CN111001010B - External eye operation flushing fluid and preparation method thereof - Google Patents
External eye operation flushing fluid and preparation method thereof Download PDFInfo
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- CN111001010B CN111001010B CN201911384155.9A CN201911384155A CN111001010B CN 111001010 B CN111001010 B CN 111001010B CN 201911384155 A CN201911384155 A CN 201911384155A CN 111001010 B CN111001010 B CN 111001010B
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- 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
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
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- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
- A61K31/728—Hyaluronic acid
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- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/734—Alginic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/48—Reproductive organs
- A61K35/50—Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/02—Local antiseptics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
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- 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
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
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- 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
- A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
Abstract
The invention discloses an external eye surgical flushing fluid and a preparation method thereof, belonging to the technical field of surgical flushing fluids, and comprising the following components: NaCl, KCL, CaCl 2 ·2H 2 O、MgCl 2 ·6H 2 O、C 2 H 3 NaO 2 ·3H 2 O、C 6 H 5 Na 3 O 7 ·2H 2 O, cocamidopropyl betaine, digitonin, esculetin, amnion extract, trehalose and hyaluronic acid. Through the combined application of the components, the grease in an operation area, tissue scraps generated in the operation and the like can be more easily cleaned, the cleanliness of the operation area is improved, the number of the bacteria in the conjunctival sac is reduced, the tissue repair is promoted, the postoperative inflammatory reaction is relieved, and the discomfort such as eye edema, hyperemia, dryness and the like is relieved. Meanwhile, the solutions have small irritation, no toxic or side effect and low cost, and are suitable for wide clinical application.
Description
Technical Field
The invention relates to the technical field of surgical flushing fluid, and particularly relates to external eye surgical flushing fluid and a preparation method thereof.
Background
Ophthalmic surgery typically requires the application of a physiological irrigation solution to protect and maintain the physiological integrity of the intraocular tissue. There are many external eye surgery operations that generally require an irrigating solution, and corneal refractive surgery, strabismus surgery, lamellar corneal transplantation surgery, pterygium surgery, and the like are common, and among them, corneal refractive surgery is most used. Ophthalmic refractive surgery refers to surgery to change the existing refractive state of the eye. The laser cornea refractive surgery is the most widely used clinically, and the aim of changing the refractive state is achieved by cutting the cornea tissue with laser or manufacturing a micro lens with laser and taking out the micro lens. The laser cornea refractive surgery has the action target of the cornea, and the main targets are the corneal superficial layer (superficial layer surgery) and the corneal stroma (lamellar surgery). Most of patients who undergo laser cornea refractive surgery are young, oil secretion is vigorous, and oil and fat washing during surgery is difficult, so that the visual field definition of the surgery is influenced. The incidence of haze after superficial laser corneal refractive surgery is high.
The surgical irrigating solution is primarily in a physiological fluid carrier which is an aqueous solution including physiological electrolytes, such as saline or lactated ringer's solution. However, the solutions are not optimal because of the problems of unclear operative field caused by the fact that the oil and fat are not easy to flush in the operation, high quantity of postoperative conjunctival sac bacterial flora, heavy inflammatory reaction, unfavorable cornea repair, tear film stabilization and the like. The eye tissues can be well protected by adding different agents such as electrolyte, a buffer for regulation, glutathione and/or energy such as dextrose into other aqueous solutions, or adding agent components for resisting inflammation, easing pain, dispersing pupil and reducing blood pressure, but the problem that the oil and fat are not easy to wash in the operation exists. And each of these methods has limitations. These limitations may include corneal and conjunctival poisoning, tissue damage, eye perforation, optic nerve damage, retinal middle artery and or vein occlusion, immediate retinal drug poisoning, and systemic side effects.
Disclosure of Invention
The invention provides an external eye operation flushing fluid and a preparation method thereof, and solves the problems of unclear operation field, high postoperative conjunctival sac flora number, heavy inflammatory reaction, unfavorable cornea repair and tear film stability caused by the fact that the oil in the operation is difficult to flush in the existing external eye operation flushing fluid.
In order to solve the technical problem, the technical scheme of the invention is realized as follows:
an external eye operation washing liquid is prepared by taking a balanced salt solution (mainly containing electrolytes and water and providing a proper pH value and osmotic pressure) as a basic solvent, adding cocamidopropyl betaine, digitonin, esculetin, trehalose, an amniotic membrane extract and hyaluronic acid, and adjusting the pH value and the osmotic pressure to be close to those of tears, wherein the pH value is 6.5-7.5, and the osmotic pressure is: 295 to 309 mOsm/L.
Comprises the following components by mass percent: NaCl 0.64%, KCL 0.075%, CaCl 2 ·2H 2 O0.048％、MgCl2·6H 2 0.03 percent of O, 0.39 percent of C2H3NaO 2.3H 2O 0.39, 0.17 percent of C6H5Na3O 7.2H2O 0.17, 0.0005 to 0.01 percent of cocamidopropyl betaine, 0.001 to 0.006 percent of digitonin, 0.005 to 0.03 percent of esculetin, 0.01 to 1 percent of amnion extracting solution, 0.01 to 1 percent of trehalose, 0.01 to 2 percent of hyaluronic acid and the balance of purified water.
The washing liquid for the external eye surgery comprises the following components in percentage by mass: NaCl 0.64%, KCL 0.075%, CaCl2 & 2H2O 0.048.048%, MgCl2 & 6H 2 O 0.03％、C2H3NaO2·3H2O 0.39％、C 6 H 5 Na 3 O 7 ·2H 2 0.17 percent of O, 0.001 to 0.005 percent of cocamidopropyl betaine, 0.004 to 0.006 percent of digitonin, 0.01 to 0.03 percent of esculetin, 0.5 to 1 percent of amnion extract, 0.5 to 1 percent of trehalose, 0.5 to 1 percent of hyaluronic acid and the balance of water.
Preferably, the preparation method of the amnion extract comprises the following steps: taking placenta delivered by caesarean section, cleaning, separating amnion, grinding by liquid nitrogen, adding medical normal saline according to the weight-volume ratio of 1: 5-10, and homogenizing to obtain homogenate; standing the homogenate at 0-4 ℃ for 1-7 days, heating at 100-120 ℃ for 30-60 minutes, and filtering to obtain a filtrate; adjusting the pH value of the filtrate to 3, standing, filtering, and taking the filtrate; adjusting the pH value of the filtrate to 7.2, filtering with a 0.20-0.22um filter membrane under aseptic conditions, collecting the filtrate, namely the placenta tissue extract, and storing at 0-4 ℃ for later use.
Wherein, preferably, the purified water is drinking water obtained by distillation, ion exchange or reverse osmosis.
The invention also provides a preparation method of the external eye surgical irrigating solution, which comprises the following steps:
the method comprises the following steps: taking NaCl, KCL and CaCl 2 ·2H 2 O、MgCl 2 ·6H 2 O、C 2 H 3 NaO 2 ·3H 2 O and C 6 H 5 Na 3 O 7 ·2H 2 Adding O into the purified water, then adding into a stirring device after disinfection treatment, and dissolving and stirring the mixed materials uniformly;
step three: adjusting pH to 7.4-7.6, and osmotic pressure to 300mOsm/L to obtain balanced salt solution;
step four: adding digitonin, esculetin, hyaluronic acid and trehalose into the balanced salt solution, adding into a sterilized stirring device, and dissolving and stirring the mixture uniformly;
step five: adding cocamidopropyl betaine, slowly stirring uniformly, adjusting the pH value to 7.2, and adjusting the osmotic pressure: 300mOsm/L, heating at 100-120 ℃ for 30-60 minutes, cooling to room temperature, placing in a 4-degree refrigerator, and standing for 30 min;
step six: adding amnion extract, filtering with 0.20-0.22um filter membrane under aseptic condition, and sealing and storing the filtrate at 0-4 deg.C.
The preparation method of the invention adopts NaOH or HCl to adjust the pH value.
The surfactant cocoamidopropyl betaine is added into the balanced salt solution, is a zwitterionic surfactant, has excellent stability under acidic and alkaline conditions, respectively presents positive and negative ion, has small irritation, is easy to dissolve in water, is stable to acid and alkali, has strong detergency, and has excellent bactericidal property, antistatic property, hard water resistance and biodegradability. The cleanness of the operative field can be obviously improved after the component is added.
The invention adds digitonin and esculetin into balanced salt solution. Digitonin and esculetin are vasoactive drugs, and digitonin activates Retinal Pigment Epithelium (RPE) cytochrome epithelial enzyme to increase nutrient delivery, thereby promoting photoreceptor cell function recovery; digitalis glycosides can increase ciliary muscle contraction and increase the accommodative function. Esculetin is a vasoactive component, reduces vascular resistance, increases ciliary muscle blood flow, and improves transport of nutrients and transport of metabolites. The combination of the two can improve the regulation function of ciliary muscle and protect retina, and has been used for treating various types of asthenopia and fundus macular degeneration. In addition, digitonin can inhibit Na + -K + -ATP enzyme activity of cell membrane, increase calcium ion influx of muscle cell, and decrease sodium ion efflux of cornea, so as to stabilize water content of cornea and reduce tear osmotic pressure. Can adhere to the surface of corneal epithelial layer for a long time. The glucoside in the two chemical components can reduce surface tension, stabilize tear film, prolong tear film rupture time, keep cornea moist, and maintain normal growth of epithelial cells.
The invention adds amnion extract into balanced salt solution, amnion contains extensive extracellular matrix, including type I, III, IV, V collagen, laminin and various cell factors such as Hepatocyte Growth Factor (HGF), Epidermal Growth Factor (EGF), basic fibroblast growth factor (bFGF), Transforming Growth Factor (TGF), etc. The amnion extract has the following tissue biological activities: (1) and the immunogenicity is low. The amnion extracting solution has good stability and extremely low immunogenicity, and can hardly cause immunological rejection of organisms. (2) Promoting the growth of corneal epithelial cells. The amnion extract contains various growth factors, and can stimulate corneal epithelial cells to grow and accelerate the repair of corneal epithelium in the process of corneal wound repair. (3) Inhibiting cornea angiogenesis. The amnion extract contains various inflammatory factors and angiogenesis inhibiting factors, and can effectively produce anti-inflammatory and angiogenesis resisting effects. (4) Inhibiting scar formation. The amnion extract contains IL-1 receptor antagonist (IL-1r) and proteolytic enzyme inhibitor, and inhibits the signal expression of transforming growth factor-beta, thereby inhibiting the differentiation of normal fibroblast into myofibroblast and reducing scar formation. (5) Anti-inflammatory and anti-infectious effects. The amnion extracting solution has a wide antibacterial spectrum and has obvious antibacterial effects on common gram-positive cocci, gram-negative cocci, fungi and even multiple drug-resistant strains of eye infection. The antibacterial activity of the compound is obviously stronger than that of chloramphenicol and sulfanilamide, and is equivalent to that of clindamycin, cefuroxime sodium and tobramycin; the sterilization efficiency is particularly high.
According to the invention, trehalose is added into a balanced salt solution, wherein the trehalose is non-reducing disaccharide formed by combining two glucose molecules through hemiacetal hydroxyl, and is widely present in bacteria, algae, yeast and lower plants, and particularly contains up to 20% of dry weight in fungi such as mould, mushroom and the like. The compound is a nonspecific biological protective agent with unique anti-dehydration, anti-freezing and anti-hypertonic protective effects, has great research on the aspects of dry eye treatment, cornea preservation and the like, and is a potential drug for effectively preventing and treating dry eye. Trehalose inhibits the induction of proinflammatory cytokines and the expression of matrix metalloproteinases in corneal and conjunctival epithelial cells, and after hyaluronate is added, the action of trehalose is enhanced to form glycosaminoglycan polysaccharides with lubricating and water-retaining properties. Trehalose reduces apoptosis and reduces ocular surface oxidation, inflammation and proteolytic activity. It also can inhibit scar formation and neovascularization.
Hyaluronic acid, also known as hyaluronic acid, is an acidic mucopolysaccharide, and is a mucopolysaccharide substance composed of disaccharide repeating units of N, acetylglucosamine and glucuronic acid. The hyaluronic acid plays roles of lubricating joints, regulating permeability of vessel walls, regulating diffusion and running of protein and water electrolytes, promoting wound healing and the like by unique molecular structure and physicochemical properties. More importantly, the hyaluronic acid has special water retention effect, is the best natural moisture retention substance discovered at present, and a 2% hyaluronic acid aqueous solution can firmly retain 98% of water. The hyaluronic acid has the function of promoting wound healing, and can promote cell migration and proliferation and promote wound healing by combining with a receptor to activate protein kinase, pulling actin filaments on cytoskeleton and other reactions. The hyaluronic acid has good effects on dry eye, repairing corneal epithelium after LASIK operation, improving tear secretion and reducing corneal fluorescein staining.
The invention has the beneficial effects that:
the surfactant cocoamidopropyl betaine is added, so that grease, tissue debris and the like in the operation can be removed, and the cleanness of the operation field is improved. The combined application of the digitonin and esculetin can improve the regulating function of ciliary muscle, relieve asthenopia and protect retina, stabilize tear film, prolong tear film rupture time, keep cornea moist, and maintain normal growth of epithelial cells. The amnion extract has good biological characteristics of fibrosis resistance, inflammation resistance, low immunological rejection and the like, can inhibit the formation of scars and new blood vessels, promotes the healing of damaged tissues of eyes, and simultaneously has various bactericidal substances, can play an effective antibacterial role and reduce the possibility of infection. The combination of trehalose with hyaluronic acid enhances the action of trehalose to form glycosaminoglycan polysaccharides with lubricating and water-retaining properties, while reducing apoptosis and reducing ocular surface oxidation, inflammation and proteolytic activity. The pH value and osmotic pressure of the washing liquid are similar to those of tears, so that the stability of the tear film on the ocular surface after operation can be maintained.
Through the combined application of the components, the grease in an operation area, tissue scraps generated in the operation and the like can be more easily cleaned, the cleanliness of the operation area is improved, the number of bacteria in a conjunctival sac is reduced, the tissue repair is promoted, the postoperative inflammatory reaction is relieved, and the discomfort such as eye edema, congestion, dryness and the like is relieved. Meanwhile, the solutions have small irritation, no toxic or side effect and low cost, and are suitable for wide clinical application.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be obtained by a person skilled in the art without making any creative effort based on the embodiments in the present invention, belong to the protection scope of the present invention.
Example 1
The embodiment provides an external eye surgical irrigating fluid which comprises the following components in percentage by mass: NaCl0.64%, KCL 0.075%, CaCl2 & 2H2O 0.048.048%, MgCl2 & 6H 2 O 0.03％、C2H3NaO2·3H2O0.39％、C 6 H 5 Na 3 O 7 ·2H 2 0.17% of O, 0.001% of cocamidopropyl betaine, 0.005% of digitonin, 0.01% of esculetin, 1% of amniotic membrane extract, 1% of trehalose, 0.5% of hyaluronic acid and the balance of purified water.
The preparation method of the amnion extracting solution comprises the following steps: collecting placenta obtained by caesarean section, cleaning, separating amnion, grinding with liquid nitrogen, adding medical normal saline at weight-volume ratio of 1: 8, and homogenizing to obtain homogenate; standing the homogenate at 0-4 ℃ for 3 days, heating at 100-120 ℃ for 45 minutes, and filtering to obtain a filtrate; adjusting the pH value of the filtrate to 3, standing, filtering, and taking the filtrate; adjusting the pH value of the filtrate to 7.2, filtering with a 0.22um filter membrane under aseptic conditions, collecting the filtrate, namely the placenta tissue extract, and preserving at 0-4 ℃ for later use.
Wherein the purified water is drinking water obtained by distillation, ion exchange or reverse osmosis.
The preparation method of the external eye surgery irrigating solution comprises the following steps:
the method comprises the following steps: taking NaCl, KCL and CaCl 2 ·2H 2 O、MgCl 2 ·6H 2 O、C 2 H 3 NaO 2 ·3H 2 O and C 6 H 5 Na 3 O 7 ·2H 2 Adding O into the purified water, then adding into a stirring device after disinfection treatment, and dissolving and stirring the mixed materials uniformly;
step three: adjusting the pH value to 7.5, and obtaining a balanced salt solution, wherein the osmotic pressure is about 300 mOsm/L;
step four: adding digitonin, esculetin, hyaluronic acid and trehalose into the balanced salt solution, adding into a sterilized stirring device, and dissolving and stirring the mixture uniformly;
step five: adding cocamidopropyl betaine, slowly stirring uniformly, adjusting the pH value to 7.2, and adjusting the osmotic pressure: 300mOsm/L, heating at 100-120 ℃ for 45 minutes, cooling to room temperature, placing in a 4-degree refrigerator, and standing for 30 min;
step six: adding amnion extract, filtering with 0.22um filter membrane under aseptic condition, and sealing and storing filtrate at 0-4 deg.C.
Example 2
The embodiment provides an external eye surgical irrigating fluid which comprises the following components in percentage by mass: NaCl0.64%, KCL 0.075%, CaCl2 & 2H2O 0.048.048%, MgCl2 & 6H 2 O 0.03％、C2H3NaO2·3H2O0.39％、C 6 H 5 Na 3 O 7 ·2H 2 0.17% of O, 0.0005% of cocamidopropyl betaine, 0.006% of digitonin, 0.005% of esculetin, 1% of amnion extract, 0.01% of trehalose, 2% of hyaluronic acid and the balance of purified water.
The preparation method of the amnion extracting solution comprises the following steps: collecting placenta obtained by caesarean section, cleaning, separating amnion, grinding with liquid nitrogen, adding medical normal saline at weight-volume ratio of 1: 5, and homogenizing to obtain homogenate; standing the homogenate at 0-4 ℃ for 7 days, heating at 100-120 ℃ for 30 minutes, and filtering to obtain a filtrate; adjusting the pH value of the filtrate to 3, standing, filtering, and taking the filtrate; adjusting the pH value of the filtrate to 7.2, filtering with a 0.20um filter membrane under aseptic conditions, collecting the filtrate, namely the placenta tissue extract, and preserving at 0-4 ℃ for later use.
Wherein the purified water is drinking water obtained by distillation, ion exchange or reverse osmosis.
The preparation method of the external eye surgery irrigating solution comprises the following steps:
the method comprises the following steps: taking NaCl, KCL and CaCl 2 ·2H 2 O、MgCl 2 ·6H 2 O、C 2 H 3 NaO 2 ·3H 2 O and C 6 H 5 Na 3 O 7 ·2H 2 Adding O into the purified water, then adding into a stirring device after disinfection treatment, and dissolving and stirring the mixed materials uniformly;
step three: adjusting the pH value to 7.4, and the osmotic pressure to about 300mOsm/L to obtain a balanced salt solution;
step four: adding digitonin, esculetin, hyaluronic acid and trehalose into the balanced salt solution, adding into a sterilized stirring device, and dissolving and stirring the mixture uniformly;
step five: adding cocamidopropyl betaine, slowly stirring uniformly, adjusting pH value to 7.2, and adjusting osmotic pressure: 300mOsm/L, heating at 100-120 ℃ for 60 minutes, cooling to room temperature, placing in a 4-degree refrigerator, and standing for 30 min;
step six: adding amnion extract, filtering with 0.20um filter membrane under aseptic condition, and sealing and storing filtrate at 0-4 deg.C.
Example 3
The embodiment provides an external eye surgical irrigating fluid which comprises the following components in percentage by mass: NaCl0.64%, KCL 0.075%, CaCl2 & 2H2O 0.048.048%, MgCl2 & 6H 2 O 0.03％、C2H3NaO2·3H2O0.39％、C 6 H 5 Na 3 O 7 ·2H 2 0.17% of O, 0.005% of cocamidopropyl betaine, 0.001% of digitonin, 0.03% of esculetin, 0.01% of amnion extracting solution, 1% of trehalose, 0.01% of hyaluronic acid and the balance of purified water.
The preparation method of the amnion extracting solution comprises the following steps: collecting placenta obtained by caesarean section, cleaning, separating amnion, grinding with liquid nitrogen, adding medical normal saline at weight-volume ratio of 1: 10, and homogenizing to obtain homogenate; standing the homogenate at 0-4 ℃ for 1 day, heating at 100-120 ℃ for 60 minutes, and filtering to obtain a filtrate; adjusting the pH value of the filtrate to 3, standing, filtering, and taking the filtrate; adjusting the pH value of the filtrate to 7.2, filtering with a 0.22um filter membrane under aseptic conditions, collecting the filtrate, namely the placenta tissue extract, and preserving at 0-4 ℃ for later use.
Wherein the purified water is drinking water obtained by distillation, ion exchange or reverse osmosis.
The preparation method of the external eye surgery irrigating solution comprises the following steps:
the method comprises the following steps: taking NaCl, KCL and CaCl 2 ·2H 2 O、MgCl 2 ·6H 2 O、C 2 H 3 NaO 2 ·3H 2 O and C 6 H 5 Na 3 O 7 ·2H 2 Adding O into the purified water, then adding into a stirring device after disinfection treatment, and dissolving and stirring the mixed materials uniformly;
step three: adjusting the pH value to 7.6, and obtaining a balanced salt solution, wherein the osmotic pressure is about 300 mOsm/L;
step four: adding digitonin, esculetin, hyaluronic acid and trehalose into the balanced salt solution, adding into a sterilized stirring device, and dissolving and stirring the mixture uniformly;
step five: adding cocamidopropyl betaine, slowly stirring uniformly, adjusting the pH value to 7.2, and adjusting the osmotic pressure: 300mOsm/L, heating at 100-120 ℃ for 30 minutes, cooling to room temperature, placing in a 4-degree refrigerator, and standing for 30 min;
step six: adding amnion extract, filtering with 0.22um filter membrane under aseptic condition, and sealing and storing filtrate at 0-4 deg.C.
Example 4
The embodiment provides an external eye surgical irrigating solution which comprises the following components in percentage by mass: NaCl0.64%, KCL 0.075%, CaCl2 & 2H2O 0.048.048%, MgCl2 & 6H 2 O 0.03％、C2H3NaO2·3H2O0.39％、C 6 H 5 Na 3 O 7 ·2H 2 0.17% of O, 0.008% of cocamidopropyl betaine, 0.006% of digitonin, 0.01% of esculetin, 1% of amniotic membrane extract, 0.5% of trehalose, 2% of hyaluronic acid and the balance of water.
The preparation method of the amnion extracting solution comprises the following steps: collecting placenta obtained by caesarean section, cleaning, separating amnion, grinding with liquid nitrogen, adding medical normal saline at weight-volume ratio of 1: 6, and homogenizing to obtain homogenate; standing the homogenate at 0-4 ℃ for 2 days, heating at 100-120 ℃ for 50 minutes, and filtering to obtain a filtrate; adjusting the pH value of the filtrate to 3, standing, filtering, and taking the filtrate; adjusting the pH value of the filtrate to 7.2, filtering with a 0.22um filter membrane under aseptic conditions, collecting the filtrate, namely the placenta tissue extract, and preserving at 0-4 ℃ for later use.
Wherein the purified water is drinking water obtained by distillation, ion exchange or reverse osmosis.
The preparation method of the external eye surgery irrigating solution comprises the following steps:
the method comprises the following steps: taking NaCl, KCL and CaCl 2 ·2H 2 O、MgCl 2 ·6H 2 O、C 2 H 3 NaO 2 ·3H 2 O and C 6 H 5 Na 3 O 7 ·2H 2 Adding O into the purified water, then adding into a stirring device after disinfection treatment, and dissolving and stirring the mixed materials uniformly;
step three: adjusting the pH value to 7.5, and obtaining a balanced salt solution, wherein the osmotic pressure is about 300 mOsm/L;
step four: adding digitonin, esculetin, hyaluronic acid and trehalose into the balanced salt solution, adding into a sterilized stirring device, and dissolving and stirring the mixture uniformly;
step five: adding cocamidopropyl betaine, slowly stirring uniformly, adjusting the pH value to 7.2, and adjusting the osmotic pressure: 300mOsm/L, heating at 100-120 ℃ for 45 minutes, cooling to room temperature, placing in a 0-4 ℃ refrigerator, and standing for 30 min;
step six: adding the amnion extracting solution, filtering with a 0.22um filter membrane under an aseptic condition, and taking the filtrate for sealing and storing at 0-4 ℃ to obtain the amnion biological membrane.
Example 5
The embodiment provides an external eye surgical irrigating fluid which comprises the following components in percentage by mass: NaCl0.64%, KCL 0.075%, CaCl 2 ·2H 2 O 0.048％、MgCl 2 ·6H 2 O 0.03％、C 2 H 3 NaO 2 ·3H 2 O0.39％、C 6 H 5 Na 3 O 7 ·2H 2 0.17% of O, 0.01% of cocamidopropyl betaine, 0.004% of digitonin, 0.03% of esculetin, 0.5% of amniotic membrane extract, 1% of trehalose, 1% of hyaluronic acid and the balance of water.
The preparation method of the amnion extracting solution comprises the following steps: collecting placenta obtained by caesarean section, cleaning, separating amnion, grinding with liquid nitrogen, adding medical normal saline at weight-volume ratio of 1: 9, and homogenizing to obtain homogenate; standing the homogenate at 0-4 ℃ for 5 days, heating at 100-120 ℃ for 40 minutes, and filtering to obtain a filtrate; adjusting the pH value of the filtrate to 3, standing, filtering, and taking the filtrate; adjusting the pH value of the filtrate to 7.2, filtering with a 0.22um filter membrane under aseptic conditions, taking the filtrate, namely the placenta tissue extracting solution, and preserving at 0-4 ℃ for later use.
Wherein the purified water is drinking water obtained by distillation, ion exchange or reverse osmosis.
The preparation method of the external eye surgery irrigating solution comprises the following steps:
the method comprises the following steps: taking NaCl, KCL and CaCl 2 ·2H 2 O、MgCl 2 ·6H 2 O、C 2 H 3 NaO 2 ·3H 2 O and C 6 H 5 Na 3 O 7 ·2H 2 O, adding the mixture into the purified water, and then adding the purified water into a stirring device after disinfection treatment to dissolve and stir the mixed materials uniformly;
step three: adjusting pH to 7.4-7.6, and osmotic pressure to 300mOsm/L to obtain balanced salt solution;
step four: adding digitonin, esculetin, hyaluronic acid and trehalose into the balanced salt solution, adding into a sterilized stirring device, and dissolving and stirring the mixture uniformly;
step five: adding cocamidopropyl betaine, slowly stirring uniformly, adjusting pH value to 7.2, and adjusting osmotic pressure: 300mOsm/L, heating at 100-120 ℃ for 50 minutes, cooling to room temperature, placing in a 0-4 ℃ refrigerator, and standing for 30 min;
step six: adding amnion extract, filtering with 0.22um filter membrane under aseptic condition, and sealing and storing filtrate at 0-4 deg.C.
Animal experiments
Subjects: 1 month old guinea pig 30
The experimental method comprises the following steps: the 30 guinea pigs were divided into 6 groups of 60 eyes, each group consisting of 5 eyes and 10 eyes, each group consisting of group A (example 1), group B (example 2), group C (example 3), group D (example 4), group E (example 5) and group F blank control group (sodium lactate gelin solution), and the same amount, temperature (at room temperature) and time for rinsing were used to rinse with different rinsing solutions. After rinsing, the degree of conjunctival congestion and corneal edema were observed for 30min and 60 min.
The experimental results are as follows: A. no conjunctival congestion and corneal edema were observed in B, C group and F group, while mild conjunctival congestion and no corneal edema were observed in D, E group.
Clinical case implementation
The general data is selected from 5 months to 7 months from 2019 of the family I, infectious eye diseases (such as blepharitis, acute conjunctivitis and the like) are eliminated, 45 patients who need to undergo laser cornea refractive surgery for smooth lacrimal passage irrigation, 90 eyes, 25 men, 50 eyes, 20 women and 40 eyes, and the age is 17-40 years old. Wherein LASEK 30 eye, LASIK15 eye, Femto-LASIK 30 eye, SMILE15 eye.
Test method
The 45 patients were randomized into A, B, C3 groups of 30 eyes each, wherein each group contained LASEK 10, LASIK5, Femto-LASIK 10, SMILE 5 eyes. The group A uses a sodium lactate geline solution, the group B uses 100ml of the sodium lactate geline solution, 2 ten thousand units of gentamicin and 1mg of dexamethasone sodium phosphate are added, the group C uses the washing liquid of the embodiment 1, and the 3 different liquids are used as operation washing liquids to wash conjunctival sac, corneal flap, corneal stroma bed and the like. In all cases, the eyes are spotted with chloramphenicol eye drops for 3 times per day after 72 hours of the operation, and nursing staff are washed and disinfected routinely 1 hour before the operation to prepare before the refractive operation.
1. Performing conjunctival sac bacterial culture by aseptic operation before and after operation irrigation
The specimen is collected by rotating and smearing lower fornix part and lower bulbar conjunctiva with sterile cotton swab to avoid contacting eyelash and periocular skin, and is sent to clinical laboratory, and cultured in basic culture medium at 35 deg.C for 3 days with automatic bacteria identifier (VITER2) produced by Meiriee company, France, and by special person.
2. The selected 3 kinds of washing solutions are the same operator, and the same amount, the same temperature (normal temperature) and the same washing time are used for washing. After washing, the degree of conjunctival congestion was observed for 15min and 30 min. Redness grading standard of bulbar conjunctiva, no redness: (one); mild hyperemia: congestion is limited to the palpebral fissure, and blood vessels appear bright red, (+); moderate congestion: hyperemia clearly reached the fornix, and vascular hyperemia was deep red, (+ +); severe hyperemia: diffuse redness of the whole conjunctiva, and redness of blood vessels, which is a purple red, blurred color (+++).
3. And comparing the oil content in the tears after washing. Oil content in tears is graded standard, no oil: (one); the tears are seen with a small amount of grease, thin, and flaky, and are scattered on the ocular surface, (+); medium-amount grease: the tear oil has large amount, thick texture, large tablet shape, and small amount of granular white lipid secretion, (++); a large amount of grease: the tears appear as a large amount of thick, dirty oil, and the whole ocular surface shows a large amount of gray-white lipid secretion (+++).
4. Effect on ocular tear film stability
Before and after operation, 1d and 7d respectively carry out basic tear secretion test (Schirmer I test, SIt) and tear film rupture time (BUT) examination, and compare the difference between the BUT and the SIt of each group before and after operation.
Effect of post-LASEK haze formation
Observing and recording the formation condition of each group of haze by using slit lamps at 1w and 4w respectively after operation, wherein the grade 0 is 0, and the cornea is completely transparent; grade 1, score 1, and low-density turbidity can be seen only by careful observation by a slit lamp direct focusing illumination method; grade 2, 2 points, mild turbidity is easily seen by a slit lamp illumination method, and the vision is affected; grade 3, medium density turbidity, and shielding part of iris structure; grade 4 marks 4 points, severe cloudiness, obscuration of intraocular structures.
Results of the experiment
1.3 groups of patients the results of bacterial culture before and after rinsing are shown in Table 1.
Table 13 groups of patients had positive rate of bacteria and positive distribution of bacteria pellets before and after washing
Injecting: the coagulating bacteria is coagulase negative staphylococcus; surface bacteria: staphylococcus epidermidis
The conjunctival sac bacteria culture positive rate of 3 groups of patients before washing has no significance (P >0.05) in the difference among groups, and the conjunctival sac bacteria culture positive rate after washing has no significance (P >0.05) in the difference among groups. The culture difference of the conjunctival sac bacteria before and after the washing of the 3 groups of patients has significance (P < 0.05).
The conjunctival congestion conditions of the 2.3 groups of cases 15min and 30min after rinsing are compared in tables 2 and 3.
Comparison of conjunctival congestion 15min after rinsing in Table 23 groups
The rank-sum test showed significant differences (P <0.05) between the groups in 3 cases at 15min post-flush conjunctival hyperemia, so group B was considered to be more irritating, group a was intermediate, and group C was considered to be less irritating.
Comparison of conjunctival hyperemia 30min after rinsing in Table 33 groups
The rank-sum test showed significant differences between the groups in 3 cases at 30min post-flush conjunctival hyperemia (P <0.05), so group B was considered to be more irritating, group a was intermediate, and group C was considered to be less irritating.
3. The oil content in the tears after rinsing was compared and is shown in table 4.
TABLE 43 comparison of oil and fat content in tear after rinsing
Through the rank-sum test, the content of oil in tears in 3 groups of cases after washing is significantly different among three groups (P <0.05), so the content of oil in tears in C group is considered to be the least, the most in A group and the B group is considered to be in the middle.
4. Effect on stability of ocular tear film
A. The postoperative 1d and 7dBUT of the patients in the group B are obviously shortened compared with the preoperative (P is less than 0.01), and the wet length of SIt filter paper is also obviously shortened compared with the preoperative (P is less than 0.01); both postoperative 1d BUT and SIt of group C patients were slightly shortened (P <0.01) compared to preoperative; BUT of patients in group C is still slightly shortened compared with that before operation at 7d after operation (P <0.01), and SIt is basically recovered to the level before operation (P > 0.05); no drug-induced keratoconjunctival toxicity or allergic reaction was observed in all patients during and after the operation.
5. The effect on post-LASEK haze development is shown in tables 5 and 6
TABLE 53 comparison of haze distributions of groups 1w after LASEK rinsing
The rank sum test showed that 3 cases had significant differences (P <0.05) between the three groups in the distribution of haze in each 1w group after washing, so the haze in each 1w group after washing was considered to occur, with the least in group C, the most in group a and the middle in group B.
TABLE 63 comparison of haze distributions in 4w groups after LASEK rinsing
TABLE 63 comparison of haze distribution in 4w groups after LASEK rinsing
The rank-sum test showed significant differences in the 4w haze distribution of 3 cases after washing (P <0.05) among the three groups, so the 4w haze distribution was considered to occur after washing, with the least in group C, the most in group a and the middle in group B.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and should not be taken as limiting the scope of the present invention, which is intended to cover any modifications, equivalents, improvements, etc. within the spirit and scope of the present invention.
Claims (4)
1. An external eye operation flushing fluid is characterized by comprising the following components in percentage by massThe composition comprises the following components: NaCl 0.64%, KCL 0.075%, CaCl 2 ·2H 2 O 0.048％、MgCl 2 ·6H 2 O 0.03％、C 2 H 3 NaO 2 ·3H 2 O 0.39％、C 6 H 5 Na 3 O 7 ·2H 2 0.17% of O, 0.0005% -0.01% of cocamidopropyl betaine, 0.001% -0.006% of digitonin, 0.005% -0.03% of esculetin, 0.01% -1% of an amniotic membrane extract, 0.01% -1% of trehalose, 0.01% -2% of hyaluronic acid and the balance of purified water, wherein the preparation method of the amniotic membrane extract comprises the following steps: taking a placenta born by caesarean section, cleaning, separating an amnion, grinding by liquid nitrogen, adding medical normal saline according to the weight-volume ratio of 1: 5-10, and homogenizing to obtain homogenate; standing the homogenate at 0-4 ℃ for 1-7 days, heating at 100-120 ℃ for 30-60 minutes, filtering, and taking a filtrate; adjusting the pH value of the filtrate to 3, standing, filtering, and taking the filtrate; adjusting the pH value of the filtrate to 7.2, filtering with a 0.20-0.22um filter membrane under aseptic conditions, collecting the filtrate, namely the placenta tissue extract, and storing at 0-4 ℃ for later use.
2. The irrigating solution for external eye surgery according to claim 1, which comprises the following components by mass percent: NaCl 0.64%, KCL 0.075%, CaCl 2 ·2H 2 O 0.048％、MgCl 2 ·6H 2 O 0.03％、C 2 H 3 NaO 2 ·3H 2 O 0.39％、C 6 H 5 Na 3 O 7 ·2H 2 0.17 percent of O, 0.001 to 0.005 percent of cocamidopropyl betaine, 0.004 to 0.006 percent of digitonin, 0.01 to 0.3 percent of esculetin, 0.5 to 1 percent of amnion extract, 0.5 to 1 percent of trehalose, 0.5 to 1 percent of hyaluronic acid and the balance of water.
3. An extra-ocular irrigating solution according to claim 1, wherein: the purified water is drinking water obtained by a distillation method, an ion exchange method or a reverse osmosis method.
4. A method for preparing an irrigating solution for external eye surgery according to any of claims 1 to 3, which comprises the steps of:
the method comprises the following steps: taking NaCl, KCL and CaCl 2 ·2H 2 O、MgCl 2 ·6H 2 O、C 2 H 3 NaO 2 ·3H 2 O and C 6 H 5 Na 3 O 7 ·2H 2 Adding O into the purified water, then adding into a stirring device after disinfection treatment, and dissolving and stirring the mixed materials uniformly;
step three: adjusting pH to 7.4-7.6, and osmotic pressure to 300mOsm/L to obtain balanced salt solution;
step four: adding digitonin, esculetin, hyaluronic acid and trehalose into the balanced salt solution, adding into a sterilized stirring device, and dissolving and stirring the mixture uniformly;
step five: adding cocamidopropyl betaine, slowly stirring uniformly, adjusting the pH value to 7.2, and adjusting the osmotic pressure: 300mOsm/L, heating at 100-120 ℃ for 30-60 minutes, cooling to room temperature, placing in a 4-degree refrigerator, and standing for 30 min;
step six: adding amnion extract, filtering with 0.20-0.22um filter membrane under aseptic condition, and sealing and storing the filtrate at 0-4 deg.C.
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| DE19853007A1 (en) * | 1998-11-17 | 2000-05-31 | Matthias Meyer | Irrigation solution for eye surgery, especially cataract surgery, containing hyaluronic acid to protect corneal endothelium |
| CN1712020A (en) * | 2004-06-23 | 2005-12-28 | 中山大学中山眼科中心 | Production of amniotic extractive liquid and use thereof |
| CN101658491A (en) * | 2009-09-24 | 2010-03-03 | 哈尔滨医科大学 | Amnion eye drops for curing cornea alkali burn |
| CN106420809A (en) * | 2016-08-31 | 2017-02-22 | 浙江济民制药股份有限公司 | Perfusate for ophthalmologic operations |
| WO2019030767A1 (en) * | 2017-08-10 | 2019-02-14 | Tathagata Dutta | Ophthalmic solution of antioxidant |
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|---|---|---|---|---|
| DE19853007A1 (en) * | 1998-11-17 | 2000-05-31 | Matthias Meyer | Irrigation solution for eye surgery, especially cataract surgery, containing hyaluronic acid to protect corneal endothelium |
| CN1712020A (en) * | 2004-06-23 | 2005-12-28 | 中山大学中山眼科中心 | Production of amniotic extractive liquid and use thereof |
| CN101658491A (en) * | 2009-09-24 | 2010-03-03 | 哈尔滨医科大学 | Amnion eye drops for curing cornea alkali burn |
| CN106420809A (en) * | 2016-08-31 | 2017-02-22 | 浙江济民制药股份有限公司 | Perfusate for ophthalmologic operations |
| WO2019030767A1 (en) * | 2017-08-10 | 2019-02-14 | Tathagata Dutta | Ophthalmic solution of antioxidant |
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