CN108295318B - Thermosensitive injectable lacrimal duct suppository and preparation method thereof - Google Patents
Thermosensitive injectable lacrimal duct suppository and preparation method thereof Download PDFInfo
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- CN108295318B CN108295318B CN201810093808.7A CN201810093808A CN108295318B CN 108295318 B CN108295318 B CN 108295318B CN 201810093808 A CN201810093808 A CN 201810093808A CN 108295318 B CN108295318 B CN 108295318B
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- 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
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- 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
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- A—HUMAN NECESSITIES
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Abstract
本发明公开了一种温敏可注射型泪道栓及其制备方法，其特征在于：所述的可注射泪道栓由温敏复合水凝胶材料制成，在液态情况下被注射进人或动物眼睛的下泪小管口，依靠人或动物的体温使液态的可注射泪道栓凝固，堵塞下泪小管口，其中温敏复合水凝胶材料采用浓度为泊洛沙姆407、泊洛沙姆188和水配置而成，根据需要加入粘度增强剂和/或强度增强剂。本发明的可注射泪道栓在低温条件下具有良好的流动下，可通过注射器注射进人或动物的下泪小管口，依靠人或动物体温使复合温敏复合水凝胶迅速凝固，堵塞下泪小管口，起到缓解干眼症的作用，在应用中具有简单方便，便于操作及推广的优点。
The invention discloses a temperature-sensitive injectable lacrimal duct suppository and a preparation method thereof, characterized in that the injectable lacrimal duct suppository is made of a temperature-sensitive composite hydrogel material, and is injected into a human in a liquid state Or the orifice of the lower lacrimal canaliculus of the eyes of animals, the liquid injectable lacrimal plug is solidified by the body temperature of the human or animal, and the orifice of the lower lacrimal canaliculus is blocked, and the temperature-sensitive composite hydrogel material is made of poloxamer 407, Formulated with Sharm 188 and water, adding viscosity enhancers and/or strength enhancers as required. The injectable lacrimal duct plug of the present invention has good flow under low temperature conditions, and can be injected into the lower lacrimal canaliculus of humans or animals through a syringe. The lacrimal canalicular orifice plays a role in relieving dry eye syndrome, and has the advantages of simple and convenient application, easy operation and promotion.
Description
Technical Field
The invention relates to a temperature-sensitive injectable lacrimal passage suppository and a preparation method thereof, belonging to the field of medical research of multifunctional temperature-sensitive composite hydrogel.
Background
Dry eye refers to a condition of abnormal tear mass or quantity due to any cause, which leads to a decrease in tear film stability, accompanied by ocular discomfort, ocular surface tissue changes, and the like. The common symptoms comprise dry eyes, easy fatigue, impaired vision and the like. Studies have shown that dry eye signs are due to insufficient secretion of lacrimal gland tears, mucin and lipid layers and excessive evaporation of tears, which are common among elderly people and offices working in front of computers for a long time. To date, there is no effective treatment for dry eye symptoms. Clinically, physiological saline, artificial tears and anti-immune eye drops are mainly relied on to relieve symptoms.
The treatment of the xerophthalmia in European and American countries is mainly realized by designing a lacrimal passage plug for blocking the outlet at the lower end of a lacrimal canaliculus so that the lacrimal fluid is lost as little as possible to treat the xerophthalmia. The therapeutic mechanism of the lacrimal passage suppository is mature, but the designed lacrimal passage suppository is mostly under patent protection and a detailed preparation method is not described. Based on the study of lacrimal plugs, Beetham first proposed in 1935 to thermally disrupt the lacrimal canaliculus and block the small lacrimal punctumCan relieve dry eye, and Foulds designed non-degradable gel to block lacrimal canaliculus in 1961 to treat dry eye. In 1975, Freeman Plug, designed by Freeman, opened up a new avenue for the design and preparation of future lacrimal plugs. At present, the dry eye disease treatment in domestic hospitals mainly uses lacrimal passage suppository designed and manufactured in Europe and America, and the main brands are as follows: form FitTM、SmartPlugTM、S Soft PlugTM、nug PlugsTM、ExtendTM、
Tears NaturaleTM 
And the like.
Dry eye is mainly caused by a lack of tears of the eye and mainly manifests dry eyes, foreign body sensation, photophobia, tingling and the like. The eye is stimulated to secrete tears from the lacrimal gland, which flow out through the superior and inferior lacrimal canaliculi, manifesting as lacrimation. The lacrimal passage suppository can reduce tear loss by blocking the lacrimal canaliculus orifice under the eye part, and excessive tears overflow from the lacrimal canaliculus orifice to keep the eye part moist, thereby playing a role in treating xerophthalmia.
After decades of development, the design and preparation process of the lacrimal passage suppository in foreign countries are mature, and more international patents are applied, so that the curative effect of the lacrimal passage suppository on dry eye is clear, but the preparation technology of the lacrimal passage suppository is less described in the existing foreign literature and international patents. Meanwhile, the current international lacrimal passage suppository is mainly an implantation type solid lacrimal passage suppository, and has the defects of inconvenient implantation and taking out of the eye of a patient and difficulty in mass popularization.
Disclosure of Invention
The invention provides a temperature-sensitive injectable lacrimal passage suppository and a preparation method thereof, the lacrimal passage suppository prepared by temperature-sensitive materials can be injected into the lower lacrimal passage orifices of people or animals at low temperature by adopting an injector, and the lacrimal passage suppository is solidified by the body temperature of the people or the animals to block the lower lacrimal small orifice, thereby playing the role of relieving xerophthalmia.
In-situ gel (in-situ gel), also known as in-vivo gel, refers to a semisolid or solid preparation formed by administering a polymer material in a solution or semisolid state and then responding to external stimuli (such as changes in temperature, pH value, ion species and concentration, illuminance and the like of the administration site) at the administration site to reversibly transform the conformation of the gel in a dispersion state. Among them, the physiological compatibility of the temperature sensitive gel responding to the temperature change is the best. The temperature-sensitive instant gel preparation exists in a liquid or semisolid form before storage and administration (room temperature), and a gel solution is coagulated due to temperature rise (body temperature) after local administration to form a gel with good adhesiveness and slow release performance. The temperature-sensitive instant gel has the advantages of simple production and preparation, good physiological compatibility, easy control, good adhesion and the like, and is widely applied to novel nasal, rectal and injection drug delivery systems in recent years.
The main and auxiliary materials of the temperature-sensitive instant gel mainly comprise Poloxamer407(P407), methylcellulose and other novel auxiliary materials (such as PEG-PLA block copolymer, ethylhydroxy ethylcellulose, PEG-poly epsilon-PCL block copolymer and the like). Among them, P407 is most widely applied and deeply researched in the field of temperature-sensitive instant gels because of its good temperature-sensitive gelling property and safety and easy availability.
The invention mainly utilizes a high polymer material with high biocompatibility and unique temperature-sensitive effect to research a temperature-sensitive composite hydrogel material which is liquid within 30 ℃ and is rapidly solidified above 30 ℃ to prepare the injectable lacrimal passage suppository. The liquid composite hydrogel is solidified into a lacrimal passage suppository by depending on the body temperature of human or animals, and the lacrimal canaliculus opening is blocked, so that the effect of treating the dry eye disease is achieved. The preparation process of the researched injectable lacrimal passage suppository is optimized, and the developed lacrimal passage suppository is quickly converted into a product by selecting proper preparation conditions, is popularized to the market and serves patients. Not only can obviously relieve the symptoms of the xerophthalmia, but also can lighten the burden of patients and the society and improve the treatment effect and the compliance of the patients to products.
The specific technical scheme of the invention is as follows:
a temperature-sensitive injectable lacrimal passage plug is prepared from temperature-sensitive composite hydrogel material, and is injected into the lower lacrimal passage orifice of eyes of human or animal under liquid state, and the liquid lacrimal passage plug is solidified by the body temperature of human or animal to block the lower lacrimal passage orifice.
Further, the injection temperature is below 30 ℃.
Further, the injection temperature is 10-15 ℃.
Further, the lacrimal passage suppository has the solidification temperature of not lower than 30 ℃.
Furthermore, the lacrimal passage suppository is prepared by adding a viscosity enhancer and/or a strength enhancer into a temperature-sensitive composite hydrogel material.
Further, the temperature-sensitive composite hydrogel material is P407-P188 poloxamer, P407 poloxamer-acrylic acid polymer, carboxymethyl chitosan-sodium glycerophosphate, poly (N-isopropylacrylamide) PNIPAAm homopolymerized hydrogel or polyethylene glycol (PEG) -lactic acid (PLGA) -glycolic acid (PLA) copolymer.
Further, the viscosity enhancer is sodium carboxymethylcellulose (CMC-Na), sodium polyacrylate, chitosan, cyclodextrin, carbomer 940, pectin or polyethylene glycol.
Further, the strength enhancer is polyvinyl alcohol (PVA), low molecular polyethylene wax, chitosan, cyclodextrin, hydroxypropyl cellulose or agar.
Further, the temperature-sensitive composite hydrogel material comprises poloxamer407, poloxamer 188 and water, wherein the weight ratio of poloxamer407 to poloxamer 188 to water is 40-60: 4-10: 100.
The viscosity enhancer is sodium carboxymethylcellulose (CMC-Na), and the adding ratio of the CMC-Na to water is 0.8-1.6: 100 (mass ratio).
The strength enhancer is polyvinyl alcohol (PVA), and the addition ratio of the PVA to water is 3-8: 100 (mass ratio).
Furthermore, the lacrimal passage suppository is prepared from poloxamer407, poloxamer 188 and water, wherein the weight ratio of poloxamer407 to poloxamer 188 to water is 40-60: 4-10: 100.
Furthermore, sodium carboxymethylcellulose (CMC-Na) with mass concentration is added in the preparation of the injectable lacrimal passage suppository, and the addition ratio of the CMC-Na to water is 0.8-1.6: 100 (mass ratio).
Furthermore, polyvinyl alcohol (PVA) is added in the preparation of the injectable lacrimal passage suppository, and the adding proportion of the PVA to water is 3-8: 100 (mass ratio).
The invention has the following technical effects:
1. the invention selects temperature-sensitive material to prepare the injectable lacrimal passage suppository, has good fluidity at low temperature, can be injected into the lower lacrimal passage orifice of human or animal through an injector, leads the composite hydrogel to be rapidly solidified by the body temperature of human or animal, blocks the lower lacrimal passage orifice, plays a role in relieving xerophthalmia, can reduce the local temperature of the lower lacrimal passage orifice by injecting low-temperature eye-washing liquid and the like from the outside during removal, leads the solid lacrimal passage suppository to be changed into liquid, washes through artificial tears, washes the injectable gel cleanly, and has the advantages of simple and convenient application and convenient operation and popularization.
2. The invention selects and combines main and auxiliary materials for solidification in different proportions, realizes adjustable solidification temperature, meets the requirements of human bodies and animals in different environments, and simultaneously adds the viscosity enhancer and the strength enhancer into the material, wherein the viscosity enhancer is beneficial to the attachment of the composite hydrogel on the lacrimal passage opening and can not flow off; the strength reinforcing agent can enhance the rigidity of the composite hydrogel, so that the composite hydrogel has proper hardness and strength after being cured, and can be well and automatically attached to the lacrimal passage orifice.
3. The solidification raw material, the viscosity enhancer CMC-Na and the strength enhancer PVP all accord with the medical material standard, the biocompatibility is high, the immunogenicity is free, the degradation can not be obvious under the physiological condition, the degradation and the breakage can not occur under the soaking of the tear water, the prepared injectable lacrimal passage suppository has good stability after being implanted, can not be dissolved by the tear or can not generate chemical reaction in the tear, and the like, and has the characteristics of safety, reliability and less side effect when being applied to the eyes of animals and human beings.
4. The invention designs the solidification temperature of the injectable lacrimal passage suppository to be not lower than 30 ℃ according to the body temperature of people and common animals, ensures that the lacrimal passage suppository can be solidified at the lower lacrimal passage orifice in the common living environment, simultaneously expands the temperature range of liquid injection, and easily washes out the injectable gel through low-temperature artificial tears when removing the injectable gel, thereby having wide practicability.
Drawings
FIG. 1 is a schematic view of a method of implanting a temperature-sensitive injectable lacrimal suppository of the present invention in a human eye;
FIG. 2 is a graph showing experimental results of thermosetting properties of an injectable lacrimal suppository in accordance with an embodiment of the present invention;
FIG. 3 is an electron microscope image of a temperature sensitive injectable lacrimal suppository after curing in one embodiment of the present disclosure;
the reference signs are: 1-superior lacrimal canaliculus; 2-lacrimal sac; 3-inferior lacrimal canaliculus; 4-nasolacrimal duct; 5-inferior nasal meatus; 6-lacrimal gland; 7-lacrimal duct.
Detailed Description
The project provides a temperature-sensitive intelligent injectable lacrimal passage suppository prepared from a temperature-sensitive composite hydrogel material and auxiliary materials, wherein the composite hydrogel material comprises organic silicon, acrylic polymers, polyurethane, hydrocarbon polymers and other polymethyl, acrylic resin, poly octadecyl methacrylate and the like.
As shown in figure 1, the temperature-sensitive injectable lacrimal passage suppository material has good flow under the condition of low temperature, can be injected into the lower lacrimal passage orifice of human or animals through an injector, and can be rapidly solidified by the body temperature of the human or animals to block the lower lacrimal passage orifice to play a role in relieving xerophthalmia.
According to the invention, by selecting a proper composite hydrogel material or by the proportion of the composite material, the solidification temperature of the temperature-sensitive composite hydrogel is above 30 ℃, the injection temperature can be set below 30 ℃, the temperature is changed into 10-15 ℃ for injection, and meanwhile, a viscosity enhancer and a strength enhancer are added into the temperature-sensitive composite hydrogel material, wherein the viscosity enhancer is beneficial to the composite hydrogel to be attached to the lacrimal passage opening and cannot be lost; the strength reinforcing agent can enhance the rigidity of the composite hydrogel, so that the composite hydrogel has proper hardness and strength after being cured, and can be well and automatically implanted into the lacrimal passage opening. The injectable lacrimal passage suppository is in a liquid state before being implanted into lacrimal passage, and has good fluidity; after being implanted, the composite temperature-sensitive composite hydrogel is quickly cured under the stimulation of the lacrimal passage temperature, so that the composite temperature-sensitive composite hydrogel is converted into a solid lacrimal passage suppository with certain elasticity and viscosity, is firmly attached to the lacrimal canaliculus opening, inhibits the overflow of tears, keeps the wettability of eyeballs, plays a role in treating xerophthalmia, is convenient and reliable to use, and has great market popularization value.
Example 1:
and (3) testing results: the product solidification temperature is 31 ℃; under the condition of liquid state at 15 ℃, the viscosity of the ingredients is about 8mPa & s by adopting a viscometer to measure; under the curing condition of 31 ℃, a columnar product with the diameter of 3mm and the height of 4mm is prepared, and the extrusion strength is measured to be 15 Pa. The result shows that the material can basically meet the functional requirements of the injectable lacrimal passage suppository, but has lower viscosity when in liquid state and lower mechanical strength after being solidified.
Example 2:
and (3) testing results: the product solidification temperature is 31 ℃; under the condition of liquid state at 15 ℃, the viscosity of the ingredients is about 70mPa & s by adopting a viscometer to measure; under the curing condition of 31 ℃, a columnar product with the diameter of 3mm and the height of 4mm is prepared, and the extrusion strength is measured to be 15 Pa. The result shows that the material can basically meet the functional requirement of the injectable lacrimal passage suppository, but the mechanical strength is low after the material is solidified.
Example 3:
and (3) testing results: the product solidification temperature is 31 ℃; under the condition of liquid state at 15 ℃, the viscosity of the ingredients is about 8.1 mPas measured by a viscometer; under the curing condition of 31 ℃, a columnar product with the diameter of 3mm and the height of 4mm is prepared, and the extrusion strength is measured to be 0.50 MPa. The result shows that the material can basically meet the functional requirement of the injectable lacrimal passage suppository, but has low viscosity when in a liquid state.
Example 4:
and (3) testing results: the product solidification temperature is 31 ℃; under the condition of liquid state at 15 ℃, the viscosity of the ingredients is about 72mPa & s measured by a viscometer; under the curing condition of 31 ℃, a columnar product with the diameter of 3mm and the height of 4mm is prepared, and the extrusion strength is measured to be 0.55 MPa. The result shows that the material can meet the functional requirements of the injectable lacrimal passage suppository in aspects of temperature, viscosity and strength.
Example 5:
and (3) testing results: the product solidification temperature is 30.4 ℃; under the condition of liquid state at 15 ℃, the viscosity of the ingredients is measured by a viscometer to be about 85 mPas; under the curing condition of 30.4 ℃, a columnar product with the diameter of 3mm and the height of 4mm is prepared, and the extrusion strength is measured to be 0.74 MPa. The result shows that the material can meet the functional requirements of the injectable lacrimal passage suppository in aspects of temperature, viscosity and strength.
Example 6:
and (3) testing results: the product solidification temperature is 31 ℃; under the condition of liquid state at 15 ℃, the viscosity of the ingredients is measured by a viscometer to be about 84 mPas; under the curing condition of 31 ℃, a columnar product with the diameter of 3mm and the height of 4mm is prepared, and the extrusion strength is measured to be 0.75 MPa. The result shows that the material can meet the functional requirements of the injectable lacrimal passage suppository in aspects of temperature, viscosity and strength.
Example 7
And (3) testing results: the product solidification temperature is 30 ℃; under the condition of liquid state at 15 ℃, the viscosity of the ingredients is about 62mPa & s by adopting a viscometer; under the curing condition of 30 ℃, a columnar product with the diameter of 3mm and the height of 4mm is prepared, and the extrusion strength is measured to be 0.48 MPa. The result shows that the material can meet the functional requirements of the injectable lacrimal passage suppository in aspects of temperature, viscosity and strength.
Example 8
And (3) testing results: the product solidification temperature is 31 ℃; under the condition of liquid state at 15 ℃, the viscosity of the ingredients is about 62mPa & s by adopting a viscometer; under the curing condition of 31 ℃, a columnar product with the diameter of 3mm and the height of 4mm is prepared, and the extrusion strength is measured to be 0.48 MPa. The result shows that the material can meet the functional requirements of the injectable lacrimal passage suppository in aspects of temperature, viscosity and strength.
Example 9
| Material | Name (R) | Description of parameters |
| Composite hydrogel | Acrylic acid and Poloxamer407(P407) | Acrylic acid: p407: 25:33:100 water |
| Viscosity enhancing agent | Polyacrylamide | Polyacrylamide: water 3.3:100 |
| Strength enhancer | Cyclodextrin | Cyclodextrin: water 5.8:100 |
And (3) testing results: the product solidification temperature is 32 ℃; under the condition of liquid state at 15 ℃, the viscosity of the ingredients is about 62mPa & s by adopting a viscometer; under the curing condition of 32 ℃, a columnar product with the diameter of 3mm and the height of 4mm is prepared, and the extrusion strength is measured to be 0.53 MPa. The result shows that the material can meet the functional requirements of the injectable lacrimal passage suppository in aspects of temperature, viscosity and strength.
Example 10
And (3) testing results: the product solidification temperature is 31 ℃; under the condition of liquid state at 15 ℃, the viscosity of the ingredients is about 75mPa & s measured by a viscometer; under the curing condition of 31 ℃, a columnar product with the diameter of 3mm and the height of 4mm is prepared, and the extrusion strength is measured to be 0.42 MPa. The result shows that the material can meet the functional requirements of the injectable lacrimal passage suppository in aspects of temperature, viscosity and strength.
Example 11
And (3) testing results: the product solidification temperature is 30 ℃; under the condition of liquid state at 15 ℃, the viscosity of the ingredients is measured by a viscometer to be about 55mPa & s; under the curing condition of 30 ℃, a columnar product with the diameter of 3mm and the height of 4mm is prepared, and the extrusion strength is measured to be 0.56 MPa. The result shows that the material can meet the functional requirements of the injectable lacrimal passage suppository in aspects of temperature, viscosity and strength.
The following tests for pharmaceutical properties were carried out on the materials and products of examples 1-4, with the following results:
firstly, thermal degradation characteristic experiment is carried out on temperature-sensitive composite hydrogel
The thermal degradation curve of the three-material composite hydrogel is given in fig. 2. In air and at about 4 ℃ min-1TG curve measured as the temperature increase rate. The three composite hydrogels exhibited similar thermal degradation characteristics. From the thermal decomposition curves of P407/P188 in example 1, P407/P188-PVA in example 3, and P407/P188-CMC-Na in example 2, it was found that the first-step thermal decomposition was about 32% of the thermal decomposition points of the three types of composite hydrogels at 105 ℃; the second step of thermal decomposition, namely the thermal decomposition of P407/P188 is dominant, and the molecular skeleton is broken at the temperature of 210 ℃ and 280 ℃, namely the polymer quality is greatly reduced by about 30-45%; and thirdly, thermally decomposing 345 ℃ and 600 ℃, wherein the thermal decomposition of the polymer tends to be smooth, and the degradation rates of the three composite hydrogels are increased in sequence. The data show that the product can meet the requirement of material stability at the temperature of the human body.
Secondly, thermal coagulation property experiment of the composite hydrogel:
the product prepared in example 4 cured rapidly at 31 c and experiments showed very stable adhesion in an inverted rubber tube, strong enough to be stably implanted in the lacrimal passage orifice, preventing tear loss. Meanwhile, when the temperature is reduced to below 30 ℃, the solid is changed into a liquid composite hydrogel state again, and good reversibility is shown, and the property is favorable for taking out the implanted injectable lacrimal passage suppository.
Third, implantation method experiment
The product prepared in example 4 is prepared by injecting the prepared liquid composite hydrogel into the inferior lacrimal duct orifice of the eye through a micro-syringe, and the composite hydrogel is slowly solidified when the temperature is gradually increased, so that the blockage of the inferior lacrimal duct orifice is realized, the tear loss is prevented, and the function of treating the xerophthalmia is achieved. When taken out, the gel is washed by artificial tears at 10-15 ℃ to reduce the local temperature of the lower lacrimal passage mouth, the solid gel becomes liquid, and the injectable gel is washed clean along with the artificial tears.
Fourth, structure and electron microscope experiment
As shown in FIG. 3, when the product prepared in example 4 is observed under an electron microscope, the cured composite hydrogel has a plurality of crossed pores which are stacked together layer by layer, which indicates that the hydrogel has certain elasticity and is suitable for being used as a lacrimal duct plug at the lacrimal canaliculus.
The injectable lacrimal passage suppository disclosed by the invention meets the medical material standard in material selection, has the characteristics of high biocompatibility, safety, reliability and less side effect when being applied to the eyes of animals and human beings, and has great market popularization value.
Claims (8)
1. A temperature-sensitive injectable lacrimal passage suppository is characterized in that: the lacrimal passage suppository is made of temperature-sensitive composite hydrogel materials, is injected into the lower lacrimal duct orifice of eyes of people or animals under the liquid state, the liquid composite hydrogel is solidified into the lacrimal passage suppository by depending on the body temperature of the people or the animals, the lower lacrimal duct orifice is blocked, and the solid lacrimal passage suppository is changed into the liquid state to be removed by reducing the local temperature of the lower lacrimal duct orifice;
the lacrimal passage suppository is prepared by adding a viscosity enhancer and a strength enhancer into a temperature-sensitive composite hydrogel material;
the temperature-sensitive composite hydrogel material is P407-P188 poloxamer, P407 poloxamer-acrylic acid polymer, poly (N-isopropylacrylamide) PNIPAAm homopolymerized hydrogel or polyethylene glycol (PEG) -lactic acid (PLGA) -glycolic acid (PLA) copolymer;
the viscosity enhancer is sodium carboxymethylcellulose (CMC-Na), sodium polyacrylate, chitosan, cyclodextrin, carbomer 940, pectin or polyethylene glycol;
the strength reinforcing agent is polyvinyl alcohol (PVA), low molecular polyethylene wax, chitosan, cyclodextrin, hydroxypropyl cellulose or agar.
2. The temperature-sensitive injectable lacrimal suppository of claim 1, wherein: the injection temperature is below 30 ℃.
3. The temperature-sensitive injectable lacrimal suppository of claim 2, wherein: the injection temperature is 10-15 ℃.
4. The temperature-sensitive injectable lacrimal suppository of claim 1, wherein: the lacrimal passage suppository has a solidification temperature of not lower than 30 ℃.
5. The temperature-sensitive injectable lacrimal suppository of claim 1, wherein: the viscosity enhancer is sodium carboxymethylcellulose (CMC-Na), and the addition mass ratio of CMC-Na to water = 0.8-1.6: 100.
6. The temperature-sensitive injectable lacrimal suppository of claim 1, wherein: the strength reinforcing agent is polyvinyl alcohol (PVA), and the addition mass ratio of the PVA to water is = 3-8: 100.
7. The temperature-sensitive injectable lacrimal suppository of claim 1, wherein: the temperature-sensitive composite hydrogel material comprises poloxamer407, poloxamer 188 and water, and the mass ratio of the poloxamer407 to the poloxamer 188 to the water = 40-60: 4-10: 100.
8. A preparation method of a temperature-sensitive injectable lacrimal passage suppository is characterized by comprising the following steps: the lacrimal passage suppository is prepared from poloxamer407, poloxamer 188 and water in a concentration ratio of poloxamer407 to poloxamer 188 to water = 40-60: 4-10: 100;
sodium carboxymethylcellulose (CMC-Na) is also added in the preparation of the lacrimal duct suppository, and the mass ratio of the CMC-Na to the water = 0.8-1.6: 100;
polyvinyl alcohol (PVA) is further added in the preparation of the lacrimal passage suppository, and the mass ratio of the PVA to the water = 3-8: 100.
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| JP7739316B2 (en) * | 2020-03-12 | 2025-09-16 | レッドウッド ファーマ アクティエボラーグ | New uses and methods of treatment |
| CN111467302A (en) * | 2020-04-13 | 2020-07-31 | 徐州医科大学 | Injectable temperature-sensitive refrigeration hydrogel capable of inducing local sub-low temperature to treat craniocerebral trauma |
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Denomination of invention: A thermosensitive injectable lacrimal duct suppository and its preparation method Granted publication date: 20210706 Pledgee: Xi'an Caijin Financing Guarantee Co.,Ltd. Pledgor: XI'AN TAIKOMED MEDICAL TECHNOLOGY Co.,Ltd. Registration number: Y2024980003898 |
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Granted publication date: 20210706 Pledgee: Xi'an Caijin Financing Guarantee Co.,Ltd. Pledgor: XI'AN TAIKOMED MEDICAL TECHNOLOGY Co.,Ltd. Registration number: Y2024980003898 |