrosion-resistant reaction kettle, adding potassium iodide according to the prescription amount, starting the reaction kettle, regulating the rotation speed of a stirring paddle to 1200r/h, adding betaine according to the prescription amount after complete dissolution, and stirring and dissolving to form a body system 1;
step two: adding the D-panthenol with the prescription amount into the system 1, uniformly stirring, adding the povidone iodine with the prescription amount, and stirring for 30 minutes to form a system 2;
step three: adding the rest amount of water into the system 2 while stirring, and stirring for 20min after completely adding to obtain povidone iodine solution for human use.
The reaction vessel is a corrosion-resistant reaction kettle, and the stirring paddle of the reaction vessel also has a corrosion-resistant function.
Comparative example 40 preparation process:
the method comprises the following steps: weighing potassium iodide, povidone iodine, betaine and water according to the prescription amount at a speed of 1200r/h, stirring for 30 minutes to dissolve, observing whether the potassium iodide, the povidone iodine and the betaine are completely dissolved, and if the potassium iodide, the povidone iodine and the betaine are not dissolved, continuing stirring until the potassium iodide, the povidone iodine and the betaine are completely dissolved to form a body system 1;
step two: and D-panthenol is added into the system 1, the mixture is uniformly stirred, the rest of glycerol is added into the mixture in several times while stirring, and the mixture is completely added and stirred for 20min to obtain the povidone-iodine solution.
The specific preparation container is a corrosion-resistant reaction kettle, and a stirring paddle of the specific preparation container also has a corrosion-resistant function.
Comparative example 41 preparation process:
the method comprises the following steps: weighing the prescribed amount of water in a corrosion-resistant reaction kettle, adding the prescribed amount of potassium iodide, starting the reaction kettle, regulating the rotation speed of a stirring paddle to 1200r/h, adding the prescribed amount of betaine after complete dissolution, and stirring and dissolving to form a body system 1;
step two: in the system 1, povidone iodine with the amount of the prescription is added after being uniformly stirred, and the mixture is stirred for 30 minutes to form a system 2;
step three: adding the formula amount of D-panthenol into the system 2, adding the rest glycerol while stirring, and stirring for 20min after completely adding to obtain the povidone-iodine solution for human use.
The reaction vessel is a corrosion-resistant reaction kettle, and the stirring paddle of the reaction vessel also has a corrosion-resistant function.
Comparative example 42: iodine tincture
Dissolving potassium iodide in 2L water, adding iodine and ethanol, stirring to dissolve, and adding water to 100L.
Comparative example 43: iodine glycerin
Dissolving potassium iodide in water, adding iodine, stirring to dissolve, adding glycerol to 100L, and stirring.
Examples 1-7 preparation process:
the method comprises the following steps: weighing the prescribed amount of water in a corrosion-resistant reaction kettle, adding the prescribed amount of potassium iodide, starting the reaction kettle, regulating the rotation speed of a stirring paddle to 1200r/h, adding the prescribed amount of betaine after complete dissolution, and stirring and dissolving to form a body system 1;
step two: adding the D-panthenol with the prescription amount into the system 1, uniformly stirring, adding the povidone iodine with the prescription amount, and stirring for 30 minutes to form a system 2;
step three: adding the rest of glycerol into the system 2 while stirring, and stirring for 20min after completely adding to obtain povidone iodine solution for human use.
The reaction vessel is a corrosion-resistant reaction kettle, and the stirring paddle of the reaction vessel also has a corrosion-resistant function.
Test one: the invention relates to comparison and analysis of preparation process of povidone iodine solution
The comparison and analysis of the povidone-iodine solution preparation process related to the present invention are shown in table 2.
Note: "/" indicates no particular arrangement or requirement.
TABLE 2
As shown in Table 2, the requirements of the devices of comparative examples 2-4, 7-8 and 10 are not high, only the dissolving and stirring device is needed, and the implementation is easy, and the devices adopted in comparative examples 11-41 and examples 1-7 are improved on the basis of the dissolving and stirring device, so that the devices can resist corrosion, the production process is not complicated, and a plurality of devices and device costs are increased.
In the preparation process, potassium iodate was found to dissolve much slower than potassium iodide when prepared using the formulation of comparative example 11, requiring longer stirring time to dissolve potassium iodate, which is a hazardous chemical, and has limitations in both purchase and use, so the more easily purchased potassium iodide is preferred in the present invention.
When the preparation process of comparative example 40 is adopted for preparation, when the first step is dissolved, the potassium iodide and the povidone-iodine are simultaneously dissolved and stirred for 30min and then can not be completely dissolved, and the solution can be dissolved after at least stirring for 30min, so that the total time is increased and the dissolving effect is not as good as that of the step-by-step dissolution compared with the preparation processes adopting the methods of examples 1 to 7.
Comparative example 41 povidone iodine was added first and povidone iodine was added to D panthenol, povidone iodine rapidly swelled in water before D panthenol was added, the aqueous solution thickened, part of the powder did not disperse well, and stirring for 30min to longer time was required, which not only increased power consumption, increased production time, and poor dissolution effect compared to other examples, but also previously added D-panthenol rapidly assisted dispersion when povidone iodine powder was added due to its high permeability, and did not cause the solution to increase in consistency and not disperse well, so the present invention prefers the sequence of steps of adding D-panthenol first and povidone iodine second.
The equipment adopted by the invention can achieve the purpose of dissolution only by a common stirrer with the rotating speed of 1200r/h, a dispersion machine with high-speed operation is not needed, and good economic benefit can be achieved by less equipment investment.
And (2) test II: the invention relates to the appearance comparison of povidone-iodine solution
Povidone iodine solution for testing: prepared by the method of comparative examples 1-43 and examples 1-7.
The test results are shown in table 3:
note: "+" indicates the degree of viscosity of the solution, and more "+" indicates more viscosity. "/" indicates that the finished product is a solid and has no consistency. "-" indicates a flowing liquid that is completely non-stick.
TABLE 3
It can be seen from table 3 that comparative example 5 is unstable and reddish brown is lighter because povidone-iodine has strong oxidizing property and ascorbic acid has strong reducing property and cannot coexist in the solution;
comparative examples 2, 7, 10, 18 and 33 are reddish brown liquids with low viscosity, and cannot meet the requirement of increasing the product adhesion to the skin surface for a long time;
in comparative examples 1, 32 and 40, only glycerin is used for dispersing other solids, and the glycerin is sticky and does not disperse the solids well, and finally, povidone iodine still cannot be completely dissolved.
The other comparative examples and the examples are compared by observing other properties, except that the comparative example 6 is gel with the highest viscosity and the difference of the other viscosities is not obvious.
And (3) test III: the invention relates to the pH value and stability condition of povidone iodine solution
Test samples: prepared by the method of comparative examples 4, 8, 9, 12 to 17, 19 to 25, 36 to 39 and examples 1 to 7.
The test method comprises the following steps: the pH was measured at 25 ℃.
And (3) testing time: standing at normal temperature, and measuring at 0 month, 1 month, 3 months, 6 months, 12 months, 24 months, and 36 months.
The test results are shown in table 4:
note: "/" indicates no testing was performed.
TABLE 4
The influence of pH value on the stability of the povidone iodine solution is considered by Zhou Qingmin et al in the Chinese dairy industry 2014 No. 1P 46-48 and the influence of pH value on the stability of the povidone iodine solution is considered by the Zhou Qingmin et al, and the stability effect of the povidone iodine solution with the initial pH values of 5.0 and 5.5 is the best, the invention also considers the influence of pH value on the effective iodine stability of the invention in the follow-up process, the betaine addition amount for leading the initial pH value of the povidone iodine solution to be 4.5 to 5.5 is preferred, and the comparative examples 36, 37 and the example 6 also show that the range of the betaine addition amount is preferably 6 to 10kg/100L of the solution, and the initial pH value of the solution is less than 4.5 or more than 5.5.
Comparative example 13 and example 6 show that betaine can stabilize the pH value of povidone-iodine solution, and compared with tween 80 used in comparative examples 8 and 14, polyvinylpyrrolidone used in comparative example 12, chitosan used in comparative example 17, monopotassium phosphate used in comparative example 19, sodium hydroxide solution used in comparative example 20, phosphate buffer solution used in comparative example 21, triethanolamine used in comparative example 22, citric acid-sodium citrate buffer solution used in comparative example 23, and benzyl alcohol used in comparative example 25, the buffering effect is better, so that the pH is reduced more slowly, and the requirement of pH4.5-5.5 can be met within 36 months of shelf life.
The formulations used in comparative examples 38 and 39 were such that the ratio of D-panthenol used was 0.1kg/100L and 0.6kg/100L, respectively, and the pH of comparative example 38 was lowered to 4.5 or less after standing at room temperature for 6 months and comparative example 39 was left standing for 3 months, and the formulations used were such that the range of D-panthenol used was less stable than the pH of the formulations used in examples 1 to 7.
And (4) testing: the invention relates to a moisturizing effect of povidone iodine solution
Povidone iodine solution for testing: the preparation method is selected from comparative examples 9 and 42 and example 6.
Test animals: selecting 40 rabbits with basically the same health condition and growth condition.
Test design and method:
the test groups were divided into 3 groups by the random grouping method, 1 blank group and 10 individuals in each group. Depilating two sides of rabbit back with 8% (mass percent) sodium sulfide, wherein the depilating area is about 15cm2The control group was not coated, the test group was coated with 0.2mL of the povidone-iodine solution prepared in comparative examples 9 and 42 and example 6, and the remaining conditions were the same as those of the control group. Measuring stratum corneum water content of the part by capacitance method skin water content test probe at 15min, 30min, 60min, 90min, and 120 min. The test results are shown in Table 5.
Table 5 usage time and moisture content of skin stratum corneum test results (unit:%) of povidone-iodine solution according to the present invention
| 15min | 30min | 60min | 90min | 120min | |
| Blank control group | 45 | 42 | 46 | 43 | 45 |
| Comparative example 9 | 76 | 63 | 60 | 52 | 50 |
| Comparative example 42 | 57 | 46 | 42 | 40 | 39 |
| Example 6 | 89 | 86 | 80 | 75 | 67 |
As can be seen from Table 5, the iodine tincture of comparative example 42 has a poor moisturizing effect, the moisture content of the iodine tincture is reduced to about 40% at 120min, and the moisture content of the skin stratum corneum of comparative example 9 is also reduced to 50%, while example 6 can keep the moisture content of the skin stratum corneum above 60%, and has good moisturizing effect.
And (5) testing: the invention relates to a moisturizing effect of povidone iodine solution
Test samples: comparative examples 9, 26 to 31, 42, 43; examples 1 to 7.
Test design and method:
30 volunteers were randomly drawn, 15 male and 15 female. The test subjects cleaned the forearms of both hands, sat in a constant humidity environment (25 ℃, RH 43%) for 30min, then used the control of the two side regions of the left and right arms of the test subjects, each region was 3cm × 3cm, and applied 30 μ L samples of the same volume to the test region.
(1) And (3) testing the moisture content of the corresponding experimental part by using a skin moisture tester, respectively repeating the experimental data for 5 times to obtain an average value of each test, recording the data, and calculating to obtain the average skin hydration rate of 30 volunteers at different time intervals of 0h, 5min, 15min, 0.5h, 1h, 3h, 6h, 8h and 12 h.
The skin hydration rate was calculated using the following formula:
the average skin hydration rate was then calculated for 30 subjects at different time intervals, and the results are shown in table 6-1 below:
TABLE 6-1 average skin hydration (%) -of 30 subjects at different time intervals
As can be seen from Table 6-1, the rate of decrease in hydration in comparative example 5min was 10% or more, except for comparative example 9; the comparative example 9 had a 5min hydration rate reduction of 5.0%, but a 3h hydration rate reduction of 57.2%, and the moisturizing performance was not satisfactory, whereas examples 1 to 7 maintained good moisturizing performance for both short and long periods of 3 h.
(2) Survey subjects' experience of use initially and after 3h after application
The test results are shown in Table 6-2.
TABLE 6-2
| Initial | 3h | |
| Comparative example 9 | Has slight cool feeling and no other special feeling | The applied part is dry and the skin feels tight |
| Comparative example 26 | Can be uniformly coated and distributed, and has good dispersibility | The applied part is dry and the skin feels tight |
| Comparative example 27 | Can be uniformly coated and distributed, and has good dispersibility | Skin moisturization without other feeling |
| Comparative example 28 | Can be uniformly coated and distributed, and has good dispersibility | Skin moisturization without other feeling |
| Comparative example 29 | Can be uniformly coated and distributed, and has good dispersibility | Skin moisturization without other feeling |
| Comparative example 30 | Can be uniformly coated and distributed, and has good dispersibility | Skin moisturization without other feeling |
| Comparative example 31 | Can be uniformThe coating is distributed and the dispersibility is good | Skin moisturization without other feeling |
| Comparative example 42 | Has light and cool feeling and can be volatilized quickly | The applied part is dry and the skin feels tight |
| Comparative example 43 | Can be uniformly coated and distributed, and has good dispersibility | Skin moisturization without other feeling |
| Example 1 | Can be uniformly coated and distributed, and has good dispersibility | Skin moisturization without other feeling |
| Example 2 | Can be uniformly coated and distributed, and has good dispersibility | Skin moisturization without other feeling |
| Example 3 | Can be uniformly coated and distributed, and has good dispersibility | Skin moisturization without other feeling |
| Example 4 | Can be uniformly coated and distributed, and has good dispersibility | Skin moisturization without other feeling |
| Example 5 | Can be uniformly coated and distributed, and has good dispersibility | Skin moisturization without other feeling |
| Example 6 | Can be uniformly coated and distributed, and has good dispersibility | Skin moisturization without other feeling |
| Example 7 | Can be uniformly coated and distributed, and has good dispersibility | Skin moisturization without other feeling |
As can be seen from Table 6-2, comparative examples 9, 26, and 42 had dry skin and a tight feeling after 3 hours; comparative examples 27 to 31, 43 and examples 1 to 7 were kept in a wet state.
And (6) test six: the invention relates to a stability test of effective iodine content of accelerated test of povidone iodine solution
Povidone iodine solution for testing: prepared by the method of comparative examples 12, 34-37 and examples 1-7.
Selecting a proper packaging container (a bottle made of PE material is adopted in the test), carrying out a stability acceleration test according to GB/T38499-.
The test results are shown in table 7:
table 7 stability of available iodine content of povidone-iodine solution under accelerated conditions (unit:%)
It can be seen from table 7 that the reduction rate of the povidone-iodine content of comparative examples 12, 34 to 37 after 9 months is 10% or more under the accelerated test conditions, the stability is not as stable as that of examples 1 to 7, and the content of comparative example 35 exceeds the theoretical value ± 10% at 0 month, 1 month and comparative examples 12, 36 and 37 after accelerated to 9 months, the content of comparative example 34 is critical at 9 months, and the content of examples 1 to 7 is within ± 10% of the theoretical value, so that the effective period of examples 1 to 7 can be predicted to 36 months according to the disinfectant stability evaluation method.
It can be seen from comparative examples 36 and 37 and examples 1 to 7 that the initial pH values of examples 36 and 37 are 4.23 and 5.59, which are in the range of pH3.5 to 6.5, but the effective iodine stability is inferior to that of other examples having pH values of 4.5 to 5.5, so that the formulation ratio in this range is preferable in the present invention.
Test seven: the invention relates to effective iodine content and stability of povidone iodine solution
Povidone iodine solution for testing: the formulations were prepared by the methods of examples 1-7.
(1) Effective iodine test conditions: the detection is carried out according to the related requirements of povidone iodine solution in the pharmacopoeia of the people's republic of China 2015 edition, and the specific method is as follows: about 1g of the product was weighed out precisely, placed in a beaker, added with 120ml of water, stirred to dissolve, and titrated with sodium thiosulfate titrant (0.1mol/L) by potentiometric titration. Each 1mL of sodium thiosulfate titration solution (0.1mol/L) corresponds to 12.69mg of I.
(2) And (3) testing time: 0. measurements were performed for 1, 3, 6, 9, 12, 18, 24, 36 months, respectively.
The test results are shown in table 8:
table 8 effective iodine stability for povidone-iodine solutions
| Available iodine (%) | 0 month | 1 month | 3 months old | 6 months old | 9 months old | 12 months old | 18 months old | 24 months | 36 months old |
| Example 1 | 0.51 | 0.50 | 0.51 | 0.50 | 0.51 | 0.49 | 0.48 | 0.49 | 0.49 |
| Example 2 | 0.60 | 0.60 | 0.59 | 0.59 | 0.60 | 0.60 | 0.59 | 0.58 | 0.59 |
| Example 3 | 0.74 | 0.73 | 0.72 | 0.72 | 0.71 | 0.70 | 0.71 | 0.69 | 0.69 |
| Example 4 | 0.82 | 0.80 | 0.81 | 0.81 | 0.80 | 0.79 | 0.79 | 0.78 | 0.78 |
| Example 5 | 0.93 | 0.93 | 0.92 | 0.91 | 0.91 | 0.91 | 0.90 | 0.89 | 0.89 |
| Example 6 | 1.05 | 1.04 | 1.04 | 1.03 | 1.03 | 1.02 | 1.00 | 1.01 | 1.00 |
| Example 7 | 1.02 | 1.01 | 1.02 | 1.00 | 1.01 | 1.00 | 0.99 | 0.99 | 0.98 |
As can be seen from Table 8, examples 1-7 all achieved a stable effective iodine content within + -10% of theoretical values over a 36 month shelf life.
And (eight) test: the sterilization test effect of the povidone-iodine solution provided by the invention
Since the invention is applied to disinfection of human skin and skin mucous membrane, the test investigates whether the povidone-iodine solution can be quickly sterilized.
Povidone iodine solution for test was prepared by the methods of examples 1, 6 and 7.
Test strains: escherichia coli, Staphylococcus aureus, Salmonella, Pseudomonas aeruginosa, and Candida albicans were purchased from the microorganism culture Collection.
Culture medium: tryptone soy agar medium (TSA): tryptone 1.5%, soybean peptone 0.5%, sodium chloride 0.5%, agar 1.6%, water 1L, pH7.2 + -0.2, and autoclaving at 121 deg.C for 20 min.
Neutralizing agent: 1.0% sodium thiosulfate + 0.2% tween-80 +1000ml pbs.
Organic interferents: 3% bovine serum albumin.
Main instruments, tools: a steam sterilization pot, a superclean bench, a constant temperature incubator, a culture dish, a glass bottle, a measuring cylinder and a liquid-transfering gun.
The test method comprises the following steps:
according to the quantitative sterilization test of bacterial suspension in the technical Specification for disinfection, the bacterial concentration is 108Adding cfu/ml test strain 0.5ml into a small test tube, adding 0.5ml organic interference substance, mixing, adding 4.0ml sample to be tested, mixing, and acting for 0.5min, 1.0min, and 1.5min respectively. Adding 0.5ml of the mixture into 4.5ml of a neutralizing agent, uniformly mixing, and acting for 10 min. Adding 1.0ml of the culture dish into a sterilized culture dish, adding 15-20 ml of culture medium, shaking up, and carrying out inverted culture in a constant-temperature incubator at 37 ℃ for 48 hours.
The test steps are as follows:
(1) preparing a proper amount of tryptone soy agar medium (TSA), normal saline, a neutralizing agent and purified water, placing the culture dishes and the tips of the culture dishes in a required number in a sterilization pot, sterilizing for 20min at 121 ℃, taking out and placing on a super-clean workbench for later use (placing the culture medium in a water bath at 40-45 ℃);
(2) preparing test bacterial suspension with concentration of 1 × 108cfu/ml～5×108cfu/ml；
(3) Taking a sterile test tube for a disinfection test, firstly adding 0.5ml of test bacterial suspension, then adding 0.5ml of organic interference substance, uniformly mixing, placing in a water bath at 20 ℃ for 5min, sucking 4.0ml of disinfectant with the concentration by using a sterile straw, injecting into the sterile test tube, rapidly mixing uniformly and immediately timing;
(4) respectively sucking 0.5ml of test bacterium and disinfectant mixed solution into 4.5ml of sterilized neutralizer after the test bacterium and the disinfectant interact for each preset time, and uniformly mixing;
(5) adding a neutralizing agent into the mixed solution of the test bacteria and the disinfectant for 10min, respectively sucking 1.0ml of sample solution, adding the sample solution into a sterilized culture dish, adding 15-20 ml of culture medium, shaking up, and inversely culturing in a constant-temperature incubator at 37 ℃ for 48 h;
(6) meanwhile, the diluent is used for replacing disinfectant, and a parallel test is carried out to be used as a positive control;
(7) at the same time, the diluent + neutralizer + medium were used for parallel experiments as negative controls.
The test results are shown in tables 9-1 and 9-2:
TABLE 9-1 Positive control colony number results
| Bacterial species name | Total number of colonies in positive control group |
| Escherichia coli | 3.4×108cfu/ml |
| Staphylococcus aureus | 2.2×108cfu/ml |
| Salmonella | 2.7×108cfu/ml |
| Pseudomonas aeruginosa | 1.8×108cfu/ml |
| Candida albicans | 2.5×108cfu/ml |
TABLE 9-2 Sterilization test results of samples to be tested
As can be seen from tables 9-1 and 9-2, examples 1, 6 and 7 all have good effects on killing Escherichia coli, Staphylococcus aureus, Salmonella, Pseudomonas aeruginosa and Candida albicans.
Test nine: the povidone iodine solution has the effect of no yellow stain
Test samples: comparative examples 9, 26, 42, 43; examples 6 and 7.
Test materials:
(1) the same PVC plastic floor is used in the operating room, the specification is 10cm multiplied by 10cm, and each group comprises 3 pieces.
(2) Laboratory glass petri dishes, with a specification diameter of 150 mm.
(3) Silk with a specification of 10cm multiplied by 10cm is divided into 3 pieces.
(4) Pure cotton cloth with a specification of 10cm × 10cm, 3 pieces each.
(5) Blending, the specification is 10cm multiplied by 10cm, and each group comprises 3 pieces.
And (3) experimental design: 3mL of the test material is measured and dripped on the surface of the test material, the test material is placed for 10min, 1h, 4h, 8h, 1d, 7d, 14d, 30d and 90d, the PVC plastic floor material is wiped by clean water, a laboratory glass culture dish is wiped by a dry paper towel, and the textile fabric is rubbed by the clean water and normally cleaned until the color of the test material is unchanged.
Evaluation method:
yellow dyeing: a yellow color visible to the naked eye.
The test results are shown in Table 10.
Note: "/" indicates that the experiment was not continued.
Watch 10
FIGS. 1-1 to 1-3 are graphs of the behavior of laboratory glass petri dishes after smearing comparative example 26, example 6 initially, 0.5h and 24 h.
From Table 10, it can be seen that comparative examples 9, 26, 42, 43 are more difficult to wipe or clean and more severe in yellowing in different materials (same PVC plastic floor in operating room, glass petri dish in laboratory, silk, pure cotton cloth, blended) with time; and the examples 6 and 7 can be wiped or cleaned without yellow stain.
It can be seen from fig. 1-1 to fig. 1-3 that on a glass culture dish, the liquid surface is preliminarily shown to be dry and dry after 0.5h in the comparative example 26, the film which is dry and thoroughly adhered to the glass surface after 24h is placed, and the hand cannot be scratched for a long time, but the example 6 is still in a wet liquid state and can be easily wiped off. The property maps of the comparative example 9 and the comparative example 26 are similar, the property maps of the comparative example 43 and the examples 6 and 7 are similar, the effects are also similar, and the test is not listed in the chart again.
Test ten: the invention relates to one-time complete skin irritation test condition of povidone iodine solution
Test samples: comparative examples 2, 6, 8, 42, 43; examples 2, 3 and 6.
Test animals: common New Zealand rabbits, 21, 3 per group, body weight range: 2.0-2.2 kg.
The test method comprises the following steps: disinfection Specification 2002 edition, second section 2.3.3.
The test conditions are as follows: the ambient temperature is 20-26 ℃, and the relative humidity is 40-70%.
The test steps are as follows: hairs on both sides of the spine of the rabbit were shaved off before the test. The hair removal range is about 3cm × 3cm for each of the left and right sides. The next day, 0.5mL of the test substance was directly applied to one side of the skin, covered with a non-irritating plastic film, and fixed with a non-irritating adhesive tape. The other side of the skin served as a blank control. The application time is 4h by adopting a sealing test. After the experiment, the residual test substance was removed with warm water.
And (4) evaluating the results:
and respectively observing the skin reaction results of the tested part at 1h, 24h and 48h after the test substances are removed, and scoring the skin reaction according to a skin irritation reaction scoring table. And judging the skin irritation strength according to a skin irritation strength grading standard table according to the highest integral mean value of each observation point of 1h, 24h and 48 h.
The test results are shown in Table 11:
TABLE 11
From table 11, comparative examples 2, 6, 8, 42, 43; the results of the one-time complete skin irritation test of examples 2, 3 and 6 are non-irritant, and the subsequent examination and comparison of the one-time damaged skin irritation test are carried out.
Test eleven: the invention relates to one-time damaged skin irritation test condition of povidone iodine solution
Test samples: comparative examples 2, 6, 8, 42, 43; examples 2, 3 and 6.
Test animals: common New Zealand rabbits, 21, 3 per group, body weight range: 2.0-2.2 kg.
Test methods and evaluation: disinfection Specification 2002 edition, second section 2.3.3.
The test conditions are as follows: the ambient temperature is 20-26 ℃, and the relative humidity is 40-70%.
The test steps are as follows: 24h before the test, the hair on both sides of the spine of the rabbit is shaved off. The hair removal range is about 3cm × 3cm for each of the left and right sides. Before applying on the test object, cleaning and sterilizing the exposed skin on the unhaired skin of 2.5cm × 2.5cm with 75% alcohol, scratching a 'well' -shaped damaged wound in the skin area with an injection needle after the alcohol is volatilized, and infecting the damaged skin area with poison. Note that the skin is damaged only to the epidermis, and the dermis is not damaged.
0.5ml of the test substance was applied to one side of the skin. Then covering with a layer of non-irritating plastic film, and fixing with non-irritating adhesive plaster. The other side of the skin served as a blank control. The application time is 4h by adopting a sealing test. After the test was completed, the residual test substance was removed with water.
And (4) evaluating the results: and respectively observing the skin reaction results of the tested part at 1h, 24h and 48h after the test substances are removed, and scoring the skin reaction according to a skin irritation reaction scoring table. And judging the skin irritation strength according to a skin irritation strength grading standard table according to the highest integral mean value of each observation point of 1h, 24h and 48 h.
TABLE 12-1 skin irritation response Scoring standards
TABLE 12-2 skin irritation Strength grading
The test results are shown in tables 12-3:
tables 12 to 3
From tables 12-3, it can be seen that comparative examples 2, 6, 8, 42, 43 all exhibited varying degrees of irritation in the single insult skin irritation test, while examples 2, 3, 6 were non-irritating.
Test twelve: the invention relates to acute oral toxicity test conditions of povidone iodine solution
Test samples: example 6.
Animal species strains: SPF grade KM mice; 10 males and 10 females, weight range 18-22 g.
The detection method comprises the following steps: disinfection Specification 2002 edition, second section 2.3.1.
Dose level: according to the requirements of the method, a one-time dose limiting method (namely, a 5000mg/kg BW body weight dose is orally taken by 20 animals) is adopted.
The test steps are as follows: prior to the test, the experimental animals were fasted overnight without restriction of water. During the test, the animal weight is weighed, randomly grouped, and the gavage is performed for 1 time through mouth, the gavage amount is 0.2ml/10g of the animal weight each time, the animal is continuously fasted for 3 hours after the gavage, and then the animal is fed with normal diet. After the infection, each animal was individually and thoroughly recorded, and the experimental animals were observed for signs of intoxication and death, and thereafter, carefully examined once a day, and the body weights were measured at the administration of D0, D7 and D14. The observation period was 14 d.
And (4) evaluating the results: for evaluation, LD50 was calculated from the data and judged according to the oral toxicity classification table.
The test results are shown in Table 13:
watch 13
Note: all tested animals did not show obvious toxic symptoms and death within the 14-day observation period.
As is clear from Table 13, the acute oral toxicity LD50 of the test substance on SPF-grade KM mice is more than 5000mg/kg BW under the test conditions, and the test substance is practically nontoxic.
Test thirteen: the invention relates to acute eye irritation test condition of povidone-iodine solution
Firstly, a test sample: comparative examples 6, 42, 43, example 6.
II, testing animals:
1. ordinary grade animal house, the license number is used to the experimental animals: SYXK (Yue) 2016-.
2. Animal species strains: common grade New Zealand rabbits; 12 females; body weight range: 2.0-2.2 kg; animal certification number: 44007600007442.
3. animal sources: the experimental animal is provided by a Dongxinghua experimental animal farm (the experimental animal production license number: SCXK (Yue) 2019-.
Thirdly, the method comprises the following steps:
the detection method comprises the following steps: disinfection Specification 2002 edition, second section 2.3.4.
Detection conditions are as follows: the ambient temperature is 22-25 ℃, and the relative humidity is 40-70%.
Fourthly, testing steps:
both eyes of the experimental animals were routinely examined 24h prior to the experiment. In the test, 0.1mL of the test object is dripped into the conjunctival sac, the eye is passively closed for 4s to prevent the test sample from being lost, and the test sample is washed by normal saline after 30 s. The other side was normal control with normal saline. The eyes were examined at 1h, 24h, 48h, 72h, 7d, 14d after the end of the test, and 14d was observed to terminate the test. Changes in the cornea and iris were examined with 2% sodium fluorescein solution during observation. The score of the ocular irritation response was recorded at each examination according to the ocular damage score standard.
Fifthly, evaluating results:
the acute irritation responses of the cornea, iris and conjunctiva of the rabbit eyes were scored and the mean score for each animal was calculated for each animal in terms of corneal damage, iris damage, conjunctival hyperemia and conjunctival edema at three different observation times (24h, 48h and 72 h). The average scores and recovery time of cornea, iris and conjunctival congestion and edema of the animal eyes are respectively used for judging the stimulation intensity of the test object to the eyes according to the grading standard of eye stimulation response. If no irritation response occurs within 72 hours, or on day 7 or 14, the eye irritation response is completely restored, and the test can be terminated early.
The test results are shown in Table 14:
note: "-" indicates no test was performed and the average integration was the sum of the scores for 24, 48, 72h for each group of animals divided by the number of observations 3.
TABLE 14
It can be seen from table 14 that comparative examples 6, 42, 43 are more irritating than example 6.
Fourteen experiments: the invention relates to the coagulation test condition of povidone-iodine solution
Test samples: comparative examples 6, 42, 43, examples 1-7.
Blood coagulation test: taking a glass test tube with the diameter of 8mm, and respectively adding 0.05mg of the test sample and 0.95ml of deionized water into each tube, and then adding 1ml of calcium chloride solution; after shaking uniformly, 1ml of anticoagulated plasma was added into each tube at the same time, and the mixture was shaken gently and mixed uniformly, and then placed into a 37 ℃ water bath pot for observation, and from the time when the anticoagulated plasma was added, the time was counted until the mixture was coagulated, and the counting was stopped, and the results are shown in Table 15.
Watch 15
| Group of | Blood coagulation time (min) |
| Normal blood coagulation | 9.4 |
| Comparative example 6 | 3.6 |
| Comparative example 31 | 8.2 |
| Comparative example 32 | 7.4 |
| Example 1 | 3.5 |
| Example 2 | 3.2 |
| Example 3 | 3.4 |
| Example 4 | 3.2 |
| Example 5 | 3.3 |
| Example 6 | 3.1 |
| Example 7 | 3.5 |
As can be seen from Table 15, the blood coagulation effects of comparative examples 42 and 43 were inferior to those of comparative example 6 and examples 1 to 7, and the blood coagulation times of comparative example 6 and examples 1 to 7 were comparable.
Test fifteen: the invention relates to a situation that povidone iodine solution promotes wound healing
SD male rats weighing 250-270g each were used as experimental animals, and 20 animals per group were used. On one side of the spine of the back of the rat, white hair was cut off, and under anesthesia, an incision with a wound size of 1cm x 1cm and a depth of 0.2cm was made with a surgical knife. Observed at 2, 5, 8, 12, 16d post-injury, respectively. The povidone-iodine solutions obtained in examples 1 to 7 were applied to the wound once a day, morning and evening, respectively. The wound healing rate was calculated at each sampling time point. The area of the wound was measured using standard clear grid films and the wound healing rate was calculated as (pre-treatment area-post-treatment area)/pre-treatment area 100%.
The test results are shown in Table 16:
TABLE 16
| Time of sampling | 2d | 5d | 8d | 12d | 16d |
| Example 1 | 15.2 | 40.6 | 85.2 | 97.2 | 98.4 |
| Example 2 | 16.2 | 41.3 | 86.4 | 96.4 | 99.3 |
| Example 3 | 15.5 | 40.7 | 84.3 | 95.9 | 98.1 |
| Example 4 | 15.9 | 41.4 | 82.5 | 96.5 | 98.3 |
| Example 5 | 15.4 | 41.6 | 84.3 | 95.7 | 99.4 |
| Example 6 | 16.3 | 40.8 | 85.7 | 96.2 | 98.5 |
| Example 7 | 16.1 | 40.5 | 86.4 | 96.6 | 99.1 |
From table 16, it can be seen that the povidone-iodine solution of the present invention can heal up to more than 95% at 12d and heal up substantially at 16d, which indicates that the povidone-iodine solution of the present invention has a good effect on promoting wound healing.
Test sixteen: the effect of the povidone iodine solution on treating the onychomycosis
Povidone iodine solution for testing: comparative examples 24, 25, 38, 39, examples 1, 6, 7.
70 patients who are positively diagnosed by fungus through microscopic examination of a diseased nail specimen are selected, randomly divided into 7 groups, 10 patients in each group are smeared with the povidone iodine solution twice a day in the morning and at night, and manual nail repair is combined. The treatment lasts for 2-3 months.
And (3) judging the curative effect:
firstly, curing: the normal new nail grows out completely, and the nail specimen is negative in fungus by microscopic examination;
secondly, effect is displayed: the growth of new nail is more than 50%, and the nail specimen is negative to fungus by microscopic examination;
③ effective: the new nail grows, and the nail specimen is negative or positive in fungus by microscopic examination;
fourthly, invalidation: no new nail grows, and the nail specimen is positive in fungus by microscopic examination.
Effective rate (%) - (number of effective persons + number of effective persons)/total number of persons × 100%
The test results are shown in Table 17:
TABLE 17
| Number of effective people | Number of effective persons | Number of invalid persons | Effective rate% | |
| Comparative example 24 | 1 | 3 | 6 | 40 |
| Comparative example 25 | 1 | 4 | 5 | 50 |
| Comparative example 38 | 1 | 2 | 7 | 30 |
| Comparative example 39 | 1 | 3 | 6 | 40 |
| Example 1 | 2 | 4 | 4 | 60 |
| Example 6 | 3 | 6 | 1 | 90 |
| Example 7 | 3 | 5 | 2 | 80 |
It can be seen from Table 17 that the effective rates of examples 1, 6 and 7 are higher than those of comparative examples 24, 25, 38 and 39, and the number of significant persons of examples 1, 6 and 7 is also higher than those of comparative examples 24, 25, 38 and 39, and thus it can be seen that in the case of the equivalent effective iodine content, the effect of comparative example 24 is not as good as that of example 6 because D-panthenol is not added, benzyl alcohol is added to comparative example 25, and 0.1kg/100L of D-panthenol is added to comparative example 38, while the effect of comparative example 39 is 0.6kg/100L of D-panthenol, the viscosity is decreased because more D-panthenol is added, the adhesion and the pH thereof are somewhat affected, and no better effect is exhibited than that of example 6.
Seventeen tests: the invention relates to the effect of povidone iodine solution on treating incised wound and scratch
After a woman is accidentally cut by a knife, firstly, clean water is used for washing dust on the surface, then, a medical cotton swab is used for sucking water, then, one drop of the povidone iodine solution for human use, which is prepared in the embodiment 7, is immediately dropped on the wound, the povidone iodine solution for human use is uniformly smeared by the medical cotton swab, after smearing, the wound is rapidly stopped bleeding, the wound is scabbed after hours, then, the povidone iodine solution for human use is smeared for 3-4 times every day, the wound is completely healed after one week, no scar is left, and the wound disappears after three weeks and is intact as before. As shown in fig. 2-1 through 2-6.
After the nail of a baby of 6 months old scratches the face, a drop of the povidone iodine solution prepared in example 5 is applied uniformly to the finger, and the wound is found to be completely recovered as before after two days without scar. As shown in fig. 3-1 through 3-2.
The preferred embodiments of the present invention have been described in detail, however, the present invention is not limited to the specific details of the above embodiments, and various simple modifications may be made to the technical solution of the present invention within the technical idea of the present invention, and these simple modifications are within the protective scope of the present invention.
It should be noted that the various features described in the above embodiments may be combined in any suitable manner without departing from the scope of the invention. The invention is not described in detail in order to avoid unnecessary repetition.
Claims (10)
1. The povidone-iodine solution for human use is characterized by being prepared from the following components: 5-10kg of povidone iodine, 0.5-1.0kg of potassium iodide, 6-10kg of betaine, 0.2-0.5kg of D-panthenol, 30-65kg of water and the balance of glycerol are prepared into a solution with the total amount of 100L.
2. The povidone-iodine solution for human use as claimed in claim 1, wherein: the povidone iodine is formed by forming a micro cavity-coating carrier by povidone PVP and complexing iodine I ions in a cavity of the microcapsule.
3. The povidone-iodine solution for human use as claimed in claim 1, wherein: the potassium iodide is a pharmaceutical grade auxiliary material, and the content is more than or equal to 99.0 wt% of a dry product.
4. The povidone-iodine solution for human use as claimed in claim 1, wherein: the weight part ratio of the povidone iodine to the potassium iodide is 10: 1.
5. the povidone-iodine solution for human use as claimed in claim 1, wherein: the glycerol is a pharmaceutical grade auxiliary material and contains C3H8O3≥95.0wt％。
6. The povidone-iodine solution for human use as claimed in claim 1, wherein: the content of betaine is C5H11NO2Calculated by more than or equal to 98.0wt percent.
7. The povidone-iodine solution for human use as claimed in claim 1, wherein: the content of D-panthenol is more than or equal to 98.0 wt% on a dry basis.
8. The povidone-iodine solution for human use as claimed in claim 1, wherein: the povidone iodine for human use has the density of 1.17g/mL-1.28g/mL and the pH of 4.5-5.5.
9. A preparation method of povidone iodine solution for human use is characterized by adopting the following components: 5-10kg of povidone iodine, 0.5-1.0kg of potassium iodide, 6-10kg of betaine, 0.2-0.5kg of D-panthenol, 30-65kg of water and the balance of glycerol are prepared into solution with the total amount of 100L; the preparation steps are as follows:
the method comprises the following steps: weighing water with a prescribed amount into a corrosion-resistant reaction kettle, adding potassium iodide with a prescribed amount, starting the reaction kettle, adjusting the rotation speed of a stirring paddle to 1200r/h, adding betaine with a prescribed amount after complete dissolution, and stirring and dissolving to form a body system 1;
step two: adding the D-panthenol with the prescription amount into the system 1, uniformly stirring, adding the povidone iodine with the prescription amount, and stirring for 30 minutes to form a system 2;
step three: adding the rest of glycerol into the system 2 while stirring, and stirring for 20min after completely adding to obtain povidone iodine solution for human use.
10. The method of claim 9, wherein the corrosion resistant reaction vessel and the stirring blade are made of corrosion resistant materials.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1481812A (en) * | 2003-07-23 | 2004-03-17 | 南京大学 | Spray formulation of providone iodine |
| CN110025632A (en) * | 2019-05-20 | 2019-07-19 | 中山万汉制药有限公司 | A kind of povidone iodine composition and preparation method thereof and external preparation |
| US20190381187A1 (en) * | 2016-12-29 | 2019-12-19 | Cenyx Biotech Inc. | Ceria nanocomposite for biomedical treatment and pharmaceutical composition containing same |
| CN112680295A (en) * | 2020-12-25 | 2021-04-20 | 上海兰轩新黛日用化学品科技有限公司 | Efficient sterilization concentrated detergent containing povidone iodine and preparation method thereof |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1481812A (en) * | 2003-07-23 | 2004-03-17 | 南京大学 | Spray formulation of providone iodine |
| US20190381187A1 (en) * | 2016-12-29 | 2019-12-19 | Cenyx Biotech Inc. | Ceria nanocomposite for biomedical treatment and pharmaceutical composition containing same |
| CN110025632A (en) * | 2019-05-20 | 2019-07-19 | 中山万汉制药有限公司 | A kind of povidone iodine composition and preparation method thereof and external preparation |
| CN112680295A (en) * | 2020-12-25 | 2021-04-20 | 上海兰轩新黛日用化学品科技有限公司 | Efficient sterilization concentrated detergent containing povidone iodine and preparation method thereof |
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