CN111228034A - Drug-loading controlled-release lacrimal duct embolus and preparation method thereof - Google Patents
Drug-loading controlled-release lacrimal duct embolus and preparation method thereof Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F9/00—Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
- A61F9/0008—Introducing ophthalmic products into the ocular cavity or retaining products therein
- A61F9/0017—Introducing ophthalmic products into the ocular cavity or retaining products therein implantable in, or in contact with, the eye, e.g. ocular inserts
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/042—Polysaccharides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/048—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/41—Anti-inflammatory agents, e.g. NSAIDs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
Abstract
The invention discloses a medicine-carrying controlled-release lacrimal duct embolus which comprises a main body tube, a fixing cap and an outer tube, wherein the main body tube is of a tubular structure with openings at two ends; the fixing cap is of a hemispherical structure, a plurality of tear guide holes are uniformly formed in the fixing cap, a clamping plate II is arranged at the lower end of the fixing cap, and the fixing cap is in threaded connection with the top end of the main pipe through the clamping plate II; the outer pipe is sleeved outside the main pipe, the upper end and the lower end of the outer pipe are movably clamped with the clamping plate II and the clamping plate I respectively, the outer pipe is provided with a strip-shaped through groove, the strip-shaped through groove penetrates through the outer pipe, and a mixture of the antibacterial and anti-inflammatory drug and the controlled-release drug carrier is dripped into the strip-shaped through groove and the strip-shaped drug carrying groove; the invention has reasonable structural design, is safe and reliable, is beneficial to relieving xerophthalmia, keratoconjunctivitis and acute dacryocystitis, and is suitable for large-scale popularization.
Description
Technical Field
The invention relates to the technical field of ophthalmic instruments, in particular to a drug-loading controlled-release lacrimal duct embolus and a preparation method thereof.
Background
Dry eye is a common and frequently encountered disease in ophthalmology, and refers to a variety of diseases characterized by ocular surface tissue disorders due to the decrease in tear film stability caused by abnormalities in the quality and quantity of tears or kinetics caused by any cause, accompanying ocular discomfort, and the incidence of dry eye is on the rise due to the influence of various factors such as environmental conditions and working pressure.
At present, no effective treatment method and medicine are available for treating the dry eye, and the substitution treatment is the main method at present, namely, the artificial tear substitution treatment and the hormone eye drops anti-inflammatory treatment are adopted, but the substitution treatment needs long-term or even lifelong medication, the additive in the artificial tear can aggravate the dry eye, and the hormone is used to induce the risk of a plurality of serious complications, including the possibility of glaucoma, cataract, infection aggravation induction and the like, so the toxic and side effects are very obvious; in addition, the lacrimal duct embolus is adopted to block the lacrimal canaliculus, and the method is simple and effective; the main principle is that the plug blocks the lacrimal canaliculus to prevent the discharge of the lacrimal fluid, prolong the staying time of the lacrimal fluid on the ocular surface, moisten and nourish the ocular surface tissue, and recover and maintain the normal structure of the ocular surface tissue. However, in the use process of the existing lacrimal duct embolus, as the lacrimal duct guiding hole is not arranged, the lacrimal fluid is completely blocked in the lacrimal canaliculus, and the inflammation of the lacrimal canaliculus and the lacrimal sac is easily caused.
At present, the administration route aiming at the keratoconjunctivitis is still mainly the eye conjunctival sac administration, the dosage forms are generally eye drops and eye ointment, and the dosage forms have the problems of low bioavailability of an absorbent of the medicine, medicine flowing out from a lacrimal canaliculus through a nasolacrimal duct, medicine overflow and the like, so that the repeated administration is needed; meanwhile, the eye ointment formulation is easy to cause fog due to factors such as substrate transparency, refractive index and the like, and the compliance of pathogenic people is reduced. The drug-carrying controlled release lacrimal passage embolus can be continuously administered, and the action time of the drug is prolonged.
Disclosure of Invention
Aiming at the technical problems, the invention provides a degradable drug-loading controlled-release lacrimal passage embolus and a preparation method thereof.
The technical scheme of the invention is as follows: a drug-loading controlled-release lacrimal passage embolus comprises a main body tube, a fixing cap and an outer tube, wherein the main body tube is of a tubular structure with openings at two ends, a first clamping plate is fixedly sleeved at the lower end of the main body tube, and a strip-shaped drug-loading groove is formed in the main body tube; the fixing cap is of a hemispherical structure, a plurality of tear guide holes are uniformly formed in the fixing cap, a clamping plate II is arranged at the lower end of the fixing cap, and the fixing cap is in threaded connection with the top end of the main pipe through the clamping plate II; the outer tube housing is established in the main part intraductal portion, the upper and lower both ends of outer tube respectively with cardboard two and cardboard one activity joint, be provided with the bar on the outer tube and lead to the groove, the bar leads to the groove and runs through the outer tube, the bar leads to the inslot portion and the bar medicine carrying groove and all can be according to the mixture of different demands dropwise add antibiotic anti-inflammatory medicine and controlled release type drug carrier.
Furthermore, the strip-shaped drug carrying grooves are provided with 5-8 strips, the 5-8 strip-shaped drug carrying grooves are uniformly arranged along the circumferential direction of the main body pipe, the number of the strip-shaped through grooves is consistent with that of the strip-shaped drug carrying grooves, and the 5-8 strip-shaped drug carrying grooves are arranged, so that the drug carrying capacity of the lacrimal passage embolus is greatly improved, and the thorough recovery of the xerophthalmia of the patient is facilitated.
Furthermore, a degradation coating is arranged between the outer tube and the main tube, the degradation coating is made of one or a mixture of two or more of polycyanoacrylate, polycaprolactone, polyorthoester, polyesteramide, polyether urethane, polyphosphate and amino acid polymers, and the degradation coating does not harm the lacrimal passage of a patient, and can control the release speed of the lacrimal passage embolus, prolong the release time of the lacrimal passage embolus and improve the treatment effect.
Furthermore, in the mixture of the antibacterial and anti-inflammatory drug and the controlled-release drug carrier, the content of the antibacterial and anti-inflammatory drug is 1-30% (wt), and by controlling the content of the antibacterial and anti-inflammatory drug, the effect of relieving the lacrimal canaliculus inflammation of the patient can be achieved, and the stimulation of the drug concentration to the lacrimal canaliculus of the patient can be avoided.
Furthermore, the controlled-release drug carrier is a degradable polymer, in particular to a hyaluronic acid-S-S-vitamin E succinate polymer, and the vitamin E succinate is a vitamin E family member, has the production and preservation performances of good stability, difficult moisture absorption and difficult bacterial contamination, and also has the function of inhibiting the breeding of bacteria; on the other hand, the vitamin E succinate has stronger hydrophobicity, does not influence the growth of normal cells in the lacrimal canaliculus, and can utilize the physiological environment in the lacrimal canaliculus of a patient to release the medicine in a responding way.
Further, the preparation method of the hyaluronic acid-S-S-vitamin E succinate polymer comprises the following steps: (1) dissolving vitamin E succinate in dichloromethane, stirring until the vitamin E succinate is completely dissolved, adding cystamine dihydrochloride and methanol for assisting dissolution under ice bath, stirring for 1-5h, adjusting the pH value to 7-8, and performing vacuum drying treatment to obtain a vitamin E succinate derivative; (2) dissolving hyaluronic acid in phosphate buffer salt solution, adding N-hydroxysuccinimide in ice bath, and stirring for 1-4h to obtain colorless transparent viscous liquid; (3) dissolving the vitamin E succinate derivative in dimethylformamide, dropwise adding the mixed solution of the vitamin E succinate derivative and the dimethylformamide into the colorless transparent viscous liquid, continuously stirring for 2-4h, and freeze-drying the reaction product to obtain the hyaluronic acid-S-S-vitamin E succinate polymer.
Further, the antibacterial and anti-inflammatory drug is any one of roxithromycin, levofloxacin, neomycin sulfate, dexamethasone sodium phosphate, acyclovir, prednisone acetate, amikacin, fluconazole and houttuynia cordata extract; the lacrimal canaliculus of the patient is sterilized and anti-inflammatory by the antibacterial anti-inflammatory drug, so that the recovery of the keratoconjunctivitis of the patient is promoted.
Furthermore, the effective component of the houttuynia cordata extract is houttuynine sodium bisulfite which has antibacterial effect and can inhibit the breeding of bacteria in lacrimal canaliculus of patients.
The preparation method of the drug-loading controlled-release lacrimal passage embolus comprises the following steps:
s1, adding 10-120 parts by weight of modified starch into purified water with the volume of 3-6 times of the modified starch, stirring and mixing uniformly, heating to 70-90 ℃, and then gelatinizing for 0.5-1h under the stirring action until a transparent solution is formed; then adding 5-70 parts by weight of chitosan into the solution, and uniformly stirring to adjust the viscosity of the solution to 800-1700 cp;
s2, adding the solution with the viscosity adjusted in the step S1 into 5% alginic acid solution in batches according to the proportion of 13%, and stirring until the solution is completely dissolved; then adding 30-120 parts by weight of water-based gel into the solution, uniformly stirring, and treating for 0.2-1.5h at the constant temperature of 60-90 ℃;
s3, filtering the solution obtained in the step S2 by using 120-mesh 180-mesh filter cloth, filling the filtered solution into a heat-insulating barrel at the temperature of 30-70 ℃, and then carrying out vacuum degassing treatment for 0.3-1.2h until no bubbles exist;
s4, pouring the solution processed in the step S3 into a mold, standing for 1-2h, demolding, eluting with normal saline, freeze-drying, and finally sterilizing by ultraviolet light.
The application method of the drug-loading controlled-release lacrimal passage embolus comprises the following steps: when the anti-inflammatory drug and controlled release drug carrier combined device is used, a mixture of the anti-inflammatory drug and the controlled release drug carrier is dripped into a strip-shaped drug carrying groove in a main tube, then a degradation coating film covers the outer side of the main tube, an outer tube is movably sleeved on the outer side of the main tube in a penetrating manner, the mixture of the anti-inflammatory drug and the controlled release drug carrier is dripped into a strip-shaped through groove in the outer tube, the main tube is in threaded connection with a clamping plate II on a fixing cap, the outer tube is clamped and fixed between the clamping plate II and the clamping plate I, and the strip-shaped through groove is opposite to the; the rotary outer tube, the main tube and the fixing cap are placed into a lacrimal canaliculus of a patient, the fixing cap is close to one side of an eyeball of the patient, antibacterial and anti-inflammatory drugs are slowly released into the lacrimal canaliculus of the patient in a controlled release type drug carrier, the lacrimal canaliculus of the patient is treated, after the antibacterial and anti-inflammatory drugs in the strip-shaped through groove are released, the degradation film starts to degrade under the action of tears, so that the antibacterial and anti-inflammatory drugs in the strip-shaped drug-carrying groove start to be released into a conjunctival sac and the lacrimal canaliculus of the patient, finally, the outer tube, the main tube and the fixing cap start to gradually degrade in the lacrimal canaliculus of the patient, and finally, carbon.
Compared with the prior art, the invention has the beneficial effects that: the novel lacrimal passage guide cap is reasonable in structural design, and in the using process, redundant tears generated by lacrimal glands of a patient can pass through the tear guide hole in the fixing cap and are finally discharged through a nasolacrimal duct of the patient, so that the aggravation of lacrimal canaliculus inflammation of the patient due to the fact that the tears are accumulated in the lacrimal duct of the patient for a long time is avoided; the drug-loading grooves are formed in the outer tube and the main tube, and the degradation coating film is arranged between the outer tube and the main tube, so that the release period of the drug is greatly prolonged, and the therapeutic effect is achieved; the controlled-release drug carrier prepared from the hyaluronic acid-S-S-vitamin E succinate polymer has the production and storage performances of good stability, difficult moisture absorption and difficult bacterial contamination, also has the function of inhibiting the breeding of bacteria, does not influence the growth of normal cells in lacrimal canaliculus, and achieves the purpose of drug loading and controlled release by utilizing the physiological environment in the lacrimal canaliculus of a patient; the antibacterial anti-inflammatory medicine can play a remarkable role in relieving and treating acute dacryocystitis and keratoconjunctivitis, and is beneficial to treatment of acute dacryocystitis and keratoconjunctivitis of patients.
Drawings
FIG. 1 is a schematic structural diagram of a drug-loaded controlled release lacrimal passage embolus of the present invention;
FIG. 2 is a longitudinal sectional view of a drug-loaded controlled release lacrimal embolus of the present invention;
wherein, 1-main tube, 10-clamp plate I, 11-strip medicine carrying groove, 2-fixing cap, 20-tear guiding hole, 21-clamp plate II, 3-outer tube, 30-strip through groove and 4-degradable coating.
Detailed Description
Example 1: as shown in fig. 1 and 2, the drug-loading controlled-release lacrimal passage embolus comprises a main body tube 1, a fixing cap 2 and an outer tube 3, wherein the main body tube 1 is a tubular structure with openings at two ends, a clamping plate I10 is fixedly sleeved at the lower end of the main body tube 1, and a strip-shaped drug-loading groove 11 is arranged on the main body tube 1; the fixing cap 2 is of a hemispherical structure, a plurality of tear guide holes 20 are uniformly formed in the fixing cap 2, a clamping plate II 21 is arranged at the lower end of the fixing cap 2, and the fixing cap 2 is in threaded connection with the top end of the main body pipe 1 through the clamping plate II 21; the outer tube 3 is sleeved outside the main tube 1, the degradation coating 4 is arranged between the outer tube 3 and the main tube 1, the degradation coating 4 is made of polycyanoacrylate, the upper end and the lower end of the outer tube 3 are movably clamped with the clamping plate II 21 and the clamping plate I10 respectively, the outer tube 3 is provided with the strip-shaped through grooves 30, the strip-shaped through grooves 30 penetrate through the outer tube 3, the strip-shaped through grooves 30 and the strip-shaped medicine carrying grooves 11 are both dropwise filled with a mixture of antibacterial and anti-inflammatory medicines and controlled-release medicine carriers, the strip-shaped medicine carrying grooves 11 are provided with 6 strips, the 6 strip-shaped medicine carrying grooves 11 are uniformly arranged along the circumferential direction of the main tube 1, the number of the strip-shaped through grooves 30 is consistent with the number of the strip-shaped medicine carrying grooves 11, the medicine carrying amount of the lacrimal duct embolus is greatly improved by arranging the 6 strip-shaped medicine carrying grooves 11, the symptom of the patient can be relieved, the, by controlling the content of the antibacterial and anti-inflammatory drugs, the effect of relieving the lacrimal canaliculus inflammation of a patient can be achieved, and the stimulation of overhigh drug concentration to the lacrimal canaliculus of the patient can be avoided; the controlled release type drug carrier is degradable polymer aliphatic polyester, the antibacterial and anti-inflammatory drug is houttuynia cordata extract, and the controlled release type drug carrier is used for sterilizing and diminishing inflammation of lacrimal canaliculi of a patient and is beneficial to treatment of xerophthalmia of the patient.
The preparation method of the drug-loading controlled-release lacrimal passage embolus comprises the following steps:
s1, adding 60 parts by weight of modified starch into 4 times of volume of purified water, stirring and mixing uniformly, heating to 70 ℃, and then gelatinizing for 0.5h under the stirring action until a transparent solution is formed; then adding 42 parts by weight of chitosan into the solution, and uniformly stirring to adjust the viscosity of the solution to 800 cp;
s2, adding the solution with the viscosity adjusted in the step S1 into 5% alginic acid solution in batches according to the proportion of 13%, and stirring until the solution is completely dissolved; then adding 70 parts by weight of water-based gel into the solution, uniformly stirring, and treating for 0.8h at the constant temperature of 60 ℃;
s3, filtering the solution obtained in the step S2 by using 120-mesh filter cloth, filling the filtered solution into a heat-preserving barrel at 50 ℃, and then carrying out vacuum degassing treatment for 0.3h until no bubbles exist;
s4, pouring the solution processed in the step S3 into a mold, standing for 1h, demolding, eluting with normal saline, freeze-drying, and finally sterilizing by ultraviolet light.
Example 2: as shown in fig. 1 and 2, the drug-loading controlled-release lacrimal passage embolus comprises a main body tube 1, a fixing cap 2 and an outer tube 3, wherein the main body tube 1 is a tubular structure with openings at two ends, a clamping plate I10 is fixedly sleeved at the lower end of the main body tube 1, and a strip-shaped drug-loading groove 11 is arranged on the main body tube 1; the fixing cap 2 is of a hemispherical structure, a plurality of tear guide holes 20 are uniformly formed in the fixing cap 2, a clamping plate II 21 is arranged at the lower end of the fixing cap 2, and the fixing cap 2 is in threaded connection with the top end of the main body pipe 1 through the clamping plate II 21; the outer tube 3 is sleeved outside the main tube 1, the degradation coating film 4 is arranged between the outer tube 3 and the main tube 1, the degradation coating film 4 is made of polycyanoacrylate, the upper end and the lower end of the outer tube 3 are movably clamped with the clamping plate II 21 and the clamping plate I10 respectively, the outer tube 3 is provided with the strip-shaped through grooves 30, the strip-shaped through grooves 30 penetrate through the outer tube 3, the strip-shaped through grooves 30 and the strip-shaped medicine carrying grooves 11 are both dropwise filled with a mixture of antibacterial and anti-inflammatory medicines and controlled-release type medicine carriers, the strip-shaped medicine carrying grooves 11 are provided with 6 strips, the 6 strip-shaped medicine carrying grooves 11 are uniformly arranged along the circumferential direction of the main tube 1, the quantity of the strip-shaped through grooves 30 is consistent with the quantity of the strip-shaped medicine carrying grooves 11, the medicine carrying quantity of the lacrimal duct embolus is greatly improved through the arrangement of the 6 strip-shaped medicine carrying grooves 11, the content of the antibacterial and anti-inflammatory medicines, not only can play a role in relieving the lacrimal canaliculitis of a patient, but also can avoid the stimulation of overhigh concentration of the medicine to the lacrimal canaliculus of the patient; the controlled release drug carrier is a degradable polymer, in particular to a hyaluronic acid-S-S-vitamin E succinate polymer, the vitamin E succinate is a vitamin E family member, has the production and preservation performances of good stability, difficult moisture absorption and difficult bacteria contamination, and also has the function of inhibiting the breeding of bacteria; on the other hand, the vitamin E succinate has stronger hydrophobicity, does not influence the growth of normal cells in the lacrimal canaliculus, and can utilize the physiological environment in the lacrimal canaliculus of a patient to release the medicine in a responding way; the preparation method of the hyaluronic acid-S-S-vitamin E succinate polymer comprises the following steps: (1) dissolving vitamin E succinate in dichloromethane, stirring until the vitamin E succinate is completely dissolved, adding cystamine dihydrochloride and methanol for assisting dissolution under ice bath, stirring for 5h, adjusting the pH value to 8, and performing vacuum drying treatment to obtain a vitamin E succinate derivative; (2) dissolving hyaluronic acid in phosphate buffer salt solution, adding N-hydroxysuccinimide in ice bath, and stirring for 4h to obtain colorless transparent viscous liquid; (3) dissolving the vitamin E succinate derivative in dimethylformamide, dropwise adding the mixed solution of the vitamin E succinate derivative and the dimethylformamide into the colorless transparent viscous liquid, continuously stirring for 4h, and freeze-drying a reaction product to obtain the hyaluronic acid-S-S-vitamin E succinate polymer, wherein the antibacterial anti-inflammatory drug is levofloxacin, and the levofloxacin is used for sterilizing and diminishing inflammation of lacrimal canaliculus of a patient to promote the recovery of keratoconjunctivitis of the patient.
The preparation method of the drug-loading controlled-release lacrimal passage embolus comprises the following steps:
s1, adding 120 parts by weight of modified starch into purified water with the volume 6 times that of the modified starch, stirring and mixing uniformly, heating to 90 ℃, and then gelatinizing for 1 hour under the stirring action until a transparent solution is formed; then adding 70 parts by weight of chitosan into the solution, and uniformly stirring to adjust the viscosity of the solution to 1700 cp;
s2, adding the solution with the viscosity adjusted in the step S1 into 5% alginic acid solution in batches according to the proportion of 13%, and stirring until the solution is completely dissolved; then adding 120 parts by weight of water-based gel into the solution, uniformly stirring, and treating for 1.5 hours at the constant temperature of 90 ℃;
s3, filtering the solution obtained in the step S2 by using 180-mesh filter cloth, filling the filtered solution into a heat-preserving container at 70 ℃, and then performing vacuum degassing treatment for 1.2 hours until no bubbles exist;
s4, pouring the solution processed in the step S3 into a mold, standing for 2 hours, demolding, eluting with normal saline, freeze-drying, and finally sterilizing by ultraviolet light.
Example 3: as shown in fig. 1 and 2, the drug-loading controlled-release lacrimal passage embolus comprises a main body tube 1, a fixing cap 2 and an outer tube 3, wherein the main body tube 1 is a tubular structure with openings at two ends, a clamping plate I10 is fixedly sleeved at the lower end of the main body tube 1, and a strip-shaped drug-loading groove 11 is arranged on the main body tube 1; the fixing cap 2 is of a hemispherical structure, a plurality of tear guide holes 20 are uniformly formed in the fixing cap 2, a clamping plate II 21 is arranged at the lower end of the fixing cap 2, and the fixing cap 2 is in threaded connection with the top end of the main body pipe 1 through the clamping plate II 21; the outer tube 3 is sleeved outside the main tube 1, the upper end and the lower end of the outer tube 3 are movably clamped with the second clamping plate 21 and the first clamping plate 10 respectively, the outer tube 3 is provided with the strip-shaped through grooves 30, the strip-shaped through grooves 30 penetrate through the outer tube 3, the mixture of the antibacterial and anti-inflammatory drug and the controlled release drug carrier is dripped into the strip-shaped through grooves 30 and the strip-shaped drug carrier 11, the strip-shaped drug carrier 11 is provided with 6 drug carriers, the 6 strip-shaped drug carriers 11 are uniformly arranged along the circumferential direction of the main tube 1, the number of the strip-shaped through grooves 30 is consistent with that of the strip-shaped drug carriers 11, the drug carrying amount of the lacrimal passage embolus is greatly improved by arranging the 6 strip-shaped drug carriers 11, the thorough recovery of xerophthalmia of a patient is facilitated, the content of the antibacterial and anti-inflammatory drug in the mixture of the controlled release drug carrier is 15 percent (wt), the content of the antibacterial and, meanwhile, the stimulation of overhigh concentration of the medicine to the lacrimal canaliculus of a patient can be avoided; the controlled release drug carrier is a degradable polymer, in particular to a hyaluronic acid-S-S-vitamin E succinate polymer, the vitamin E succinate is a vitamin E family member, has the production and preservation performances of good stability, difficult moisture absorption and difficult bacteria contamination, and also has the function of inhibiting the breeding of bacteria; on the other hand, the vitamin E succinate has stronger hydrophobicity, does not influence the growth of normal cells in the lacrimal canaliculus, and can utilize the physiological environment in the lacrimal canaliculus of a patient to release the medicine in a responding way; the preparation method of the hyaluronic acid-S-S-vitamin E succinate polymer comprises the following steps: (1) dissolving vitamin E succinate in dichloromethane, stirring until the vitamin E succinate is completely dissolved, adding cystamine dihydrochloride and methanol for assisting dissolution under ice bath, stirring for 5h, adjusting the pH value to 8, and performing vacuum drying treatment to obtain a vitamin E succinate derivative; (2) dissolving hyaluronic acid in phosphate buffer salt solution, adding N-hydroxysuccinimide in ice bath, and stirring for 4h to obtain colorless transparent viscous liquid; (3) dissolving a vitamin E succinate derivative in dimethylformamide, dropwise adding a mixed solution of the vitamin E succinate derivative and the dimethylformamide into the colorless transparent viscous liquid, continuously stirring for 4 hours, and freeze-drying a reaction product to obtain a hyaluronic acid-S-S-vitamin E succinate polymer, wherein an antibacterial anti-inflammatory drug is dexamethasone sodium phosphate, and is used for sterilizing and diminishing inflammation of lacrimal canaliculus of a patient to promote the recovery of conjunctivitis of the patient;
the lacrimal passage embolus is made of nickel alloy material and is permanent lacrimal passage embolus.
Experimental example: 32 cases of bacterial keratoconjunctivitis patients are clinically collected in 2019.8-10 months in certain ophthalmic hospital in the city, and the 32 cases of keratoconjunctivitis patients are randomly divided into two groups, namely an experimental group and a control group; 16 patients in the experimental group adopt the lacrimal passage embolus and conjunctival sac combined administration mode to carry out anti-infection treatment, and 16 patients in the control group only adopt the conjunctival sac administration mode to treat, such as dripping levofloxacin; after 5 days of continuous treatment, 16 patients in the experimental group began to get better, and only 2 patients had slight red and swollen eyeballs; the average drug release time of the lacrimal duct embolus is 8 days, after 8 days, 16 patients in the test group are completely recovered, and the lacrimal duct embolus begins to degrade in the lacrimal canaliculus of the patient; the levofloxacin is dripped 4 times every day for 16 patients in the control group, after the levofloxacin is continuously used for 5 days, only 6 patients have improved disease conditions, 5 patients have obvious red and swollen eyeballs and mild ulcer, after the levofloxacin is continuously used for 8 days, only 11 patients completely recover, and the rest 5 patients still have inflammatory manifestations with different degrees.
In conclusion, the drug-loading controlled-release lacrimal passage embolus has controllable drug release and long drug release period, can be automatically degraded in a lacrimal canaliculus of a patient, and cannot harm the patient.
Claims (9)
1. A drug-loading controlled-release lacrimal passage embolus is characterized by comprising a main body tube (1), a fixing cap (2) and an outer tube (3), wherein the main body tube (1) is of a tubular structure with openings at two ends, a clamping plate I (10) is fixedly sleeved at the lower end of the main body tube (1), and a strip-shaped drug-loading groove (11) is arranged on the main body tube (1); the fixing cap (2) is of a hemispherical structure, a plurality of tear guide holes (20) are uniformly formed in the fixing cap (2), a second clamping plate (21) is arranged at the lower end of the fixing cap (2), and the fixing cap (2) is in threaded connection with the top end of the main pipe (1) through the second clamping plate (21); the outer tube (3) is sleeved outside the main tube (1), the upper end and the lower end of the outer tube (3) are movably clamped with the clamping plate II (21) and the clamping plate I (10) respectively, the outer tube (3) is provided with the strip-shaped through groove (30), the strip-shaped through groove (30) penetrates through the outer tube (3), and the strip-shaped through groove (30) and the strip-shaped drug carrying groove (11) are internally and respectively dropwise filled with a mixture of antibacterial and anti-inflammatory drugs and controlled-release drug carriers according to different requirements.
2. The drug-loaded controlled-release lacrimal passage embolus according to claim 1, wherein a degradation coating (4) is arranged between the outer tube (3) and the main tube (1), and the material of the degradation coating (4) is one or a mixture of two or more of polycyanoacrylate, polycaprolactone, polyorthoester, polyesteramide, polyether urethane, polyphosphate and amino acid polymer.
3. The drug-carrying controlled-release lacrimal passage embolus as claimed in claim 1, wherein the number of the strip-shaped drug-carrying grooves (11) is 5-8, the strip-shaped drug-carrying grooves are uniformly arranged along the circumference of the main body tube (1), and the number of the strip-shaped through grooves (30) is consistent with the number of the strip-shaped drug-carrying grooves (11).
4. The drug-loaded controlled-release lacrimal passage embolus of claim 1, wherein the antibacterial and anti-inflammatory drug is contained in an amount of 1-30% (wt) in the mixture of the antibacterial and anti-inflammatory drug and the controlled-release drug carrier.
5. The drug-loaded controlled-release lacrimal passage embolus as claimed in claim 1, wherein the controlled-release drug carrier is degradable polymer, specifically hyaluronic acid-S-S-vitamin E succinate polymer.
6. The drug-loaded controlled-release lacrimal passage suppository of claim 1, wherein the antibacterial and anti-inflammatory drug is any one of roxithromycin, levofloxacin, neomycin sulfate, dexamethasone sodium phosphate, acyclovir, prednisone acetate, amikacin, fluconazole, and houttuynia cordata extract.
7. The drug-loaded controlled-release lacrimal passage suppository of claim 1, wherein the antibacterial and anti-inflammatory drug is any two of roxithromycin, levofloxacin, neomycin sulfate, dexamethasone sodium phosphate, acyclovir, prednisone acetate, amikacin, fluconazole, and houttuynia cordata extract.
8. The drug-loaded controlled-release lacrimal passage embolus of claim 6, wherein the effective component of the houttuynia cordata extract is houttuynine sodium bisulfite.
9. The method for preparing a drug-loaded controlled-release lacrimal passage embolus of claim 1, comprising the following steps:
s1, adding 10-120 parts by weight of modified starch into purified water with the volume of 3-6 times of the modified starch, stirring and mixing uniformly, heating to 70-90 ℃, and then gelatinizing for 0.5-1h under the stirring action until a transparent solution is formed; then adding 5-70 parts by weight of chitosan into the solution, and uniformly stirring to adjust the viscosity of the solution to 800-1700 cp;
s2, adding the solution with the viscosity adjusted in the step S1 into 5% alginic acid solution in batches according to the proportion of 13%, and stirring until the solution is completely dissolved; then adding 30-120 parts by weight of water-based gel into the solution, uniformly stirring, and treating for 0.2-1.5h at the constant temperature of 60-90 ℃;
s3, filtering the solution obtained in the step S2 by using 120-mesh 180-mesh filter cloth, filling the filtered solution into a heat-insulating barrel at the temperature of 30-70 ℃, and then carrying out vacuum degassing treatment for 0.3-1.2h until no bubbles exist;
s4, pouring the solution processed in the step S3 into a mold, standing for 1-2h, demolding, eluting with normal saline, freeze-drying, and finally sterilizing by ultraviolet light.
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