KR102006071B1 - Micro-needles and method of mamufacture - Google Patents

Abstract

The microneedle according to the present invention comprises a needle portion having a sharp tip at its end, a protective portion provided on the surface of the needle portion at a room temperature and made of a material having a low solubility to water, And a chemical liquid part coated with the chemical liquid. According to this configuration, it is possible to suppress the deformation of the needle portion during the coating of the chemical liquid during the manufacturing process of the micro needle, thereby contributing to the improvement of the efficiency of the micro needle.

Description

[0001] MICRO-NEEDLES AND METHOD OF MAMUFACTURE [0002]

The present invention relates to a microneedle and a method of manufacturing the same, and more particularly, to a moisture-resistant microneedle containing a drug only at a tip portion penetrating into the skin, and a method of manufacturing the same.

Various drug delivery technologies have been used, including oral, intramuscular, transdermal, and mucosal delivery. Among them, the transdermal drug delivery technology is a technique of delivering drugs through the skin using patches, creams, etc., and it can avoid the metabolism by intestines, and it is advantageous that the drugs can be continuously administered through patches.

Typical transdermal drug delivery systems include passive transdermal drug delivery systems and active transdermal drug delivery systems. A passive transdermal drug delivery system is a passive method that depends on the physicochemical properties of the drug and is applied to the skin in the form of a cream, a patch, and an ointment. On the other hand, this passive transdermal drug delivery system has limitations only when the molecular weight of the drug delivered through the skin is 500 Da or less.

In addition, an active transdermal drug delivery system physically permeates a 10 μm thick stratum corneum using a micro needle to overcome the skin permeation limit, thereby transferring an effective ingredient. These active transdermal drug delivery systems include creamed solid micro needles, coated micro-needles coated with active ingredient, water-soluble molten micro-needles, and hollow micro needles sized from conventional syringes.

On the other hand, among the microneedles, the molten microneedles have disadvantages such as long manufacturing time, difficulty in supplying a fixed amount of drug, restriction of the transferring material, and deformation due to moisture in the air. However, , Strong resistance to mechanical strength change, and a glass for supplying a fixed amount of drug. However, coated micro needles also have the problem of remaining after penetration into the skin.

Accordingly, various researches on microneedles capable of improving the supplyability of drugs by overcoming the disadvantages while maintaining the advantages of the molten microneedles and coated microneedles have been continuously carried out in recent years.

Korean Patent Publication No. 2014-0084042 Japanese Patent No. 5495034 Korean Patent Publication No. 2014-0010425

SUMMARY OF THE INVENTION It is an object of the present invention to provide a microneedle capable of allowing a predetermined amount of a drug solution to be placed in an upper end portion of a needle without melting the needle portion of the microneedle,

Another object of the present invention is to provide a micro needle manufacturing method capable of providing a micro needle capable of supplying a fixed amount of a chemical solution.

In order to accomplish the above object, a micro needle according to the present invention comprises a needle portion provided with a water-soluble polymer, a first coating portion formed of a material having a hydrolysis degree greater than a predetermined value and coated on the surface of the needle portion, And a second coating portion coated with a water soluble active ingredient on at least a part of the surface of the first coating portion.

According to one aspect, an end of the needle portion may be provided with a sharp-pointed tip.

According to one aspect, the first coating portion may be coated on the end region or the entire region of the needle portion with a material having a degree of hydrolysis of 90% or more.

According to one aspect, the first coating part may be coated on the surface of the needle part by dipping in a coating solution containing polyvinyl alcohol (PVA).

According to one aspect, the second coating portion may be coated only on an end region of the needle portion coated with the first coating portion.

A micro needle according to a preferred embodiment of the present invention comprises a needle portion having a sharp tip at an end portion, a protective portion provided on a surface of the needle portion with a material having a hydrolysis value equal to or greater than a preset value, And a drug solution portion coated with a drug solution containing a water soluble active ingredient in an end region of the needle portion.

According to one aspect, the protective portion may be dipped in a coating solution containing polyvinyl alcohol (PVA) having a hydrolysis degree of 95% or more and coated on the tip region or the entire region of the needle portion.

According to one aspect, the drug solution may be formed by a biocompatible substance and an additive.

According to one aspect, the biocompatible material is selected from the group consisting of carboxymethylcellulose (CMC), hyaluronic acid (HA), alginic acid, pectin, carrageenan, chondroitin sulfate Sulfates, sulfates, sulfates, sulfates, sulfates, sulfates, sulfates, sulfates, sulfates, sulfates, sulfates, sulfates, sulfates, sulfates, sulfates, sulfates, sulfates, sulfates, But are not limited to, polyanhydride, polyorthoester, polyetherester, polyesteramide, poly butyric acid, poly valeric acid, polyacrylate polyacrylate, ethylene-vinyl acetate polymer, acrylic substituted cellulose acetate, polyvinyl alcohol (PVA), polyvinyl chloride, polyvinyl Polyvinyl fluoride, polyvinyl chloride, chlorosulphonate polyolefins, polyethylene oxide, polyvinylpyrrolidone (PVP), hydroxypropylmethylcellulose (HPMC), ethyl Cellulose acetate (EC), hydroxypropyl cellulose (HPC), carboxymethyl cellulose, cyclodextrin, maltose, lactose, trehalose, cellobiose, iso And may include at least any one of isomaltose, turanose, and lactulose, or may include at least one of a copolymer of monomers forming such a polymer and cellulose.

According to one aspect, the additive is selected from the group consisting of trehalose, oligosaccharide, sucrose, maltose, lactose, cellobiose, hyaluronic acid ( hyaluronic acid, alginic acid, pectin, carrageenan, chondroitin sulfate, dextran sulfate, chitosan, polylysine, collagen, Gelatin, carboxymethyl chitin, fibrin, agarose, polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polymethacrylate, hydroxypropyl methylcellulose (HPMC) But are not limited to, ethylcellulose (EC), hydroxypropylcellulose (HPC), carboxymethyl cellulose, cyclodextrin, gentiobiose, alkyltrimethylammonium bromide (Cetrimide) Such as hexadecyltrimethylammonium bromide (CTAB), Gentian violet, benzethonium chloride, docusate sodium salt, SPAN-type surfactant, at least one of polysorbate (Tween), sodium dodecyl sulfate (SDS), benzalkonium chloride, and glyceryl oleate.

According to one aspect, the active ingredient is selected from the group consisting of? -Interferon,? -Interferon for multiple sclerosis, erythropoietin, polytropine ?, polytropine ?, G-CSF, GM-CSF, human chorionic gonadotropin, Wherein the composition comprises at least one of leutinizing hormone, salmon calcitonin, glucagon, GNRH antagonist, insulin, human growth hormone, peplgastine, heparin, low molecular weight heparin and somatropin, or a Japanese encephalitis vaccine, rotavirus vaccine, influenza vaccine , Polio vaccine, chickenpox vaccine, Alzheimer's disease vaccine, arteriosclerosis vaccine, cancer vaccine, nicotine vaccine, diphtheria vaccine, cervical cancer vaccine, meningococcal vaccine, tetanus vaccine, pertussis vaccine, Lyme vaccine, rabies vaccine, pneumococcal vaccine, Vaccine, cholera vaccine, bupivacaine vaccine, tuberculosis vaccine, rubella vaccine, measles vaccine, mumps vaccine, botulism vaccine, herpes bar Hepatitis B vaccine, Hyaluronic acid, Coenzyme q10, Chitosan, Botox, vitamins and vitamin derivatives, Hydroxy acid, tetracycline (Tetracycline), oxytetracycline, doxycycline, minocycline, benzocaine, Mepivacaine, Lidocaine, Prilocaine, bupivacaine Bupivacaine, Etidocaine, Articaine, Procaine, Propoxycaine, Tetracaine, Ropivacaine, Butacaine, Piperocaine, A vaccine comprising at least one of Piperocaine, Cocaine, Chloroprocaine, Proparacaine and Dyclonine may be included.

A method of manufacturing a micro needle according to a preferred embodiment of the present invention includes the steps of providing a needle portion having a sharp tip at an end thereof with a water-soluble polymer, providing a protective portion on the surface of the needle portion, And a step of providing a drug solution with a drug solution containing a water-soluble active ingredient at an end of the needle portion, wherein the protective portion is formed of a material having a hydrolysis degree equal to or greater than a predetermined value.

According to one aspect of the present invention, in the step of preparing the protective part, the needle part is dipped in a coating solution containing polyvinyl alcohol (PVA) having a hydrolysis degree of 90% or more to protect the surface of the needle part .

According to one aspect, the protector may be coated on the tip area or the entire area of the needle part.

According to one aspect, the drug solution may be formed by a biocompatible material and an additive.

According to one aspect, the biocompatible material is selected from the group consisting of carboxymethylcellulose (CMC), hyaluronic acid (HA), alginic acid, pectin, carrageenan, chondroitin sulfate Sulfates, sulfates, sulfates, sulfates, sulfates, sulfates, sulfates, sulfates, sulfates, sulfates, sulfates, sulfates, sulfates, sulfates, sulfates, sulfates, sulfates, sulfates, But are not limited to, polyanhydride, polyorthoester, polyetherester, polyesteramide, poly butyric acid, poly valeric acid, polyacrylate polyacrylate, ethylene-vinyl acetate polymer, acrylic substituted cellulose acetate, polyvinyl alcohol (PVA), polyvinyl chloride, polyvinyl Polyvinyl fluoride, polyvinyl chloride, chlorosulphonate polyolefins, polyethylene oxide, polyvinylpyrrolidone (PVP), hydroxypropylmethylcellulose (HPMC), ethyl Cellulose acetate (EC), hydroxypropyl cellulose (HPC), carboxymethyl cellulose, cyclodextrin, maltose, lactose, trehalose, cellobiose, iso And may include at least any one of isomaltose, turanose, and lactulose, or may include at least one of a copolymer of monomers forming such a polymer and cellulose.

According to one aspect, the additive is selected from the group consisting of trehalose, oligosaccharide, sucrose, maltose, lactose, cellobiose, hyaluronic acid ( hyaluronic acid, alginic acid, pectin, carrageenan, chondroitin sulfate, dextran sulfate, chitosan, polylysine, collagen, Gelatin, carboxymethyl chitin, fibrin, agarose, polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polymethacrylate, hydroxypropyl methylcellulose (HPMC) But are not limited to, ethylcellulose (EC), hydroxypropylcellulose (HPC), carboxymethyl cellulose, cyclodextrin, gentiobiose, alkyltrimethylammonium bromide (Cetrimide) Such as hexadecyltrimethylammonium bromide (CTAB), Gentian violet, benzethonium chloride, docusate sodium salt, SPAN-type surfactant, at least one of polysorbate (Tween), sodium dodecyl sulfate (SDS), benzalkonium chloride, and glyceryl oleate.

According to one aspect, the active ingredient is selected from the group consisting of? -Interferon,? -Interferon for multiple sclerosis, erythropoietin, polytropine ?, polytropine ?, G-CSF, GM-CSF, human chorionic gonadotropin, Wherein the composition comprises at least one of leutinizing hormone, salmon calcitonin, glucagon, GNRH antagonist, insulin, human growth hormone, peplgastine, heparin, low molecular weight heparin and somatropin, or a Japanese encephalitis vaccine, rotavirus vaccine, influenza vaccine , Polio vaccine, chickenpox vaccine, Alzheimer's disease vaccine, arteriosclerosis vaccine, cancer vaccine, nicotine vaccine, diphtheria vaccine, cervical cancer vaccine, meningococcal vaccine, tetanus vaccine, pertussis vaccine, Lyme vaccine, rabies vaccine, pneumococcal vaccine, Vaccine, cholera vaccine, bupivacaine vaccine, tuberculosis vaccine, rubella vaccine, measles vaccine, mumps vaccine, botulism vaccine, herpes bar Hepatitis B vaccine, Hyaluronic acid, Coenzyme q10, Chitosan, Botox, vitamins and vitamin derivatives, Hydroxy acid, tetracycline (Tetracycline), oxytetracycline, doxycycline, minocycline, benzocaine, Mepivacaine, Lidocaine, Prilocaine, bupivacaine Bupivacaine, Etidocaine, Articaine, Procaine, Propoxycaine, Tetracaine, Ropivacaine, Butacaine, Piperocaine, A vaccine comprising at least one of Piperocaine, Cocaine, Chloroprocaine, Proparacaine and Dyclonine may be included.

According to the present invention having the above-described structure, first, since advantages of the coated microneedle can be added to the molten microneedles, it is possible to provide a microneedle having a fast manufacturing time, no restriction of a transferring material, no change in mechanical strength, It is possible to manufacture favorable micro needles.

Second, since it is made of water-soluble molten material, there is no risk of secondary contamination by needle after application of micro needle.

1 is a cross-sectional view schematically showing a microneedle according to a preferred embodiment of the present invention.
2 is a cross-sectional view schematically showing a modified example of the microneedles shown in Fig.
FIG. 3A is a cross-sectional view of the microneedle shown in FIG. 1, and schematically shows an image obtained by photographing a state where a needle portion is coated up to a protective portion by an optical microscope.
FIG. 3B is a view schematically showing an image obtained by scanning electron microscopy (SEM) of a state in which needle portions are coated to a protective portion in a cross-sectional view of the microneedles shown in FIG.
FIG. 4 is a view schematically showing images taken by an optical microscope of a needle part made of four types of PVA as structural materials.
FIG. 5 is a view schematically showing images taken by an optical microscope, respectively, of a state in which a needle portion made of four kinds of PVA as a structural material is coated with a chemical solution portion containing a dye.
6 is a graph comparing melting times for distilled water and coating solutions according to PVA types.
FIG. 7 is a graph comparing the sharpness of tips of distilled water and coating solution according to the type of PVA.
8 is a graph comparing tip heights for distilled water and coating solution according to PVA type.
FIG. 9 is an image obtained by photographing a change image of the micro needle with an optical microscope when the water-soluble coating solution is exposed according to whether or not the protective portion is coated on the surface of the needle portion.
10 is an image obtained by scanning electron microscope (SEM) images of change images of micro needle at the time of exposure of a water-soluble coating solution according to whether or not a protective portion is coated on the surface of a needle portion.
11 is a flowchart schematically showing a method of manufacturing a micro needle according to a preferred embodiment of the present invention.

Hereinafter, a preferred embodiment of the present invention will be described with reference to the accompanying drawings.

1, the micro needle 1 according to a preferred embodiment of the present invention includes a needle portion 2, a protective portion 3, and a chemical liquid portion 4. [

The needle portion 2 is a needle structure having a sharp tip 2a shape. Although a plurality of such needle portions 2 may be provided and not shown in detail, a plurality of needle portions 2 may be supported by a base (not shown) to be provided in a patch shape. The needle portion 2 is formed of a water-soluble polymer. As a result, the needle portion 2 does not remain and penetrate into the skin due to the material properties, and the hazard is low.

On the other hand, the sharpness of the tip 2a provided at the end of the needle portion 2 is an important factor for determining whether the needle portion 2 is permeable to the skin. That is, when the sharpness degree of the needle portion 2 is reduced, the penetration force for pressing the needle portion 2 toward the skin side for the permeation of the skin is increased. Conversely, if the sharpness of the needle portion 2 is increased, the permeability of the skin can be secured even if the permeation force for pressing the needle portion 2 to the skin is somewhat low.

The protective portion 3 is coated on the surface of the needle portion 2 with a material having a low solubility in water at normal temperature. The protective portion 3 is for protecting the needle portion 2 formed of the water-soluble polymer, that is, the needle structure, by dissolving in the coating process of the chemical solution portion 4 to be described later to prevent the structural deformation, . The protective portion 3 may not remain in the body because the needle portion 2 has a sufficient solubility to be penetrated into the body after the chemical liquid portion 4 is coated and melted by the body fluid in the course of administration for more than a few minutes .

More specifically, the protective portion 3 is provided to protect the entire area of the needle portion 2, as shown in Fig. 1, or to protect the entire area of the needle portion 2 corresponding to the end portion of the needle portion 2 It may be provided to protect only a part of the area. The protective portion 3 is coated on the surface of the needle portion 2 with a polymeric material having a hydrolysis degree of 90% or more and a solubility lower than that of water at room temperature.

In this embodiment, the protective portion 3 is dipped into a coating solution containing polyvinyl alcohol (PVA) having a hydrolysis degree of 95% or more (hereinafter referred to as PVA) to form a needle portion 2 ) Are coated on the surface. For reference, the coating time in which the protective portion 3 is dipped and coated in the coating solution containing PVA takes about 1 second to 5 seconds, and the content of water in the coating solution is about 90% to 95%.

3A and 3B show images taken by an optical microscope and a scanning electron microscope (SEM) of a state in which the protective portion 3 is coated on the needle portion 2 in the sectional view of the micro needle 1, respectively.

The chemical liquid part 4 is coated with a chemical solution containing an aqueous soluble active ingredient in the end region of the needle part 2 with the protective part 3 interposed therebetween. At this time, the chemical liquid part 4 is coated on the tip 2a of the needle part 2 whose surface is protected by the protective part 3, so that deformation of the tip 2a during the chemical liquid coating process is suppressed. The water soluble active ingredient of the chemical liquid part 4 penetrates into the skin and melts, so that the chemical liquid is delivered into the skin.

Table 1 shows the results of experiments using various kinds of PVA according to molecular weight, hydrolysis and viscosity for selecting the material of the protective part 3. In Table 1, And has the following PVA 1 to 4 conditions.

PVA 1: molecular weight 30,000-70,000 [Da] and a degree of hydrolysis 87-90%

PVA 2: molecular weight 146,000-186,000 [Da] and a degree of hydrolysis 87-89%

PVA 3: molecular weight 31,000-50,000 [Da] and a degree of hydrolysis 98-98.8%

PVA 4: molecular weight 146,000-186,000 [Da] and a degree of hydrolysis 99.3-100%

Molecular Weight [ Da ] Hydrolysis [ % ] Viscosity (4%, DW)
[ cps ] PVA 1 30,000-70,000 87.0-90.0 5.2-6.2 PVA 2 146,000-186,000 87.0-89.0 45.0-55.0 PVA 3 31,000-50,000 98.0-98.8 5.5-6.6 PVA 4 146,000-186,000 99.3-100 62.0-72.0

In Table 1, all of PVA 1 to 4 were dissolved in distilled water in a boiling water bath and cooled at room temperature to prepare a PVA solution for making the micro needle 1. At this time, each concentration is 10% (w / w). The PVA solution was poured into a mold, treated for about 1 hour in a centrifuge, and then dried at room temperature. The dried sample was removed from the mold and stored at room temperature to prepare a needle portion (2).

FIG. 4 shows images taken by an optical microscope of the needle portion 2 produced on the basis of the four types of PVA shown in Table 1, and FIG. 5 shows images obtained by using the four kinds of PVA shown in Table 1 An image obtained by photographing a state in which the needle portion 2, which is a needle structure, is coated with the chemical solution portion 4 containing a dye is shown.

4, the composition of the PVA for producing the needle part 2 coated with the protective part 3 is 10% (w / w), and the composition of the chemical solution part 4 coated on the needle part 2 in Fig. W / w of carboxymethylcellulose (CMC), 1% w / w of Tween 80, 5% w / w of Trypan blue, 86% of deionized water, / w, and the viscosity is 4000-5000 cps. The coating of the chemical liquid part 4 was conducted for about 3 seconds and the dipping speed was 1 mm / s. The needle portion 2 coated with the chemical liquid portion 4 was dried under normal temperature-atmospheric pressure conditions, and an image obtained by observing the dried sample through an optical microscope is shown in Fig. For reference, the total length of the micro needle 1 photographed in Figs. 4 and 5 is 600 mu m.

Four kinds of PVA were made with needle parts (2) and coated with a water - soluble coating solution (no protective layer in this case), and then observed through an optical microscope.

The composition of the coating solution used was,

Conditions A) Carboxymethylcellulose (CMC) 10% w / w, Tween 80 1% w / w and Deionized water 89% w / w, viscosity 3807 cps,

Condition B) Carboxymethylcellulose (CMC) 8% w / w, Tween 80 0.8% w / w and Deionized water 91.2% w / w, viscosity 1246 cps,

Condition C) Carboxymethylcellulose (CMC) 4% w / w, Tween 80 0.4% w / w and Deionized water 95.6% w / w and viscosity is 48 cps.

The coating time of the coating solution was 3 seconds, and the dipping speed was 1 mm / s. The dried sample was observed through an optical microscope to measure the degree of transformation.

Referring to FIG. 6, there is shown a graph comparing the dissolution rates for distilled water depending on the type of PVA. After the micro needle 1 was dipped in distilled water at room temperature for 3 seconds, the image of the micro needle 1 was observed through an optical microscope to quantitatively calculate the molten volume. The melting rates of PVA 1 and PVA 2 were 2100 ng / s, 1866.67 ng / s, 900 ng / s and 243.88 ng / s, respectively.

In the case of PVA 1 and PVA 2 having a low degree of hydrolysis, melting of the tip 2a of the needle portion 2 was observed, and PVA 3 and PVA 4 having a high degree of hydrolysis showed that the melting of the needle portion 2 tip 2a Not observed. Therefore, a kind of micro needles 1 made of four kinds of PVA and having a melting rate of less than 1000 ng / s when dipped in distilled water, that is, a kind having a degree of hydrolysis of 95% or more, It can be confirmed that the condition is such that the morphological conversion does not occur by melting.

More specifically, FIG. 6 is a graph comparing melting rates for distilled water (DW) according to PVA types. The graph of FIG. 6 shows the comparison of melting rates after dipping the microneedles according to the PVA type into a coating solution of Carboxymethylcellulose (CMC) 10%, 8% and 4% for 3 seconds.

In the process of dipping the needle portion 2 of the micro needle 1 into the water-soluble coating solution and coating the tip, the conditions under which melting of the tip 2a does not occur depend on the viscosity of the coating solution.

For example, when the coating solution having a viscosity of 4000 cps according to the condition A) is used, the coating time of the PVA micro needle 1 is 0.1 ng / s, and the coating solution having the viscosity of 1000-1500 cps of the condition B) Is 0.5 ng / s. In addition, according to the coating solution having the viscosity of 50-100 cps in the condition C), the melting rate is 0.5 ng / s, and no tip tip deformation is observed under the condition of slow melting.

The PVA species satisfying these conditions in all viscosity regions were PVA with a degree of hydrolysis of more than 95%. In the case of the micro needle 1 made of PVA having a high degree of hydrolysis under the condition, melting of the tip tip is not observed even considering the dipping time (3 seconds) on the surface as well as the total time for drying all the coating solution.

7 is a graph comparing tip sharpness of the tip portion 2a of the needle portion 2 after dipping into the coating solution and distilled water according to the type of PVA. The graph of Fig. 7 shows no tip deformation of the tip 2a that affects the transmittance even under conditions similar to those in Fig. 6, that is, under the following conditions A to D.

Condition A) coating solution having viscosity of 4000 cps based on: Tip sharpness 300 mm ?,

Condition B) Coating solution having viscosity of 1000-1500cps: Tip sharpness 300mm ?,

Condition C) Coating solution having viscosity of 50-100 cps Reference: Tip sharpness 300 mm ?,

Condition D) Distilled water (DW) Standard: Tip sharpness 500mm?

That is, PVA having a degree of hydrolysis of 95% or more was a PVA type satisfying negligible conditions of deformation affecting skin permeability in all viscosity regions. In the case of the micro needle 1 made of PVA having a high degree of hydrolysis under the condition, melting of the tip tip is not observed in consideration of the time (3 seconds) for dipping on the surface and the total time for drying the coating solution .

FIG. 8 is a graph showing a change in tip height variation after dipping into the coating solution and distilled water according to the type of PVA. The amount of tip height variation corresponding to the above-described conditions is as follows.

Condition A) coating solution having viscosity of 4000 cps Reference: tip height variation 10 mm

Condition B) Coating solution having viscosity of 1000-1500 cps Reference: Tip height variation 20 mm,

Condition C) Coating solution having viscosity of 50-100 cps Standard: Tip height variation 20 mm,

Condition D) DW standard: Tip height variation 30mm

For reference, the loss of the tip 2a is not observed under the condition D). That is, PVA having a degree of hydrolysis of 95% or more is suitable as a PVA species satisfying these conditions in all the viscosity regions.

Therefore, it can be confirmed that PVA having a low solubility at room temperature and a degree of hydrolysis of 95% or more is most suitable as a material for the protective part 3 including PVA coated on the surface of the needle part 2. Hyaluronic acid (HA), carboxymethylcellulose (CMC), PVA polymer surface with low degree of hydrolysis (PVA) polymer surface (PVA) having a degree of hydrolysis of more than 95% In a dip coating manner. The dipping speed at this time was 5 mm / s.

An image obtained by comparing the micro-needle 1 thus manufactured with an optical microscope and a scanning electron microscope (SEM) compared with conventional micro needles without the protective portion 3 is shown in FIGS. 9 and 10. FIG. The composition of the coating solution used was Carboxymethylcellulose (CMC) 8% w / w, deionized water 92% w / w, viscosity 1246 cps, coating lasted for 1 second, At a rate of 1 mm / s, and dried at room temperature to atmospheric pressure.

9 and 10, it can be confirmed that the shape distortion of the tip 2a is the lowest in the case of the micro needle 1 provided with the protective portion 3 provided by coating the needle portion 2 with PVA.

A manufacturing method of the microneedle 1 according to the present invention having the above-described structure will be described with reference to FIG.

11, the method of manufacturing the micro needle 1 includes the step of providing the needle part 2, the step of providing the protective part 3, and the step of providing the chemical part 4 .

The step (10) of preparing the needle part (2) is provided with the needle part (2) having a tip (2a) at the end. At this time, the needle portion 2 is made of a water-soluble polymer. In this embodiment, the needle portion 2 can be manufactured by a molding method in which a water-soluble polymer is supplied to a mold (not shown) having a tip groove corresponding to the shape of the tip 2a. Here, the tip 2a of the needle portion 2 may have a sharp cone or a polygonal pyramid, and is not limited to a quadrangular pyramid as in the present embodiment.

The step of preparing the protective part 3 20 is provided by coating the surface of the needle part 2 with the protective part 3. The protective portion 3 is dipped in a coating solution containing polyvinyl alcohol (PVA) having a low water solubility at room temperature and a degree of hydrolysis of 90% or more, preferably 95% or more, to form a needle portion 2, The protective portion 3 is coated on the surface of the protective layer 3. At this time, the coating area of the protective part 3 may be the entire surface of the needle part 2 as shown in FIG. 1 or only the area corresponding to the tip 2a as shown in FIG.

The chemical solution part 4 preparing step 30 coating the tip 2a of the needle part 2 provided with the protective part 3 with a chemical solution containing a water soluble active ingredient. At this time, the surface of the needle portion 2 is protected by the protective portion 3, so that tip 2a is not deformed during operation in which the chemical solution portion 4 is coated on the needle portion 2. [

On the other hand, the chemical liquid in the chemical liquid part 4 is formed by the biocompatible material and the additive. Herein, the biocompatible material may be selected from the group consisting of carboxymethylcellulose (CMC), hyaluronic acid (HA), alginic acid, pectin, carrageenan, chondroitin sulfate, The present invention relates to a pharmaceutical composition comprising at least one compound selected from the group consisting of dextran sulfate, chitosan, polylysine, carboxymethyl chitin, fibrin, agarose, pullulan, polyanhydride Polyorthoesters, polyether esters, polyester amides, poly butyric acids, poly valeric acids, polyacrylates, and the like. , Ethylene-vinyl acetate polymers, acrylic substituted cellulose acetates, polyvinyl alcohols (PVA), polyvinyl chloride, polyvinyl fluoride (polyvinyl fluoride), polyvinyl imidazole (polyvinyl), chlorosulphonate polyolefins, polyethylene oxide, polyvinylpyrrolidone (PVP), hydroxypropylmethylcellulose (HPMC), ethylcellulose EC), hydroxypropylcellulose (HPC), carboxymethyl cellulose, cyclodextrin, maltose, lactose, trehalose, cellobiose, isomaltose At least one of isomaltose, turanose and lactulose, or a copolymer of monomers forming such a polymer and cellulose.

The additive may be selected from the group consisting of trehalose, oligosaccharide, sucrose, maltose, lactose, cellobiose, hyaluronic acid, But are not limited to, alginic acid, pectin, carrageenan, chondroitin sulfate, dextran sulfate, chitosan, polylysine, collagen, gelatin, carboxymethyl (EC), carboxymethyl chitin, fibrin, agarose, polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polymethacrylate, hydroxypropylmethylcellulose (HPMC), ethylcellulose ), Hydroxypropylcellulose (HPC), carboxymethyl cellulose, cyclodextrin, gentiobiose, alkyltrimethylammonium bromide (Cetrimide), hexadecyltrimethoxysilane methylammonium bromide (CTAB), Gentian violet, benzethonium chloride, docusate sodium salt, SPAN-type surfactant, polysorbate (Tween), sodium dodecyl sulfate (SDS), benzalkonium chloride, and glyceryl oleate.

In addition, the active ingredient may be selected from the group consisting of α-interferon, β-interferon for multiple sclerosis, erythropoietin, polytropine β, polytrophin α, G-CSF, GM- CSF, human chorionic gonadotropin, leutinizing Or at least one of heparin, low molecular weight heparin, and somatropin, or a Japanese encephalitis vaccine, a rotavirus vaccine, an influenza vaccine, a polio vaccine , Varicella vaccine, Alzheimer's disease vaccine, atherosclerotic vaccine, cancer vaccine, nicotine vaccine, diphtheria vaccine, cervical cancer vaccine, meningococcal vaccine, tetanus vaccine, pertussis vaccine, Lyme vaccine, rabies vaccine, pneumococcal vaccine, yellow fever vaccine, Vaccine, bupivacaine, tuberculosis vaccine, rubella vaccine, measles vaccine, mumps vaccine, botulism vaccine, herpes virus vaccine, Hyaluronic acid, Coenzyme q10, Chitosan, Botox, vitamins and vitamin derivatives, Hydroxy acid, Tetracycline, and the like, as well as other DNA vaccines, hepatitis B vaccines, hyaluronic acid, Oxytetracycline, doxycycline, minocycline, benzocaine, mepivacaine, lidocaine, prilocaine, bupivacaine, But are not limited to, Etidocaine, Articaine, Procaine, Propoxycaine, Tetracaine, Ropivacaine, Butacaine, Piperocaine, ), Cocaine, chloroprocaine, proparacaine, and dyclonine. The term " vaccine "

As described above, the micro needle 1 finally prepared up to the chemical liquid part 4 is finally dried by drying at room temperature. The micro needle 1 can suppress the deformation of the tip 2a of the needle portion 2 during the coating process of the chemical liquid portion 4 by the protective portion 3 and is excellent in resistance to moisture in air during storage Do. Further, as the micro needles 1 are all made of water-soluble materials, they are not penetrated into the skin and then melted and remain.

Although the present invention has been described with reference to the preferred embodiments thereof, it will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit and scope of the invention as defined in the following claims. It can be understood that

1: Micro needle 2: Needle part
2a: tip 3, 3 ?: protection unit
4: chemical liquid part

Claims (18)

A needle portion provided with a water-soluble polymer;
(PVA) having a hydrolysis ratio of 95% or more and 100% or less and a solubility in water at room temperature lower than that of the needle portion, wherein the first portion coated with the first portion coated on the surface of the needle portion Coating portion; And
A second coating portion in which a water soluble active ingredient is coated on at least a part of the surface of the first coated portion;
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Wherein the first coating portion protects the needle portion from being dissolved during the coating process of the second coating portion.
The method according to claim 1,
And the end of the needle portion is provided with a sharp-pointed tip.
The method according to claim 1,
Wherein the first coating portion is coated on an end region or an entire region of the needle portion.
The method of claim 3,
Wherein the first coating portion is coated on a surface of the needle portion by dipping in a coating solution containing polyvinyl alcohol (PVA).
The method according to claim 1,
Wherein the second coating portion is coated only on an end region of the needle portion coated with the first coating portion.
A needle portion having a pointed tip at its end;
A protecting part provided on the surface of the needle part with a polymeric material having a hydrolysis degree of 95% or more and 100% or less; And
A drug solution portion coated with a drug solution containing an active water soluble component at an end region of the needle portion with the protective portion interposed therebetween;
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Wherein the polymer material of the protector includes polyvinyl alcohol (PVA) having a lower solubility in water at room temperature than the needle portion so that the needle portion is not dissolved during the coating process of the chemical liquid portion.
The method according to claim 6,
Wherein the protective portion is dipped in a coating solution containing the polyvinyl alcohol (PVA) to be coated on the tip area or the entire area of the needle part.
The method according to claim 6,
Wherein the drug solution is formed by a biocompatible material and an additive.
9. The method of claim 8,
The biocompatible material may be,
Carboxymethylcellulose (CMC), hyaluronic acid (HA), alginic acid, pectin, carrageenan, chondroitin sulfate, dextran sulfate, Chitosan, polylysine, carboxymethyl chitin, fibrin, agarose, pullulan, polyanhydride, polyorthoesters (for example, polyorthoesters, polyetheresters, polyesteramides, polybutyric acids, polyvaleric acids, polyacrylates, ethylene-vinyl acetate, and the like. -vinyl acetate polymer, an acrylic substituted cellulose acetate, a polyvinyl alcohol (PVA), a polyvinyl chloride, a polyvinyl fluoride, Polyvinyl chloride, chlorosulphonate polyolefins, polyethylene oxide, polyvinylpyrrolidone (PVP), hydroxypropylmethylcellulose (HPMC), ethylcellulose (EC), hydroxypropylcellulose ( HPC, carboxymethyl cellulose, Cyclodextrin, Maltose, Lactose, Trehalose, Cellobiose, Isomaltose, Turanose, And lactulose, or a micro-needle comprising at least one of a copolymer of monomers and cellulose which form such a polymer.
9. The method of claim 8,
Preferably,
But are not limited to, trehalose, oligosaccharide, sucrose, maltose, lactose, cellobiose, hyaluronic acid, alginic acid ( alginic acid, pectin, carrageenan, chondroitin sulfate, dextran sulfate, chitosan, polylysine, collagen, gelatin, carboxymethyl chitin ), Fibrin, agarose, polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polymethacrylate, hydroxypropylmethylcellulose (HPMC), ethylcellulose (EC) But are not limited to, cellulose derivatives such as propylcellulose (HPC), carboxymethyl cellulose, cyclodextrin, gentiobiose, alkyltrimethylammonium bromide (Cetrimide), hexadecyltrimethylammonium bromide e. g. CTAB), Gentian Violet, benzethonium chloride, docusate sodium salt, SPAN-type surfactant, polysorbate Wherein the micro needle comprises at least one of sodium hypochlorite, sodium dodecyl sulfate (SDS), benzalkonium chloride, and glyceryl oleate.
The method according to claim 6,
The above-
alpha-interferon, beta-interferon for multiple sclerosis, erythropoietin, polytropin beta, polytrophin alpha, G-CSF, GM-CSF, human chorionic gonadotropin, leutinizing hormone, salmon calcitonin, Glucagon, GNRH antagonist, insulin, human growth hormone, peplgastine, heparin, low molecular weight heparin, and somatropin,
A vaccine for the treatment of cancer of the uterine cervix, a vaccine for cervical cancer, a vaccine for cervical cancer, a vaccine for tetanus, a vaccine for pertussis, a vaccine for pertussis, Lyme disease Vaccine against rubella, vaccine against rabies, pneumococcal vaccine, yellow fever vaccine, cholera vaccine, bovine spongiform encephalopathy, tuberculosis vaccine, rubella vaccine, measles vaccine, mumps vaccine, botulism vaccine, herpes virus vaccine, (Hyaluronic acid), coenzyme q10, chitosan, botox, vitamins and vitamin derivatives, hydroxy acid, tetracycline, oxytetracycline, doxycycline ), Minocycline, benzocaine, Mepivacaine, Lidocaine, Prilocin, arose, bupivacaine, etidocaine, articaine, procaine, propoxycaine, tetracaine, ropivacaine, A vaccine comprising vaccines comprising at least one of Butacaine, Piperocaine, Cocaine, Chloroprocaine, Proparacaine and Dyclonine, You guys.
Providing a needle portion having a pointed tip at an end thereof with a water-soluble polymer;
Providing a protective portion on the surface of the needle portion; And
Providing a chemical liquid part with a chemical solution containing an aqueous soluble active ingredient at an end of the needle part with the protective part interposed therebetween;
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Wherein the protective portion is formed of a polymer material containing polyvinyl alcohol (PVA) having a hydrolysis degree of 95% or more and 100% or less and a solubility in water at room temperature lower than that of the needle portion, Wherein the micro-needle is protected from being dissolved during the preparation process.
13. The method of claim 12,
The protecting unit may include:
Wherein the needle portion is dipped in a coating solution containing polyvinyl alcohol (PVA) to coat the protective portion on the surface of the needle portion.
14. The method of claim 13,
Wherein the protector is coated on the tip region or the entire region of the needle portion.
13. The method of claim 12,
Wherein the chemical liquid is formed by a biocompatible material and an additive.
16. The method of claim 15,
The biocompatible material may be,
Carboxymethylcellulose (CMC), hyaluronic acid (HA), alginic acid, pectin, carrageenan, chondroitin sulfate, dextran sulfate, Chitosan, polylysine, carboxymethyl chitin, fibrin, agarose, pullulan, polyanhydride, polyorthoesters (for example, polyorthoesters, polyetheresters, polyesteramides, polybutyric acids, polyvaleric acids, polyacrylates, ethylene-vinyl acetate, and the like. -vinyl acetate polymer, an acrylic substituted cellulose acetate, a polyvinyl alcohol (PVA), a polyvinyl chloride, a polyvinyl fluoride, Polyvinyl chloride, chlorosulphonate polyolefins, polyethylene oxide, polyvinylpyrrolidone (PVP), hydroxypropylmethylcellulose (HPMC), ethylcellulose (EC), hydroxypropylcellulose ( HPC, carboxymethyl cellulose, Cyclodextrin, Maltose, Lactose, Trehalose, Cellobiose, Isomaltose, Turanose, And lactulose, or a copolymer of monomers forming such a polymer and cellulose. ≪ Desc / Clms Page number 20 >
16. The method of claim 15,
Preferably,
But are not limited to, trehalose, oligosaccharide, sucrose, maltose, lactose, cellobiose, hyaluronic acid, alginic acid ( alginic acid, pectin, carrageenan, chondroitin sulfate, dextran sulfate, chitosan, polylysine, collagen, gelatin, carboxymethyl chitin ), Fibrin, agarose, polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polymethacrylate, hydroxypropylmethylcellulose (HPMC), ethylcellulose (EC) But are not limited to, cellulose derivatives such as propylcellulose (HPC), carboxymethyl cellulose, cyclodextrin, gentiobiose, alkyltrimethylammonium bromide (Cetrimide), hexadecyltrimethylammonium bromide e. g. CTAB), Gentian Violet, benzethonium chloride, docusate sodium salt, SPAN-type surfactant, polysorbate Wherein the microspheres comprise at least one selected from the group consisting of sodium dodecyl sulfate (SDS), benzalkonium chloride, and glyceryl oleate.
13. The method of claim 12,
The above-
alpha-interferon, beta-interferon for multiple sclerosis, erythropoietin, polytropin beta, polytrophin alpha, G-CSF, GM-CSF, human chorionic gonadotropin, leutinizing hormone, salmon calcitonin, Glucagon, GNRH antagonist, insulin, human growth hormone, peplgastine, heparin, low molecular weight heparin, and somatropin,
A vaccine for the treatment of cancer of the uterine cervix, a vaccine for cervical cancer, a vaccine for cervical cancer, a vaccine for tetanus, a vaccine for pertussis, a vaccine for pertussis, Lyme disease Vaccine against rubella, vaccine against rabies, pneumococcal vaccine, yellow fever vaccine, cholera vaccine, bovine spongiform encephalopathy, tuberculosis vaccine, rubella vaccine, measles vaccine, mumps vaccine, botulism vaccine, herpes virus vaccine, (Hyaluronic acid), coenzyme q10, chitosan, botox, vitamins and vitamin derivatives, hydroxy acid, tetracycline, oxytetracycline, doxycycline ), Minocycline, benzocaine, Mepivacaine, Lidocaine, Prilocin, arose, bupivacaine, etidocaine, articaine, procaine, propoxycaine, tetracaine, ropivacaine, A vaccine comprising vaccines comprising at least one of Butacaine, Piperocaine, Cocaine, Chloroprocaine, Proparacaine and Dyclonine, Needle manufacturing method.

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