KR20150031210A - Pharmaceutical composition for pulp revasularization and apexogenesis comprising prolyl Hydroxylase Inhibitor or histone deacetylase inhibitor, and antibiotics, and synthetic polymer nano fiber mesh comprising the same - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for dental pulp regenerative therapy, comprising: at least one selected from a prolyl hydroxylase inhibitor and a histone deacetylase inhibitor; and antibiotics. The pharmaceutical composition for dental pulp regenerative therapy and apexification, comprising a prolyl hydroxylase inhibitor and/or a histone deacetylase inhibitor and antibiotics, and the synthetic polymer nanofiber mesh comprising the composition, of the present application, inhibit and alleviate inflammation caused by bacterial infection and simultaneously induce dental pulp regeneration and formation of root apex through revascularization of dental pulp tissues, and thus can be used for effective dental pulp regenerative therapy and apexification.

Description

The present invention relates to a pharmaceutical composition for regenerating dental restoration or induction of tooth root formation comprising a proline hydrolysis inhibitor or a histone deacetylase inhibitor and an antibiotic, and a pharmaceutical composition for pulp revasularization apexogenesis comprising prolyl hydroxylase inhibitor or histone deacetylase inhibitor, and antibiotics,

The present invention relates to a pharmaceutical composition for regenerating or inducing root regeneration comprising a prolyl hydroxylase inhibitor or a histone deacetylase inhibitor and an antibiotic, and a synthetic polymer nanofiber mesh comprising the same.

The pain and edema that arise from the necrosis of immature permanent teeth are the main causes of dental caries and dimensional exposures due to trauma commonly occurring in children and adolescents. It is also known to be caused by anatomic variations such as tooth and teeth in the process of tooth development, and the frequency is quite high. In the case of pulp necrosis in the immature permanent teeth, the endodontic treatment is expected in the case of a dental disease such as the immature permanent teeth. The endodontic treatment is the treatment for the dental and periapical diseases. Since then, the expenditure of the national health insurance medical care insurance has been placed in the 10th place of the disease. Most endodontic treatments have been reported to be cured with a success rate of around 90%, but necrotizing immature permanent teeth can not be easily resolved by conventional endodontic treatment and patients may suffer from long term pain or occasionally tooth extraction Is an unpredictable therapeutic target.

Recent revascularization techniques have been introduced for the treatment of immature permanent teeth, and have received great attention in the field of endodontic treatment. Although successful clinical trials have been reported for many years, the results of treatment are limited to empirical treatment and most clinical cases, and the predictability of the prognosis is low, as well as the aftereffects of tooth discoloration after treatment Etc., have not been confirmed. There is no general recommendation that the guideline of regenerative endodontic treatment is not available at present.

In this regard, the present inventors have recently shown that a locally applied prolyl hydroxylase inhibitor or histone deacetylase inhibitor has an effect of promoting angiogenesis and hard tissue regeneration (Korean Patent No. 1359571, Korean Patent Application No. 2013 -0093822), nanofibers that can also be used as delivery materials for low-molecular weight drugs have been shown to exhibit dentin-cell differentiation and dentin-dental composite regeneration effects (Korean Patent No. 1370023) There is a need for an effective treatment and / or induction method.

Under these circumstances, the present inventors have made intensive efforts to develop drugs for regenerating dental pulp or root induction, and as a result, have found that a prochlorhydrogylase inhibitor or a histone deacetylase inhibitor incorporated in a synthetic polymer nanofiber mesh, It has been confirmed that the combination of antibiotics is very effective for regenerative therapy or root induction induction therapy, and the present invention has been accomplished.

The present invention provides a pharmaceutical composition comprising at least one inhibitor selected from a prolyl hydroxylase inhibitor and a histone deacetylase inhibitor; And an antibiotic, and a synthetic polymer nanofiber mesh comprising the same, and a method for promoting the regeneration of dimensions and induction of root formation using the pharmaceutical composition and the synthetic polymer nanofiber mesh .

Hereinafter, the present invention will be described in detail.

In one aspect for the above object, the present invention provides a method for regenerating a dental root or inducing root formation comprising an antibiotic and at least one inhibitor selected from a pyrrolyl hydroxylase inhibitor and a histone deacetylase inhibitor A pharmaceutical composition is provided.

Prolyl Hydroxylase Inhibitors (PHIs) used in the present invention are compounds that regulate HIFs to function in hypoxic conditions by destroying Hypoxia-Induced Factors (HIFs), which are continuously produced in cells, at normal oxygen partial pressures It is a low-molecular-weight drug that inhibits rheylhydroxylase. (HIFs), Heme Oxygenase 1 (HO1), Erythropoietin, Inducible Nitric Oxide Synthase (iNOS), and Glut1, which are under the control of HIFs, VEGF, and the like. The prolyl hydroxylase inhibitor may be, for example, dimethyloxalylglycine (DMOG), desferrioxamine (DFO), or L-mimosine (L-mim).

Histone deacetylase (HDAC) used in the present invention means an enzyme that deacetylates histone. The chromatin structure of histone proteins is regulated by chemical modifications such as acetylation, and the degree of chromatin structure, or DNA loosening, affects transcription from DNA to mRNA. The acetylation of histone proteins is regulated by the action of histone acetyltransferases and histone deacetylase. &Quot; HDAC inhibitors " perform hyperacetylation of histones and effect a change in gene expression. The histone deacetylase inhibitor may be selected from, for example, hydroxamic acid, cyclic tetrapeptide, depsipeptides, benzamide, electrophilic ketone, Valproic acid, and butyrate.

In addition, the antibiotic used in the present invention includes all drugs which inhibit the growth of germs which may be accompanied by the size and apophysis, and the bacterium is preferably Gram-positive bacteria or Gram-negative bacteria. Such antibiotics include, for example, beta-lactam antibiotics (penicillin, ampicillin, amoxicillin, diclofacrine, cephalexin and other penicillins and cephalosporin derivatives), vancomycin, amphotericin, polyamicin, ketoconazole, fluconazole, itraconazole , Aminoglycosides, tetracyclines, macrolides, rinkosamides, chloramphenicol, rifampin, quinolone antibiotics (malic acid, sifloxacin), sulfamic antibiotics (sulfonamides, trimethoprim), metronidazole, minocycline, It can be Korean.

The pharmaceutical composition may contain a prolyl hydroxylase inhibitor or a histone deacetylase alone, but preferably both a prolyl hydroxylase inhibitor and a histone deacetylase. Also as a preferred embodiment, the prolyl hydroxylase inhibitor and the histone deacetylase may be contained in the nanocapsules. The nanocapsule is capable of controlling the drug glass. The nanocapsule can be used to control the drug glass. The nanocapsules can be prepared by taking into account the spread of inflammation from the apical region to the bone marrow due to bacterial infection of the dental tissue, Can be made advantageous at an appropriate point in time. The nanocapsules used in the present invention are particles having a size of several tens to several thousands of nanometers including the drug, such as polycaprolactone, poly (ε-caprolactone), polylactic acid polylactic acid, polyglycolic acid, polyvinic acid, and chitosan. The polymer may be prepared by dissolving at least one synthetic polymer selected from the group consisting of polyglycolic acid, polyglycolic acid, polyglycolic acid, polylactic acid, polyglycolic acid, polyvinal acid and chitosan.

The composition of the present invention includes, in addition to the above-described effective ingredients for administration, at least one pharmaceutically acceptable carrier. In the present invention, the term "pharmaceutically acceptable carrier" means a known pharmaceutical excipient that is useful when formulating a pharmaceutically active compound for administration and is substantially non-toxic and non-sensitive under the conditions of use. The exact ratio of such excipients is determined by standard pharmaceutical practice, as well as the solubility and chemical properties of the active compound, the route of administration chosen.

Formulations of the pharmaceutical compositions and pharmaceutically acceptable carriers can be appropriately selected according to techniques known in the art and can be found, for example, in the following references: [Urquhart et al., Lancet, 16: 367, 1980 ]; [Lieberman et al., PHARMACEUTICAL DOSAGE FORMS-DISPERSE SYSTEMS, 2nd ed., Vol. 3, 1998]; [Ansel et al., PHARMACEUTICAL DOSAGE FORMS & DRUG DELIVERY SYSTEMS, 7th ed., 2000]; [Martindale, THE EXTRA PHARMACOPEIA, 31st ed.]; [Remington ' s PHARMACEUTICAL SCIENCES, 16th-20th editions]; [THE PHARMACOLOGICAL BASIS OF THERAPEUTICS, Goodman and Gilman, eds., 9th ed., 1996]; [Wilson and Gisvolds' TEXTBOOK OF ORGANIC MEDICINAL AND PHARMACEUTICAL CHEMISTRY, Delgado and Remers, eds., 10th ed., 1998].

The content of the prolyl hydroxylase inhibitor, the histone deacetylase and the antibiotic contained in the composition of the present invention can be appropriately determined depending on the kind of the inhibitor or the drug, the body weight, the age, sex, the health condition, , Excretion rate, and degree of severity of disease.

The present invention also provides a synthetic polymer nanofiber mesh containing the pharmaceutical composition.

The synthetic polymer nanofiber meshes may be fabricated to have various nanofiber diameters. Preferably, the toxic material of the upper dimensional filler (e.g., MTA, resin) is shielded from direct contact with the dimension and may have a nanofiber diameter capable of promoting differentiation into dentinal cells, more preferably, Of the fiber diameter. Particularly, when the diameter is 300 to 600 nm, the differentiation of the epithelial cells can be further promoted.

In addition, the synthetic polymer nanofiber mesh according to the present invention preferably has a 3D structure (scaffold). In tissue engineering, these 3D structures (scaffolds, artificial extracellular matrix) play an important role in the function of adsorption, migration, proliferation, differentiation of cells, and the formation of new tissue. In the case where such a synthetic polymer nanofiber mesh has a 3D structure, unlike the conventionally used nonwoven fabric type synthetic polymer, it provides an excellent 3D microenvironment, promotes cell attachment, proliferation and differentiation, and is effective The synergistic action with the pro-hydroxylase inhibitor, histone deacetylase, and antibiotics makes it possible to exert excellent dimensional regeneration treatment or to induce roots formation.

The mesoporous nanofiber meshes of the present invention can be used in a variety of applications such as polycaprolactone, poly (ε-caprolactone), polylactic acid, polyglycolic acid and chitosan ) Of at least one synthetic polymer selected from the group consisting of

In order to achieve the object of the present invention, a synthetic polymer nanofiber mesh having appropriate fiber diameter and fiber density capable of blocking toxic substances in direct contact blocking and hydration process of a dental filler by using the synthetic polymer can be prepared and used In the present specification, polyepsilon caprolactone was used as a preferable example.

Dissolution of the synthetic polymer may be carried out using a solvent selected from the group consisting of dimethylformamide, dichloromethane, tetrahydrofuran, chloroform, dioxane, ethanol, methanol, Propanol, and acetic acid. The solvent may be selected from the group consisting of methanol, ethanol, propanol, and acetic acid.

A method for producing the synthetic polymer nanofiber meshes known in the art for the production of the synthetic polymer nanofiber meshes can be used without limitation. Polymer solutions or melts with sufficient viscosity can form fibers when subjected to electrostatic forces, and can be fabricated from micrometers to nanometers using electrospinning technology.

The electrospinning process refers to a process of instantaneously spinning a polymer in a low viscosity state by a high voltage electrostatic force into a fiber form by applying an electrostatic force larger than a surface tension in the polymer. In the present invention, a synthetic polymer nanofiber mesh As a preferred example for the manufacture of the electrode, the electrospinning method was used.

In addition, the pharmaceutical composition containing the prolyl hydroxylase inhibitor, the histone deacetylase, and the antibiotic according to the present invention can be prepared by a known method such as encapsulation and application of the synthetic polymer nanofiber mesh prepared as described above .

The present invention relates to a pharmaceutical composition for regenerating dental restoration or root induction induction comprising a prodrug hydroxylase inhibitor or a histone deacetylase inhibitor and a pharmaceutical composition comprising an antibiotic and a synthetic polymer nanofiber mesh Inhibits and alleviates inflammation caused by bacterial infection, induces vascular remodeling, regeneration of dental tissues and root formation, and is very effective for effective regenerative therapy and treatment of dental diseases through the same. In the present specification, the dental disease may be one or more diseases selected from the group consisting of dental caries dimensional degeneration, dimensional necrosis, apical lesion, root apical formation, dental caries, and most preferably immature root apical lesion.

Accordingly, in another aspect, the present invention provides a method for promoting dimensional regeneration and induction of tooth root formation, comprising the step of placing the synthetic polymer nanofiber mesh in a dimension.

In one preferred embodiment, the method for promoting dimensional regeneration and induction of tooth root formation may further include positioning a mineral trioxide aggregate (MTA) in the synthetic polymer nanofiber mesh.

The MTA used herein is a hydrophilic fine powder which is cured within 4 hours when brought into contact with moisture and is used as a material for root canal treatment which is mainly composed of tricalcium silicate, tricalcium aluminate, tricalcium oxide and silicate oxide. The pH is known to be about 12.5 . When such an MTA is used, it is possible to induce reshaping of the dentin gypsum and enhance the therapeutic effect of the dental disease.

A pharmaceutical composition for regenerating or root induction induction therapy comprising a prolyl hydroxylase inhibitor or a histone deacetylase inhibitor of the present invention and an antibiotic, and a synthetic polymer nanofiber mesh containing the same, Inhibits and alleviates inflammation, and at the same time induces the regeneration of dental tissues or root formation, and thus can be used for the treatment of effective dental diseases and periapical diseases.

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a photograph of a micro-CT before and after treatment of beagle dog immature permanent tooth dental necrosis using the composition of the present invention. Fig.
FIG. 2 is a graph comparing dentin areas of a control group and an experimental group to which a synthetic polymer nanomask containing a pharmaceutical composition according to the present invention was applied.
FIG. 3 is a graph comparing dentin thicknesses between a control group and an experimental group to which a synthetic polymer nanomask containing a pharmaceutical composition according to the present invention was applied.
FIG. 4 is a graph comparing root lengths of a control group and an experimental group to which a synthetic polymer nanomask containing a pharmaceutical composition according to the present invention was applied.
FIG. 5 shows apical papilla cells obtained by primary culture of beagle dog immature permanent tooth root apical tissues after cell culture on nanofiber mesh incorporated with low molecular weight drug and antibiotic prepared in Preparation Example 1, And the degree of expression.
FIG. 6 shows apical papilla cells obtained by primary culture of beagle dog immature peritoneal root apex tissues after cell culture on nanofiber mesh incorporated with low molecular weight drugs and antibiotics prepared in Preparation Example 1, As shown in Fig.

Hereinafter, the present invention will be described in more detail with reference to examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.

Manufacturing example  One: Ploll Hydroxylase  Inhibitor or Histone Deacetylase  Synthetic Polymers Containing Inhibitors, and Antibiotics Nanofiber mesh  making

A synthetic polymer nanofiber mesh having a low molecular weight drug, a prolyl hydroxylase inhibitor and / or a histone deacetylase inhibitor and an antibiotic, was prepared. Such synthetic polymer nanofiber meshes should be adjusted so that effective concentrations of the drug are released at appropriate times, considering the proliferation of the periapical infections due to bacterial infection of the dental tissue and a series of progress / healing processes in which the surrounding tissues are destroyed . For this purpose, low molecular weight drugs were encapsulated in nanocapsules to control the drug glass. Antibiotics are coated on nanofiber meshes for drug treatment of bacterial infections of dimensions and apophysis and embolization of prolyl hydroxylase inhibitors and / or histone deacetylase inhibitors into nanofiber meshes Or encapsulated in nanocapsules. It is intended that the prodrug hydroxylase inhibitor and / or the histone deacetylase inhibitor be slowly and continuously released over time in antibiotic glass.

Specifically, to prepare a synthetic polymer nanofiber mesh, poly (ε-caprolactone) (hereinafter referred to as PCL) fiber matrix was mixed with dichloromethane (MC) and dimethylformamide (DMF) DMF) was prepared by electrospinning using a 10% (w / v) PCL solution mixed at 4: 6. More specifically, PCL was dissolved in MC. After the PCL was completely dissolved, DMF was added to the PCL-MC solution and then shaken gently. DMOR and butyrate were added to the PCL solution by previously dissolving the dimethylhydroxylase inhibitor dimethyloxalylglycine (DMOG) and the histone deacetylase inhibitor Butyrate in DMF. The prepared PCL solution was poured into a syringe of 10 mm using a stainless steel syringe needle (27G) and electrospinning was carried out on the methanol water tank which is a drum collector. The potentials and distances to the collector were 15 kV and 10 cm, respectively. For subsequent use in experiments, the PCL-nanofiber meshes were cut and stored in a dryer. In addition, antibiotics (Ciprofloxacin, Minocycline, Metronidazole) were dissolved in sterilized distilled water at saturating concentrations, and the fabricated nanofibers were immersed overnight and then lyophilized to apply antibiotics to the nanofibers.

Chitosan-TPP (tri-polyphosphate) was used to make nanocapsule particles containing DMOG or histone deacetylase inhibitor Butyrate as a pyrrolyl hydroxylase inhibitor. This method uses TPP as a polyanion, which utilizes the property of reacting with a polyvalent polyanion by intramolecular and intermolecular crosslinking mediated by polyanion of chitosan and instantly becoming a gel. 20 mg of purified low molecular weight chitosan (Chitosan, low molecular weight, 75-85% deacetylated: Aldrich) is dissolved in 30 ml of 2% acetic acid solution. DMOG and butyrate were added together in the course of making the chitosan solution. Prepare 30 mg of TPP dissolved in 10 ml of 2% acetic acid solution. The prepared chitosan solution and TPP solution are mixed and agitated slowly for one hour using an agitator. When mixed slowly with a pipette, TPP starts ionic cross-linking and coacervation, and chitosan-TPP nanoparticles are formed. It is divided into a cornical tube, sonicated for 5 times, and centrifuged at 1500 rpm for 3 minutes. The supernatant is discarded and washed with distilled water twice. They were kept in the freezer for one day and then lyophilized.

Manufacturing example  2: Immature permanent tooth Dimensional necrosis  Setting up an animal model

In the beagle dogs (male, 4 ~ 5 months old), the vagina was exposed to the immature permanent anterior teeth without apical root formation, and the surrounding teeth were inoculated into the cavity and filled with composite resin. After 7 weeks of vaginal formation, root canal lesions were confirmed by radiography and an animal model was established by applying the composition of the present invention prepared in Preparation Example 1

Example  One: Beagle dog Immature permanent tooth  Validation of Applied Composition of the Invention

As a control group, non-treatment group and conventional therapy treatment group were set up. Conventional treatment groups treated with 3-mix (Ciprofloxacin, Minocycline, Metronidazole) and calcium hardoxide paste. In addition, a group treated with the nanofiber mesh incorporated with the low molecular weight drug and the antibiotic prepared in Preparation Example 1 was set as an experimental group. At 8 weeks after treatment, all animals were sacrificed and jaws of the corresponding teeth were collected. MicroCT and histomorphological tests were performed on the collected samples (Fig. 1). Among the reconstructed Micro-CT slices, images parallel to the long axis of the tooth including the root were selected and the area, thickness, and root length of the root dentin were measured and compared using image measurement software (Image J) ). As shown in FIG. 1, in the treatment group according to the conventional treatment method, the thickness of the dentin was very thin, the length of the root was short, and the deviation was large due to the dimensional damage. It was confirmed that when the synthetic polymer nanofiber mesh containing the pharmaceutical composition according to the present invention was applied similarly to the pattern observed in the non-treated group in which no damage was caused, the dentin thickness and the root length were remarkably increased have. 2 to 4, the dentin area of the root is about 80% (Fig. 2), the dentin thickness of the root is about 30% (Fig. 3), and the length of the root is also about 30% It was confirmed that when the pharmaceutical composition according to the present invention and the nanofiber mesh were treated, excellent dimensional regeneration effect was exhibited.

Example  2: Beagle dog Immature permanent tooth  In periapical tissues Primary culture  Validation of the composition of the present invention in cell culture

The apical papilla cells obtained by primary culturing of the apical tissue of beagle dog immature permanent tooth lesion were cultured on the nanofiber mesh incorporated with the low molecular weight drug and antibiotic prepared in Preparation Example 1, 5) and expression of differentiation markers of dAb (FIG. 6) were evaluated using Western analysis and real-time PCR analysis, respectively. VEGF was identified as an inducer of angiogenesis and DSPP (dentin sialophosphoprotein) as an indicator of dAb differentiation. As a result, as shown in FIG. 5, it was confirmed that the expression of angiogenesis-inducing factors was increased in proportion to the concentration of DMOG contained in the pharmaceutical composition according to the present invention. Further, as shown in FIG. 6, a group treated with only PCLF as a synthetic polymer nanofiber mesh, a group treated with PCLF as a pyrrolyl hydroxylase inhibitor and a group treated with butyrate as a histone deacetylase inhibitor, and DML And PCLF at the same time showed an excellent DSPP expression effect at least twice as much as that of the control group. Particularly, in the group treated with DMOG and PCLF at the same time, the group exhibiting a remarkable effect of DSPP expression of about 5.5 times or more was confirmed to exhibit excellent dimensional regeneration effect when the pharmaceutical composition and the nanofiber mesh according to the present invention were treated I could.

Claims (18)

At least one inhibitor selected from the group consisting of prolyl hydroxylase inhibitor and histone deacetylase inhibitor; And an antibiotic. The pharmaceutical composition according to claim 1, wherein the prolyl hydroxylase inhibitor is selected from the group consisting of dimethyloxalylglycine (DMOG), desferrioxamine (DFO), and L-mimosine (L-mim) Lt; RTI ID = 0.0 > regenerative < / RTI > therapy. The histone deacetylase inhibitor of claim 1, wherein the histone deacetylase inhibitor is selected from the group consisting of hydroxamic acid, cyclic tetrapeptide, depsipeptides, benzamide, electrophilic ketone ), Valproic acid, and butyrate. ≪ Desc / Clms Page number 14 > The antibiotic according to claim 1, wherein the antibiotic is selected from the group consisting of a betalactam antibiotic, vancomycin, amphotericin, polyamicin, ketoconazole, fluconazole, itraconazole, aminoglycoside, tetracycline, macrolide, rinkosamide, chloramphenicol, rifampin, quinolone antibiotic , Sulfamic antibiotics, metronidazole, minocycline, and pyrimethamine. The pharmaceutical composition according to claim 1, wherein the prochlorhydrogylase inhibitor, the histone deacetylase inhibitor or the antibiotic is encapsulated in nanocapsules. At least one inhibitor selected from the group consisting of a prolyl hydroxylase inhibitor and a histone deacetylase inhibitor; And a pharmaceutical composition for inducing root formation comprising an antibiotic. 7. The method of claim 6, wherein the prolyl hydroxylase inhibitor is selected from the group consisting of dimethyloxalylglycine (DMOG), desferrioxamine (DFO), and L-mimosine (L-mim) Lt; RTI ID = 0.0 > roots. ≪ / RTI > 7. The method of claim 6, wherein the histone deacetylase inhibitor is selected from the group consisting of hydroxamic acid, cyclic tetrapeptide, depsipeptides, benzamide, electrophilic ketone ), Valproic acid, and butyrate. ≪ RTI ID = 0.0 > 11. < / RTI > The antibiotic according to claim 6, wherein the antibiotic is selected from the group consisting of a betalactam antibiotic, vancomycin, amphotericin, polymyxin, ketoconazole, fluconazole, itraconazole, aminoglycoside, tetracycline, macrolide, rinkosamide, chloramphenicol, rifampin, quinolone antibiotic , Sulfamic antibiotics, metronidazole, minocycline, and pyrimethamine. [Claim 7] The pharmaceutical composition according to claim 6, wherein the prolyl hydroxylase inhibitor, the histone deacetylase inhibitor or the antibiotic is encapsulated in nanocapsules. A pharmaceutical composition comprising at least one inhibitor selected from the group consisting of a prolyl hydroxylase inhibitor and a histone deacetylase inhibitor and an antibiotic, Nanofiber meshes. The synthetic polymer nanofiber mesh according to claim 11, wherein the synthetic polymer nanofiber mesh has a 3D structure. 12. The method of claim 11, wherein the synthetic polymer nanofiber mesh is selected from the group consisting of polycaprolactone, poly (ε-caprolactone), polylactic acid, polyglycolic acid, ; And at least one synthetic polymer selected from the group consisting of chitosan, and a synthetic polymer nanofiber mesh. The synthetic polymer nanofiber mesh according to claim 11, which has a diameter of 100 to 1100 nm. 14. A method of promoting dimensional regeneration and induction of tooth root formation comprising the step of placing a synthetic polymer nanofiber mesh selected from any one of claims 11 to 14 in a dimension. 16. The method of claim 15, further comprising the step of placing a mineral trioxide aggregate (MTA) in the synthetic polymer nanofiber mesh on the synthetic polymer nanofiber mesh. The pharmaceutical composition according to claim 1, wherein the dental treatment is for a patient having dental disease. 18. The method according to claim 17, wherein the dental disease is at least one disease selected from the group consisting of dental caries of permanent and immature teeth, dimensional alteration, necrosis of size, apical lesion, and dental caries. .

Images