CN110548215A - Nasal cavity implant and application thereof - Google Patents
Nasal cavity implant and application thereof Download PDFInfo
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- CN110548215A CN110548215A CN201910912591.2A CN201910912591A CN110548215A CN 110548215 A CN110548215 A CN 110548215A CN 201910912591 A CN201910912591 A CN 201910912591A CN 110548215 A CN110548215 A CN 110548215A
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- implant
- nasal
- drug
- nasal implant
- main body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
- A61M31/002—Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2207/00—Methods of manufacture, assembly or production
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2210/00—Anatomical parts of the body
- A61M2210/06—Head
- A61M2210/0618—Nose
Abstract
the invention provides a nasal implant and applications thereof, the nasal implant comprising: a body including a connection end and a free end; the connecting end includes at least one engagement member and a rounded terminal end; towards the direction from the connecting end to the free end of the main body, the included angle between the surface of the engagement part closest to the main body and the outer wall surface of the main body is alpha, and is more than or equal to 10 degrees and less than or equal to 90 degrees; when the nasal implant is implanted into nasal tissues, the nasal implant has better engaging capacity with the nasal tissues on the premise of ensuring better slow-release effect (slow steady-state release of the medicine can be realized, and efficient treatment effect can be achieved by adopting smaller dose), and can be prevented from being discharged out of the body together when sneezing or rhinorrhea occurs.
Description
Technical Field
The invention belongs to the field of medical appliances, and relates to a nasal cavity implant and application thereof.
background
The main clinical manifestations of allergic rhinitis are sneezing, several paroxysmal attacks each day, more than 3, and foreign articles report that a sneezing generally has a speed of 150 km/h, i.e. 41.7 m/s, and can be splashed out of three or four meters, almost close to the central wind force of 15-stage typhoon. In general, the administration is carried out through the nasal cavity or nasal passage, but such administration is not effective for treating sneezing or rhinorrhea.
CN101574507B discloses a nasal cavity drug delivery system for treating headache, which comprises a nasal inhaler and a drug composition, wherein the nasal inhaler comprises an elastic support and a drug-carrying member arranged at the end of the elastic support, the elastic support is a solid support or a hollow support, the drug composition comprises an active ingredient with a therapeutically effective amount and a pharmaceutically acceptable carrier, and the active ingredient is prepared from the following raw material drugs in parts by weight: 30-45 parts of ginger, 30-45 parts of radish seed, 0.1-0.5 part of artificial musk, 6-30 parts of menthol and 2-20 parts of borneol. The nasal administration system for treating headache has remarkable treatment effect on headache diseases, has no toxic or side effect, can improve the problem that nasal mucosa is difficult to adhere when common nasal drops or nasal sprays are administered, but is difficult to avoid the phenomenon that the administration system is discharged out of the body when sneezing or snivel occurs, thereby influencing the treatment effect.
CN101884818A discloses an inhalation type drug delivery system, which comprises drug carrier particles, active ingredients of drugs and a drug delivery device. Effective medicinal components can be loaded on 0.5-10 micron medicinal carrier particles, and the medicinal powder particles are effectively conveyed to specific parts of a human body, such as nasal cavities, bronchus, lung and the like, through a medicament conveying device, such as a dry powder inhaler, so as to achieve the aim of treating diseases.
Therefore, it is highly desirable to provide a nasal implant that has a good therapeutic effect, and that can engage the nasal mucosa well and is not expelled from the body during sneezing or nasal discharge.
Disclosure of Invention
The invention aims to provide a nasal cavity implant and application thereof, wherein the nasal cavity implant has better engaging capacity with nasal cavity tissues on the premise of ensuring better slow-release effect (slow and steady release of medicine can be realized, and high-efficiency treatment effect can be achieved by adopting smaller dose) when being implanted into the nasal cavity tissues, and can avoid being discharged out of the body together when sneezing or rhinorrhea occurs.
In order to achieve the purpose, the invention adopts the following technical scheme:
it is an object of the present invention to provide a nasal implant comprising:
A body including a connection end and a free end;
The connecting end includes at least one engagement member and a rounded terminal end;
the angle between the face of the engagement member closest to the body and the outer wall surface of the body is α, 10 ° ≦ α ≦ 90 °, such as 10 °, 20 °, 30 °, 40 °, 50 °, 60 °, 70 °, 80 °, 90 °, or the like, in the direction from the attachment end to the free end of the body.
The nasal implant can realize slow steady release of the medicine when being implanted into nasal tissues, can achieve high-efficiency treatment effect by adopting smaller dosage, has better engaging capacity with the nasal tissues, and can avoid being discharged out of the body together when sneezing or snivel flows.
The connecting end comprises at least one engaging part and a fillet terminal, wherein the surface of the engaging part far away from the main body and the fillet terminal can be directly and continuously connected or not, and the continuous connection refers to that: the surface of the engaging part far away from the main body and the outer surface of the connecting end of the main body are intersected to form an intersected point or surface, and the intersected point or surface is positioned on the circular arc of the rounded terminal; by not directly continuous, it is meant that the face of the engagement member remote from the body and the outer surface of the body connecting end intersect to form an intersection point or face, which is also a partial distance from the rounded terminus.
when the included angle alpha between the surface of the engaging part closest to the main body and the outer wall surface of the main body is 10-90 degrees, the implant is conveniently implanted into nasal cavity tissues, and under the reaction force (sneezing or rhinorrhea), the engaging part can tightly engage the tissues, so that the implant is prevented from falling off and being discharged; if the surface of the meshing part closest to the main body is an arc surface, the closest surface of the meshing part to the main body is a tangent plane, and if the closest surface of the meshing part to the main body is an edge ridge line, the included angle alpha is the included angle between the edge ridge line and the outer wall surface of the main body.
in the invention, the surface of the engaging part far away from the main body is continuously connected with the terminal of the fillet, so that the stress concentration can be avoided when the implant is implanted into tissues, and the damage of nasal mucosa caused when the implant is implanted into nasal cavity tissues can be effectively avoided. If the surface of the engaging member away from the body is an arc surface, the surface of the engaging member away from the body is a tangent plane.
In the present invention, the body is shaped as a cylinder.
In the present invention, the diameter of the cylinder is 0.05 to 0.8mm, for example, 0.05mm, 0.1mm, 0.15mm, 0.2mm, 0.25mm, 0.3mm, 0.35mm, 0.4mm, 0.45mm, 0.5mm, 0.55mm, 0.6mm, 0.65mm, 0.7mm, 0.75mm, 0.8mm, etc.
It is preferred in the present invention that the body is cylindrical in shape to avoid damage to nasal tissue when the implant is implanted within the nasal tissue.
The surface of the engaging part far away from the main body is continuously connected with the rounded terminal, and the engaging part and the main body can be integrally formed through a hot bending technology, so that the process cost is reduced.
in the present invention, α is 20 to 70 °, for example, 20 °, 30 °, 40 °, 50 °, 60 °, 70 °, and the like. In the present invention, the engaging member is of a tapered configuration, preferably a conical configuration.
In the present invention, an angle between a surface of the engaging member closest to the body and an outer wall surface of the body is α, which is exemplarily shown as follows: the engaging part is a regular oblique cone, and a generatrix of the oblique cone closest to the surface of the main body forms an included angle with the outer surface of the main body.
In the present invention, the cone angle of the conical structure is β, 2 ° ≦ β ≦ 50 °, such as 2 °, 5 °, 10 °, 15 °, 20 °, 25 °, 30 °, 35 °, 40 °, 45 °, 50 °, etc., preferably 5 ° ≦ β ≦ 30 °.
When α and β are chosen in the appropriate combination: alpha is more than or equal to 20 degrees and less than or equal to 70 degrees and/or beta is more than or equal to 2 degrees and less than or equal to 50 degrees, so that the nasal implant has proper hanging force after being implanted into nasal tissues, and the engaging capability of the nasal implant is improved.
In the invention, the conical structure is not a standard conical structure but an oblique conical structure, and when the cone angle of the oblique conical structure is 2-50 degrees, the sharpness and the deformation resistance of the cone angle can be ensured, so that the cone angle can conveniently penetrate into nasal cavity tissues and has better meshing effect with the tissues. When the taper angle is too high, the sharpness of the taper angle is reduced, so that the engagement effect is influenced; if the taper angle is too low, the deformation resistance of the taper angle may be affected, and thus the engagement effect may also be affected.
In the present invention, the maximum linear distance between any two points of the contact surfaces of the engaging member and the body is 10 to 200%, for example, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 120%, 150%, 160%, 180%, 200%, etc., preferably 50 to 150% of the diameter of the cylindrical body, and when the maximum linear distance between any two points of the contact surfaces of the engaging member and the body is 80 to 150% of the diameter of the cylindrical body, it is helpful to improve the hanging-down force.
In the present invention, the radius of the rounded corner of the engaging member connected to the body is 2 to 50% of the diameter of the cylinder, for example, 2%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, etc.
In the present invention, the main body and the engagement member of the nasal implant are of a one-piece construction.
In the present invention, the body of the nasal implant and the engagement member are removably connected.
In the invention, the main body and the engaging structure of the nasal implant can be an integral structure or can be connected in a detachable connection mode, and the main body and the engaging structure can be selected by a person skilled in the art according to actual needs.
in the present invention, the shape of the nasal implant includes any one of an anchor type, a T type, a J type, an umbrella type or an L type, and preferably any one of an anchor type, a J type or an umbrella type.
In the present invention, the nasal implant has a resistance to deformation of 2-20N, such as 2N, 5N, 7N, 10N, 12N, 15N, 17N, 20N, etc.
The anti-deformation force of the nasal implant is 2-20N, so that the implant has better anti-deformation capability when implanted into the nasal cavity, and has better engagement effect with tissues; when the deformation resistance of the implant is too low, the implant is easy to deform, and sneezing airflow can deform, stretch or straighten the implant, so that the meshing effect is influenced, and the implant is easy to spray out of the nasal cavity; when the deformation resistance of the implant is too high, discomfort can be brought to the nasal cavity, and the implant can be broken off under the action of external force, so that the service life of the implant is influenced.
In the present invention, the nasal implant comprises a biodegradable material and a drug.
In the present invention, the drug is dispersed in the biodegradable material; uniform dispersion is preferred.
in the present invention, the implant is formed by mixing and molding a biodegradable material and a drug.
In the invention, the implant is prepared in an integrated mode, namely, biodegradable materials and medicines are mixed, injected, extruded and molded to obtain the implant with a specific shape.
In the invention, the implant can be prepared by the integrated preparation, and the medicine can be effectively dissolved out along with the degradation of the biodegradable material, so that the effect of slow-release treatment is achieved.
in the present invention, the release period of the drug in the nasal implant is 30-75 days, such as 30 days, 35 days, 40 days, 45 days, 50 days, 55 days, 60 days, 65 days, 70 days, 75 days, etc.
in the present invention, the nasal implant has a daily release of 10-80 μ g of drug, for example 10 μ g, 20 μ g, 30 μ g, 40 μ g, 50 μ g, 60 μ g, 70 μ g, 80 μ g, etc.
In the invention, the medicine releases 10-80 mug medicine quantity every day, reaches the threshold value of action and lasts for 30-75 days to obtain a slow release system with stable release speed, little medicine action quantity and uniform release; in view of the safe amount of drug to be injected, the topical drug should be reduced to a safe amount according to the effective amount of drug, with the total amount of drug in the range of 300 μ g-6 mg.
According to the invention, the content of the biodegradable material and the medicament is adjusted, so that the medicament is slowly and uniformly released, and in addition, the release amount is small and stable, thereby achieving a better slow release effect.
In the present invention, the implant further comprises a hydrophilic polymer coating.
In the present invention, the hydrophilic polymer includes any one or a combination of at least two of starch, chitosan, gelatin, hyaluronic acid, collagen, polyglutamic acid, sodium alginate, cellulose and its derivatives, polyacrylamide, polyacrylic acid, polyvinylpyrrolidone, polyvinyl alcohol, polymaleic anhydride, polylactic acid, polyquaternium, or polyethylene glycol.
In the invention, the nasal cavity implant comprises an implant body and a drug coating layer arranged on the surface of the implant body.
in the invention, the implant can comprise an implant body and a drug coating, the shape of the implant body is the same as that of the implant, the drug coating can be coated on the surface of the whole implant body or can be coated partially, and the implant can be selected by a person skilled in the art according to the actual needs; preferably, the drug coating is applied to the outside of the body of the implant and the engagement assembly and continues to the inside part of the engagement assembly, so that the area of the implant contacting the tissue is maximally loaded with the drug.
in the invention, the implant body is made of biodegradable material.
In the present invention, the drug coating layer comprises a biodegradable polymer and a drug.
In the present invention, the range of selection of the material of the biodegradable polymer is the same as the range of selection of the biodegradable material.
in the present invention, the thickness of the drug coating layer is 0.001 to 1mm, for example, 0.001mm, 0.005mm, 0.01mm, 0.05mm, 0.11mm, 0.2mm, 0.3mm, 0.4mm, 0.5mm, 0.6mm, 0.7mm, 0.8mm, 0.9mm, 1mm, etc.
The drug loading of a single implant in the invention depends on the thickness of the drug coating, and the drug loading of the single implant is controlled by controlling the thickness of the drug coating to be 0.001-1 mm.
In the present invention, the drug coating is disposed on the surface of the implant in a coating manner.
In the present invention, the coating method includes any one of dipping, spinning, spraying, and brushing, and preferably spraying.
in the invention, the drug coating is formed by spraying the mixed solution of the biodegradable polymer and the drug on the surface of the implant after the mixed solution is atomized into particles.
in the invention, the drug coating is formed by atomizing the mixed solution of the biodegradable polymer and the drug into particles with the particle size of 50nm-500 μm and spraying the particles on the surface of the implant.
In the present invention, the mixed solution of the biodegradable polymer and the drug is atomized into fine particles having a particle size of 50nm to 500 μm and sprayed on the surface of the implant. Preferably, the atomized particles have a particle size of 10 to 500. mu.m. In other embodiments, the particles may be non-uniformly sized particles, but generally are within the size range, preferably the particles are normally distributed within the size range, and the atomization of the drug substance results in particles within a range other than a fixed value.
In the invention, the implant is obtained by processing the surface of the implant of the prefabricated product.
in the present invention, the treatment means includes any one of plasma treatment, swelling treatment, sand blasting treatment, sanding treatment, dermatoglyph treatment, electrostatic treatment, or wetting treatment, or a combination of at least two thereof.
In the present invention, the drug coating and the implant are linked together by crosslinking.
In the present invention, the crosslinking includes chemical crosslinking and physical crosslinking.
in the present invention, the chemical crosslinking includes polycondensation crosslinking or polyaddition crosslinking.
In the present invention, the physical crosslinking includes any one of photo-crosslinking, thermal crosslinking, radiation crosslinking, or natural crosslinking.
in the present invention, the method for preparing the implant may include: and coating the mixed solution of the biodegradable polymer and the medicine on the surface of the implant to obtain the implant.
The invention dissolves or uniformly disperses biodegradable polymer and medicine in solvent to form uniform solution, uses equipment to atomize the solution into uniform mixed solution particles, the atomized mixed solution particles have uniform particle size, the mixed solution particles with consistent size are sprayed on the surface of the prefabricated implant in a wet or semi-dry state, and a coating film is formed through crosslinking action.
Wherein the drug solution is obtained by dissolving the biodegradable polymer and the drug in a solvent.
In the present invention, the solvent includes water and/or an organic solvent.
In the present invention, the organic solvent includes any one or a combination of at least two of dichloromethane, chloroform, acetone, isopropanol, ethanol, tetrahydrofuran, hexafluoroisopropanol, hexafluoroacetone, dimethyl sulfoxide, acetonitrile, diethyl ether, ethyl acetate, n-hexane, pyridine, toluene, benzene, dimethylformamide, n-heptane, methanol, ethylamine, lactic acid, petroleum ether, glycerol, octanoic acid, n-hexanol, or cyclohexane.
In the present invention, the biodegradable material includes any one or a combination of at least two of chitosan, gelatin, algin, starch, hyaluronic acid, cellulose and its derivatives, polylactide-glycolide, polyglycolide, polylactic acid, L-polylactic acid, D-polylactic acid, polyvinyl alcohol, polyvinylpyrrolidone, polylactic acid-glycolic acid copolymer, polyethylene glycol, polycaprolactone, polyorthoester, polyglycolic acid, or polydioxanone.
In the present invention, the drug includes any one or a combination of at least two of aspirin, salicylic acid, diflunisal, salsalate, ibuprofen, indomethacin, flurbiprofen, phenoxyibuprofen, naproxen, piroxicam, phenylbutazone, fenprofen, fenbufen, carprofen, ketoprofen, diclofenac, ketorolac, tetrafluorofenamic acid, sulindac, tolmetin, celecoxib, aminoglycoside antibiotics, anti-adhesion and anti-scarring agents, macrolide antibiotics, cyclosporine a, berberine hydrochloride, paclitaxel, docetaxel, vinorelbine, elemene, or enalapril.
In the present invention, the aminoglycoside antibiotic includes any one or a combination of at least two of streptomycin, gentamicin, kanamycin, sisomicin, tobramycin, amikacin, netilmicin, nebivoxim, isepamicin, lividycin, micronomicin, paromomycin, neomycin, or aspartame.
in the present invention, the anti-adhesion and anti-scarring agent comprises glucocorticoid: triamcinolone acetonide, dexamethasone, betamethasone, cortisone, hydrocortisone, mometasone furoate, rimexolone, prednisone, prednisolone, methylprednisolone, triamcinolone, budesonide, beclomethasone dipropionate, fluticasone propionate, ciclesonide, fluocinolone, clobetasol, halometasone, difloron diacetate, halomethasone or fluocinolone acetonide, or a combination of at least two thereof.
In the invention, the macrolide antibiotics comprise any one or combination of at least two of erythromycin and derivatives thereof, azithromycin, midecamycin and derivatives thereof, spiramycin and derivatives thereof, acetylspiramycin, tacrolimus, sirolimus, everolimus, amphotericin B, pentamycin, fidaxomicin, telithromycin or mitomycin.
it is a further object of the present invention to provide a use of a nasal implant according to the first object in a drug delivery system.
In the invention, the nasal cavity implant is implanted into tissue by means of needle injection.
In the present invention, the application includes: the nasal implant is placed in the injection needle tube, the needle is inserted into the target position, the push rod is pushed, the nasal implant is implanted into the target position, and the engaging part is embedded into the nasal tissue.
in the present invention, the number of implants placed in the injection needle tube is 1-10, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10.
In the invention, the outer diameter of the injection needle tube is not higher than 18G.
In the present invention, the inner diameter of the injection needle tube is 0.8-1.0mm, such as 0.8mm, 0.85mm, 0.9mm, 0.95mm, 1.0mm, etc.
As is known in the art, nasal implants are required to be placed into a needle cannula, so the size of the implant is smaller than the size of the needle cannula.
Compared with the prior art, the invention has the following beneficial effects:
When the nasal implant is implanted into the nasal tissue, the nasal implant has better engaging capacity with the nasal tissue on the premise of ensuring better slow-release effect (slow steady release of the medicine can be realized, and high-efficiency treatment effect can be achieved by adopting smaller dose), and can avoid being discharged out of the body together when sneezing or rhinorrhea occurs.
Drawings
FIG. 1 is a schematic view showing the structure of an implant according to embodiment 1 of the present invention;
FIG. 2 is an enlarged view of a portion of FIG. 1;
FIG. 3 is a schematic view showing the structure of an implant according to example 4;
Wherein, 1 is a main body, 1-1 is a connecting end, 1-2 is a free end, 2 is an engaging component, 3 is a fillet terminal, h is the diameter of a cylinder, beta is a conical cone angle, and alpha is an included angle between a bus of the engaging component closest to the main body and the outer wall surface of the main body; r is a fillet radius.
Detailed Description
The technical solution of the present invention is further explained by the following embodiments. It should be understood by those skilled in the art that the examples are only for the understanding of the present invention and should not be construed as the specific limitations of the present invention.
example 1
This embodiment provides an implant, as can be seen in fig. 1 and 2, comprising a body 1 and an engagement member 2, the body 1 comprising a connecting end 1-1 and a free end 1-2, the connecting end 1-1 and the engagement member 2 of the body 1 being continuously contiguous with a rounded terminal end 3 on the side away from the body 1; wherein the main body 1 is cylindrical, and the diameter h of the cylinder is 0.5 mm; the engaging member 2 is conical in shape, the conical angle is beta, beta is 30 degrees; towards the direction from the connecting end 1-1 to the free end 1-2 of the main body 1, the included angle between the bus of the engaging part 2 closest to the main body 1 and the outer wall surface of the main body 1 is alpha, and alpha is 50 degrees; the maximum linear distance between any two points of the contact surface of the engaging member 2 and the main body 1 is 80% of the diameter of the cylinder, namely 0.4 mm; the radius R of a fillet 3 connecting the engaging part 2 and the main body 1 is 20 percent of the diameter of the cylinder, namely 0.1 mm; the number of the engaging members 2 is 1.
The preparation method of the implant in the embodiment comprises the following steps:
Mixing 10g of polylactic acid-glycolic acid copolymer of biodegradable material and 2g of aspirin of medicine uniformly by a melting and stirring method, injecting into a mould matched with the type of the implant, and carrying out hot pressing to obtain the implant.
The implant obtained in the embodiment is subjected to a tensile force deformation resistance test in a simulated human tissue to obtain that the deformation resistance of the implant is 8N, and the implant obtained in the embodiment is in a barb shape, so that the barb can be well meshed with the tissue under the action of a reaction force (sneezing or rhinorrhea), and is prevented from being discharged under the action of an external force.
Calculating the content of aspirin in an implant to be 0.5mg according to the volume of the implant, wherein the calculation method comprises the following steps: the content of aspirin in one implant (mass of aspirin × volume of one implant)/total volume of the implant, and drug dissolution of the sample in PBS solution at 37 ℃ by a drug dissolution tester, and the amount of the dissolved drug measured by HPLC, it was found that the average daily drug release rate was about 15 μ g.
Example 2
the present embodiment provides an implant comprising a body and an engagement member, the body comprising a connecting end and a free end, a face of the engagement member distal from the body being contiguous with a rounded terminal end; wherein the main body is in the shape of a cylinder, and the diameter h of the cylinder is 0.8 mm; the engaging part is conical, the conical angle is beta, and beta is 5 degrees; towards the direction from the connecting end to the free end of the main body, the included angle between the bus of the meshing part closest to the main body and the outer wall surface of the main body is alpha, and the alpha is 20 degrees; the maximum linear distance between any two points of the contact surface of the engaging part and the main body is 50 percent of the diameter of the cylinder, namely 0.4 mm; the radius of a fillet connecting the engaging part and the main body is 50 percent of the diameter of the cylinder, namely 0.4 mm; the number of the engaging members is 1.
The preparation method of the implant in the embodiment comprises the following steps:
(1) Uniformly mixing 1g of the biodegradable material polycaprolactone and 9g of the polylactic acid by a melting and stirring method, and preparing an implant according to the shape of the implant;
(2) Dissolving 600mg of polylactic acid, 200mg of medicine aspirin and 300mg of medicine mometasone furoate in 60ml of acetone to obtain medicine mixed solution;
(3) Treating the implant obtained in the step (1) with plasma for 30s, atomizing the medicine mixed liquid obtained in the step (1) into particles with the particle size of 500nm-50 microns by using tooling equipment, uniformly spraying the particles on the surface of the treated implant, performing air blowing and semi-drying in the spraying process, and drying in a drying oven at 40 ℃ for 30min after complete spraying to completely volatilize acetone to obtain the implant.
The implant obtained in this example was tested for tensile and deformation resistance in simulated human tissue in the same manner as in example 1, and the implant obtained in this example was in the shape of a barb, which was able to better engage with tissue and avoid expulsion under external force when subjected to a reaction force (sneezing or rhinorrhea).
The sample is subjected to drug dissolution in PBS solution at 37 ℃ by a drug dissolution tester, and the amount of the dissolved drug is tested by HPLC, so that the average daily release amount of aspirin is 10 mug, and the average daily release amount of mometasone furoate is 20 mug.
Example 3
This embodiment provides an implant comprising a body comprising a connecting end and a free end, and an engagement member having a face distal from the body that is contiguous with a rounded terminal end; wherein the main body is in the shape of a cylinder, and the diameter h of the cylinder is 0.05 mm; the engaging part is conical, the conical angle is beta, and the beta is 50 degrees; towards the direction from the connecting end to the free end of the main body, the included angle between the bus of the meshing part closest to the main body and the outer wall surface of the main body is alpha, and alpha is 70 degrees; the maximum linear distance between any two points of the contact surface of the engaging part and the main body is 100 percent of the diameter of the cylinder, namely 0.05 mm; the radius of a fillet connecting the meshing part and the main body is 2 percent of the diameter of the cylinder, namely 0.001 mm; the number of the engaging members is 1.
The preparation method of the implant in the embodiment comprises the following steps:
(1) Uniformly mixing 2g of biodegradable material polylactic acid and 200mg of drug mometasone furoate by a melting and stirring method, injecting into a mold, and carrying out hot pressing to obtain a core layer;
(2) dissolving 500mg of biodegradable material polyvinylpyrrolidone in 60mL of water to obtain cortex mixed solution;
(3) And (3) placing the core layer obtained in the step (1) in the cortex mixed solution obtained in the step (2), dipping and airing to obtain the implant.
The implant obtained in this example was tested for tensile and deformation resistance in simulated human tissue in the same manner as in example 1, and the implant obtained in this example was barb-shaped, so that the barb could be engaged with the tissue well under the reaction force (sneezing or rhinorrhea) to prevent the implant from being expelled by the external force.
Calculating the content of aspirin in an implant to be 0.8mg according to the volume of the implant, wherein the calculation method comprises the following steps: the mometasone furoate content in one implant (mass of mometasone furoate x volume of one implant)/total volume of the implant; the sample is dissolved in PBS solution at 37 ℃ by a drug dissolution tester, and the amount of the dissolved drug is tested by HPLC, so that the average release amount of mometasone furoate per day is 18 mu g.
example 4
this embodiment provides an implant, as shown in fig. 3, differing from example 1 only in that: the number of engaging elements was 2, and the rest of the composition was the same as in example 1.
the implant in this example was prepared in the same manner as in example 1.
The implant obtained in this example was tested for tensile and deformation resistance in simulated human tissue in the same manner as in example 1, and the implant obtained in this example was 18N in deformation resistance, and was barb-shaped, so that the barb could be engaged with the tissue well under the reaction force (sneezing or rhinorrhea) to prevent the implant from being expelled due to the external force.
Calculating the content of aspirin in an implant to be 0.6mg according to the volume of the implant, wherein the calculation method comprises the following steps: the content of aspirin in one implant (mass of aspirin × volume of one implant)/total volume of the implant, and drug dissolution of the sample in PBS solution at 37 ℃ by a drug dissolution tester, and the amount of the dissolved drug measured by HPLC, it was found that the average daily drug release rate was about 20 μ g.
Comparative example 1
the only difference from example 1 is that the implant does not include an engagement member, and the rest of the composition and the manufacturing method are the same as those of example 1.
As is clear from comparison between example 1 and comparative example 1, when the implant does not include the engaging member, the implant is implanted into the tissue, and the engaging strength with the tissue is extremely low, and the implant is easily discharged with sneezing and rhinorrhea.
comparative example 2
The only difference from example 1 is that α is 5 °, and the rest of the composition and the preparation method are the same as those of example 1.
It is understood from a comparison between example 1 and comparative example 2 that the implant is implanted into the tissue when α is low, and the engagement strength between the implant and the tissue is extremely low when the implant is subjected to a reaction force, and the implant is easily discharged with sneezing and rhinorrhea.
Comparative example 3
The only difference from example 1 is that α is 120 °, and the rest of the composition and the preparation method are the same as example 1.
As is clear from a comparison between example 1 and comparative example 3, when α is high, the implant is highly resistant to implantation into the tissue, and may damage the nasal cavity tissue, and when α is too high, the engagement strength between the implant and the tissue becomes low, and the implant is easily discharged with sneezing and rhinorrhea.
Comparative example 4
the only difference from example 1 is that β is 70 °, and the rest of the composition and the preparation method are the same as those of example 1.
As is clear from a comparison between example 1 and comparative example 4, when β is high, the sharpness of the implant is impaired, and the engaging strength with the tissue becomes low, and the implant is easily discharged with sneezing and rhinorrhea.
Comparative example 5
The difference from example 1 is only that the implant has a deformation resistance of 1N, and the rest of the composition and the manufacturing method are the same as example 1.
It is understood from the comparison between example 1 and comparative example 5 that when the deformation resistance of the implant is too low, deformation occurs when the implant is implanted into the tissue, and a good use effect cannot be achieved because the deformation resistance is too low to affect the engaging ability with the tissue.
in this embodiment, the injection member is implanted into the tissue by needle injection, and the specific method includes: the implant is placed in an injection needle tube, the needle is inserted into a target position, a push rod is pushed, the implant is implanted into the target position, and implantation of the implant is completed, wherein the outer diameter of the injection needle tube is not higher than 18G and mainly depends on the size of a human nasal cavity, the pulp of the injection needle tube is 0.8-1.0mm and mainly depends on the size of the implant, so that the model of the injection needle tube is not specifically limited, and a person skilled in the art selects a corresponding model or customizes the corresponding model according to actual needs.
The applicant declares that the above description is only a specific embodiment of the present invention, but the scope of the present invention is not limited thereto, and it should be understood by those skilled in the art that any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope of the present invention are within the scope and disclosure of the present invention.
Claims (10)
1. A nasal implant, comprising:
a body including a connection end and a free end;
The connecting end includes at least one engagement member and a rounded terminal end;
towards the direction from the connecting end to the free end of the main body, the included angle between the surface of the engagement part closest to the main body and the outer wall surface of the main body is alpha, and alpha is more than or equal to 10 degrees and less than or equal to 90 degrees.
2. the nasal implant of claim 1, wherein a face of the engagement member distal from the body is contiguous with the rounded terminus;
Preferably, the body is cylindrical in shape;
Preferably, the diameter of the cylinder is 0.05-0.8 mm;
Preferably, said α is 20-70 °;
Preferably, the engagement member is of a tapered configuration, preferably a conical configuration;
Preferably, the cone angle of the conical structure is beta, 2 DEG-beta is less than or equal to 50 DEG, preferably 5 DEG-beta is less than or equal to 30 DEG;
Preferably, the maximum linear distance between any two points of the contact surfaces of the engaging member and the body is 10 to 200%, preferably 50 to 150%, of the diameter of the cylindrical body;
preferably, the radius of the rounded corner of the engagement member connected to the body is 2-50% of the diameter of the cylinder.
3. The nasal implant of claim 1 or 2, wherein the body and the engagement member of the nasal implant are of a unitary construction;
Preferably, the body of the nasal implant and the engagement member are by a detachable connection;
Preferably, the shape of the nasal implant comprises any one of an anchor type, a T type, a J type, an umbrella type or an L type, preferably any one of an anchor type, a J type or an umbrella type;
Preferably, the nasal implant has a resistance to deformation of 2-20N.
4. The nasal implant according to any one of claims 1-3, wherein the nasal implant comprises a biodegradable material and a drug;
preferably, the drug is dispersed in the biodegradable material;
Preferably, the release period of the drug in the nasal implant is 30-75 days;
preferably, the nasal implant has a daily release of drug of 10-80 μ g.
5. The nasal implant of claim 4, wherein the implant further comprises a hydrophilic polymer coating;
Preferably, the hydrophilic polymer comprises any one or a combination of at least two of starch, chitosan, gelatin, hyaluronic acid, collagen, polyglutamic acid, sodium alginate, cellulose and derivatives thereof, polyacrylamide, polyacrylic acid, polyvinylpyrrolidone, polyvinyl alcohol, polymaleic anhydride, polylactic acid, polyquaternium or polyethylene glycol.
6. The nasal implant according to any one of claims 1-3, wherein the nasal implant comprises an implant body and a drug coating disposed on a surface of the implant body;
Preferably, the implant body is made of biodegradable material;
Preferably, the drug coating comprises a biodegradable polymer and a drug;
Preferably, the drug coating has a thickness of 0.001 to 1 mm.
7. The nasal implant of claim 6, wherein the drug coating is disposed in a coated manner on the surface of the implant;
Preferably, the coating mode comprises any one of dipping, spinning, spraying or brushing, and spraying is preferred;
preferably, the drug coating is formed by spraying the mixed solution of the biodegradable polymer and the drug on the surface of the implant after the mixed solution is atomized into particles;
Preferably, the drug coating layer is formed by atomizing a mixed solution of the biodegradable polymer and the drug into fine particles having a particle size of 50nm to 500 μm and then spraying the fine particles on the surface of the implant.
8. the nasal implant according to any one of claims 1-7, wherein the biodegradable material comprises any one or a combination of at least two of chitosan, gelatin, algin, starch, hyaluronic acid, cellulose and its derivatives, polylactide-glycolide, polyglycolide, polylactic acid, L-polylactic acid, D-polylactic acid, polyvinyl alcohol, polyvinylpyrrolidone, polylactic-co-glycolic acid, polyethylene glycol, polycaprolactone, polyorthoester, polyglycolic acid, or polydioxanone;
Preferably, the drug comprises any one or a combination of at least two of aspirin, salicylic acid, diflunisal, salsalate, ibuprofen, indomethacin, flurbiprofen, phenoxyibuprofen, naproxen, piroxicam, phenylbutazone, fenprofen, fenbufen, carprofen, ketoprofen, diclofenac, ketorolac, tetrafluorofenamic acid, sulindac, tolmetin, celecoxib, aminoglycoside antibiotics, anti-adhesion anti-scarring agents, macrolide antibiotics, cyclosporine a, berberine hydrochloride, paclitaxel, docetaxel, vinorelbine, elemene, or enalapril;
Preferably, the aminoglycoside antibiotic comprises any one or a combination of at least two of streptomycin, gentamicin, kanamycin, sisomicin, tobramycin, amikacin, netilmicin, nebivoxim, isepamicin, lividycin, micronomicin, paromomycin, neomycin or aspartame;
Preferably, the anti-adhesion and anti-scarring agent comprises a glucocorticoid: triamcinolone acetonide, dexamethasone, betamethasone, cortisone, hydrocortisone, mometasone furoate, rimexolone, prednisone, prednisolone, methylprednisolone, triamcinolone, budesonide, beclomethasone dipropionate, fluticasone propionate, ciclesonide, fluocinolone, clobetasol, halometasone, difloron diacetate, halomethasone or fluocinolone acetonide;
Preferably, the macrolide antibiotics include any one or a combination of at least two of erythromycin and its derivatives, azithromycin, midecamycin and its derivatives, spiramycin and its derivatives, acetylspiramycin, tacrolimus, sirolimus, everolimus, amphotericin B, pentamycin, fidaxomycin, telithromycin or mitomycin.
9. Use of a nasal implant according to any one of claims 1-8 in a drug delivery system;
Preferably, the nasal implant is implanted in tissue by needle injection.
10. the application according to claim 9, wherein the application comprises: the nasal implant is placed in the injection needle tube, the needle is inserted into a target position, the push rod is pushed, the nasal implant is implanted into the target position, and the engaging part is embedded into nasal tissue;
Preferably, the number of the nasal cavity implants placed in the injection needle tube is 1-10;
Preferably, the outer diameter of the injection needle tube is not higher than 18G;
Preferably, the inner diameter of the injection needle tube is 0.8-1.0 mm.
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| CN201910912591.2A CN110548215A (en) | 2019-09-25 | 2019-09-25 | Nasal cavity implant and application thereof |
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| CN201910912591.2A CN110548215A (en) | 2019-09-25 | 2019-09-25 | Nasal cavity implant and application thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111035796A (en) * | 2019-12-26 | 2020-04-21 | 杭州维力医疗器械有限公司 | Drug-loaded hemostatic cotton with controllable degradation and preparation method thereof |
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Address after: Room 2206, building 1, 396 lishizhen Road, China (Shanghai) pilot Free Trade Zone, Pudong New Area, Shanghai, 201203 Applicant after: Puyi (Shanghai) Biotechnology Co.,Ltd. Address before: Room 2206, building 1, 396 lishizhen Road, China (Shanghai) pilot Free Trade Zone, Pudong New Area, Shanghai, 201203 Applicant before: PUYI (SHANGHAI) BIOTECHNOLOGY Co.,Ltd. |
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