KR20150144118A - Microneedle coated by oriental medicine compositions and method for manufacturing thereof - Google Patents

Abstract

The present invention relates to a microneedle coated with an oriental medicine composition and a manufacturing method thereof, having an oriental mixture coated on the surface of a microneedle, which comprises: an oriental medicine composition containing Bupleurum falcatum L., dried orange peel, Angelica gigas Nakai, Atractylodes japonica, Valerianae radix, Glycyrrhiza uralensis Fischer, Puerariae radix, Poria cocos, Mentha arvensis, Gardenia jasminoides Ell, musk, and extract powder of chicken sternal cartilage; a water-soluble natural polymer; a natural viscosity increasing agent; and sterilized and distilled water. The composition has excellent anti-aging effects and anti-arthritic effects, by gradually dissolving an oriental medicine mixture by moisture contained in the skin when the microneedle is attached on a treatment region, forming a channel on skin peel and an inner skin layer, and transmitting an active ingredient of the oriental medicine composition to the inside of the percutaneous skin in a rapid and effective manner.

Description

Technical Field [0001] The present invention relates to a microneedle coated with a herbal composition and a method for manufacturing the same,

The present invention relates to a microspheres coated with a herbal composition and a method for producing the microspheres. When the microspheres coated with the herbal composition are adhered to the treatment site, the herbal mixture is slowly dissolved by the moisture contained in the skin, great.

Conventional methods for delivering an effective ingredient through the skin are mainly using a needle using a standard syringe or a catheter. This method not only causes fears and pain on the needles and local damage to the skin, And is not ideal for slowly delivering efficacy.

The conventional transdermal patches are classified into three types: matrix type, storage layer type, and adhesive type. The conventional transdermal patches using the transdermal absorption method are classified into three types: In the middle matrix type, the active ingredients are dispersed in the matrix layer of the polymer or the pressure-sensitive adhesive to control the release of the drug. The storage layer type is a form in which the active ingredients are contained in a certain film or film to control and adhere to release. And non-soluble structures (such as plastics), such as plastics, with thin coatings. The major disadvantages of these are low absorption rate of drug through skin, limited concentration and quantification of active ingredients, low skin permeability to skin stratum corneum, and easy exposure to external contamination and various physical damage.

Meanwhile, as a conventional technique for delivering through the skin, methods for delivering the active ingredients using iontophoresis, electroporation, and ultrasound using chemical phenomena are used, but a separate device It is inconvenient to use, untrained is difficult to manipulate, has a problem in skin safety, and has impractical disadvantages.

In addition, as another delivery technique through the skin, there is a needle used in Oriental medicine.

The acupuncture used in Oriental medicine is largely divided into traditional oriental medicine and medicinal medicine. In general, the one-sided needle is composed of a needle-like needle for penetrating the skin at the upper part of the stomach, and a needle-shaped body which is formed thickly at the other end of the stomach and the stomach.

The principle of medicine is to stimulate the important acupuncture points and meridians with acupuncture, and to inject acupuncture ingredients of herbal medicine into acupuncture points, thereby simultaneously treating the acupuncture itself and the treatment effect by injection of a specific drug. However, in the case of existing medicines, it is a primitive procedure using syringe needles and syringes, which causes pain and trauma during penetration through the skin, which gives a rejection feeling and is incompatible with the one-shot dispenser.

Thus, there is a continuing need for external stimuli that penetrate the skin without pain, such as one-sided acupuncture, and acupuncture that maximizes internal therapy that delivers the drug.

Korea Patent No. 0806026 Korean Patent No. 0656244

An object of the present invention is to provide a microspheres coated with a herbal composition having a herbicide-coated microspheres adhering to a treatment site, wherein the herbal mixture is slowly dissolved by the moisture contained in the skin, thereby exerting an effect on aging and arthritis.

It is another object of the present invention to provide a method for producing a microspheres coated with the herbal composition.

In order to accomplish the above object, the microspheres coated with the herbal composition of the present invention include heat-treated microcapsules containing chrysoprase, dermis, Angelica keiskei keishi, gill root, licorice root, Herbal composition; Water soluble natural polymers; Natural thickener; And sterile distilled water may be coated on the microneedle surface.

The herbal mixture may contain 1 to 100 parts by weight of the water-soluble natural polymer, 3 to 100 parts by weight of the natural thickening agent, and 100 to 700 parts by weight of sterilized distilled water, based on 100 parts by weight of the herbal composition.

The herbal composition may contain 1 to 10% by weight of Seal, 1 to 15% by weight of dandelion, 5 to 20% by weight of Angelica keiskei, 5 to 20% by weight of Creation date, 1 to 10% 20 to 20% by weight of bamboo shoots, 5 to 20% by weight of bamboo shoots, 1 to 10% by weight of peppermint, 1 to 10% by weight of gardenia, 0.01 to 2% by weight of musk, and 5 to 40% by weight of chick chest cartilage extract powder.

The microspheres coated with the herbal composition can inhibit hyaluronidase activity.

The herbal mixture may be coated to a thickness of 0.01 to 0.5 mm.

A plurality of grooves may be formed in the microspheres.

The water-soluble natural polymer may be at least one selected from the group consisting of corn starch powder, sweet potato starch powder and rice flour.

The natural thickening agent may be at least one selected from the group consisting of oligosaccharides, fructose, maltose, honey, and agar.

The microspheres may be titanium, titanium alloys or apatite ceramics.

According to another aspect of the present invention, there is provided a method of manufacturing a microspheres coated with a herbal composition comprising the steps of: (a) grinding a seed meal, a dermis, a ginseng root, a ginseng root, a ginseng root, a licorice root, step; (b) preparing a herbal composition by adding musk and chest chest cartilage extract powder to the pulverized powder; (c) mixing the herbal composition, the water-soluble natural polymer, the natural thickener, and the sterilized distilled water to prepare a herbal mixture; (d) placing the herbal mixture in a mold, leaving the mixture under a vacuum pressure of -400 to -600 mmHg, and inserting a microspheres into a mold into which the herbal mixture is introduced; And (e) drying the micro-needle-inserted mold at a temperature of 20 to 60 ° C at a relative humidity of 20% or less to coat the micro-needle surface with the herbal mixture.

Between the step (b) and the step (b), the herbal composition and the sterilized distilled water are mixed at a weight ratio of 1: 2 to 5, and the mixture is maintained at a temperature selected from 100 to 120 ° C, A step of reducing 90% and then filtering it may be added.

The microspheres coated with the herbal composition of the present invention can simultaneously perform surgical excitation of the herbal medicine and medicinal drug delivery of the herbal medicine. Specifically, when the microspheres are adhered to the treatment site, the herbal mixture is slowly dissolved by the moisture contained in the skin while stimulating the menstrual blood, thereby forming channels in the skin horny layer and the dermal layer, so that the effective ingredient of the herbal composition can be rapidly and effectively transdermally It is effective for aging and arthritis.

In addition, since the microspheres coated with the herbal composition of the present invention release the active ingredient of the herbal composition for a few days to several days, the therapeutic effect is excellent, there is no need to add a separate preservative component, It is easy. In addition, it can be protected from external environmental factors and maintain stability.

When the microspheres coated with the herbal composition are adhered to the treatment site, the herbal mixture is gradually dissolved by the water contained in the skin, thereby forming channels in the skin horny and dermis layers so that the effective ingredient of the herbal composition is rapidly and effectively transdermally delivered Aging and arthritis, and a method for producing the same.

Hereinafter, the present invention will be described in detail.

The herbal composition coated with the herbal composition of the present invention is a herbal composition comprising a chrysoprase, dermis, Angelica keiskei, crepe, licorice root, licorice root, gypsum, peppermint, gardenia, musk and chicken chest cartilage extract powder; Water soluble natural polymers; Natural thickener; And sterilized distilled water are coated on the surface of the micropipette.

Herbal composition

The herbal composition includes a mixture of chrysoprase, dermis, Angelica keiskei keishi, Gilchougang, licorice root, bamboo shoot, peppermint, gardenia, musk and chest chest cartilage extract powder. The mixed powder is fired by heat treatment. When any one of the herbal medicines contained in the herbal composition is removed, the degree of hyaluronidase activity inhibition is not high and the elasticity, that is, the bone mineral density and the bone bioindex, may be low. The hyaluronic acid is a substance contained in a large amount of cartilage tissue in vivo, plays a major role in increasing the elasticity of the cartilage tissue, has a high moisture content, and has excellent viscoelasticity. In general, accelerated degradation of hyaluronic acid is observed in osteoarthritis patients. There are reports that hyaluronidase and the like increase the cell death of articular cartilage cells and decrease the metabolism of cartilage cells to promote degenerative changes of cartilage tissue. Therefore, inhibiting hyaluronidase, a degrading enzyme of hyaluronic acid, has an effect of treating osteoarthritis.

The significance of the content of each medicinal material described below indicates the significance of the characteristics of medicinal herb after it has been formulated.

Radix Bupleuri (Latin name: Bupleurum falcatum L., Umbelliferae) is the first herbal medicinal substance recorded in the Divine Husbandman's Materia Medica. It has symptoms of repeated cold and fever, chest discomfort, , Headache, dizziness, schizophrenia, withdrawal, menstrual relief, uterine drainage, and hernia. Bupleurumol, oleic acid, linoleic acid, palmitic acid, saikosaponin A, B, C, saikosaponin A, B, C, E, and G (saikogenin F, E, G).

When the content of the citric acid is out of the above range, the skin elasticity is lowered, and the elasticity, that is, the bone mineral density and the bone bioindex, may be low.

The dermis refers to the rinds of citrus unshiu (Citrus unshiu) and its plants belonging to the genus Rutaceae distributed throughout the country, and a large amount of components such as flavonoid and vitamin are known as components thereof. , Dryness, dryness, and so on.

The dermis is contained in an amount of 1 to 15% by weight, preferably 5 to 15% by weight. When the content of the dermis is out of the above range, the skin elasticity is lowered and the hyaluronidase activity inhibition degree may not be high.

The Angelica acutiloba KITAGAWA belonging to the Umbelliferae distributed throughout the country and the roots of the plants belonging to the genus Angelica acutiloba KITAGAWA refer to ligustilide, butylidenephthalide, Components such as Cnidilide, Isocnilide, sesquiterpene and the like are known, and a therapeutic action for dysmenorrhea, abdominal pain and the like are known.

When the content of Angelicae gigantis is out of the above range, the skin elasticity is lowered, the hyaluronidase activity inhibition is not high, and the bone mineral density and the bone bioassay index The elastic force may be low.

The above effect is effective for sweating, diarrhea, analgesic and dryness, and is effective for gastroenteritis and cold. Especially, it plays a role of suppressing and stimulating central nervous excitement and has an excellent effect on obesity. Atractylone, Atractylol and vitamins A and D are the main pharmacological ingredients.

The above-mentioned range is 5 to 20% by weight, preferably 5 to 10% by weight. When the preparation is used within the above range, the coated herbal mixture is not easily decayed and the patient is relieved of the pain, Can be exercised.

The rootstock is a relative plant belonging to the same genus, and is a common herbaceous plant. This medicine has a peculiar smell, and the taste is spicy and the quality is warm. It is used for chest leaks caused by mental anxiety, insomnia, easily frightening symptoms, nervous breakdown, myocarditis, postpartum heart disease, heart failure, altitude sickness, menstrual irregularity, stomach cramps, joint points, bruises. Pharmacological actions such as sedation, antipyretic action, hypotension, Gram-positive bacterial inhibitory action, and diuretic action have been reported.

The long root is contained in an amount of 1 to 10% by weight, preferably 1 to 5% by weight. When the long-root muscle is used in the above-mentioned range, the patient can be relieved by the pain,

The licorice (Glycyrrhiza uralensis FISCH.) Is a perennial herb of soybean. Licorice is harmonized with all the medicines in herbal medicine and not only increases the efficacy, but also alleviates various pain and urgency symptoms by relieving pain medication. It is used for external use, and itself has a weakness such as a neutralizing action of the poison. It contains all of triterpene saponin and glycyrrhizin in roots and rhizomes of plant. It has all the detoxification effects against bacterial toxins as well as drug poisoning, food poisoning, metabolism of body metabolism, And thyroid gland hormone levels.

The licorice content is 1 to 15% by weight, preferably 5 to 15% by weight. When the content of licorice is out of the above range, skin elasticity is lowered, hyaluronidase activity inhibition is not high and bone mineral density and bone- The elastic force may be low.

The pupa is a bark of roots and has no smell, it is soft and sweet and spicy. Changgeun sweat, fever fever, high fever, cure headache and stop the thirst. It is used for digestion, headache, anemia, dysentery, abdominal pain, dryness, cold, vomiting and bleeding of wife. It blooms raw roots and sucks and drinks. The fruit of the 칡 is called the gag, and it is effective in the diarrhea. The 칡 flower which is a 칡 flower has a unique sweetness, and it releases the digestion and strengthens the intestines.

When the content of the granocyte root is out of the above range, the elasticity of the skin may be lowered and the elasticity of bone mineral density and bone bio index may be lowered.

The bacillus has been used in a wide range of diseases such as hypoglycemic effect, prevention of gastric ulcer, dryness, diuretic, sedation, heart palpitations and the like. The components revealed are glucose polysaccharide pachyman and diuretic caloric triterpenone series It contains pachymic acid, polyporenic acid and ergosterol as a steroid. In addition to methyltumulosate, it contains albumin and various other ingredients.

When the content of the berry is out of the above range, the skin elasticity may be lowered and the hyaluronidase activity inhibition may not be high.

The mint is a perennial herbaceous color belonging to the family Lamiaceae. It is effective for symptoms of fever, headache and sweating caused by colds of the ears. It causes redness of eyes, sore throat, tonsillitis, early itchy skin, liver disease, abdominal pain, diarrhea, vomiting , And pharmacological effects such as fever, inflammation, dryness, promotion of bile secretion and suppression of gastric smooth muscle, increased mucus secretion of the respiratory tract, central nervous excitation, and uterine contraction have been reported.

When the content of the peppermint is out of the above range, the skin elasticity may be lowered and the hyaluronidase activity inhibition may not be high.

The Gardeniae Fructus has long been used as a food coloring agent in the gardenia jasmoides Ellis or other relative plants belonging to the Rubiaceae family. In one room, inflammation, diuresis, hemostasis. It is used as antipyretic, sedative, antimicrobial, bile secretion, hepatitis, jaundice, and hematemesis. The pharmacological action of gardenia has been reported to promote the secretion of bile and to protect against the chemical properties of soy sauce.

When the content of the gardenia is out of the above range, the skin elasticity is lowered, the hyaluronidase activity inhibition is not high, and the bone mineral density and the bone bio index The elastic force may be low.

The musk is also musk as a natural animal flavor. Musk deer includes musk, musk, musk, etc. mainly including musk, especially the musk of musk that has less foreign substance and shows excellent efficacy. The main component of musk is a liquid muscone such as colorless oil, and it is used not only as a stimulus for depression, but also as an antidote for paralysis or general paralysis.

 When the content of musk is out of the above range, the elasticity of the skin is lowered, the hyaluronidase activity inhibition is not high, and the bone density and the bone bio index The elastic force may be low.

Chicken Sternum Cartilage (Chicken Sternum Cartilage) is a type of collagen-type two-type structure composed of protein, chondroitin sulfate, moisture, phosphorus, and ash. Collagen is an important protein that constitutes the living body. It is widely distributed in the skin and articular cartilage, and is widely distributed throughout the ligaments, bones, and blood vessels. It is classified into type 1, type 2, type 3 to type 20 according to the distribution and properties in vivo. Among them, the major component of joints is collagen of type 2, except for water. This ingredient acts as a lubricant for the cartilage, and it has been reported that it attracts moisture in the tissue to help soften the movement of joints, thereby alleviating the pain of osteoarthritis and rheumatism, and slowing degeneration of cartilage.

The chick chest cartilage extract powder is contained in an amount of 5 to 40% by weight, preferably 15 to 40% by weight. When the content of chick chest cartilage extract powder is out of the above range, the skin elasticity is poor and the hyaluronidase activity inhibitory effect And the elasticity, ie, bone density and bone bioindex, may be low.

Water-soluble natural polymer

The water-soluble natural polymer is a substance that forms a coating film on the outer surface and coating the herbal mixture in the shape of a mold, and specifically includes at least one selected from the group consisting of corn starch powder, sweet potato starch powder, and rice flour.

The water-soluble natural polymer is used in an amount of 1 to 100 parts by weight, preferably 5 to 20 parts by weight, based on 100 parts by weight of the herbal composition. When the content of the water-soluble natural polymer is less than the above lower limit, the viscosity of the herbal mixture may be difficult to be coated on the micro needle, and when the content of the water-soluble natural polymer is higher than the upper limit, the viscosity of the herbal mixture may be too high, It is difficult to inject and the herbal mixture is difficult to mix uniformly and is not well soluble in water.

natural Incrementer

The natural thickening agent is mixed with the water-soluble natural polymer to make the surface slippery when the herbal mixture is cured and has a preservative function as well as a pH controllability. Specifically, the natural thickening agent is composed of oligosaccharide, fructose, maltose, At least one selected from the group consisting of

The natural thickening agent is 3 to 100 parts by weight, preferably 5 to 20 parts by weight based on 100 parts by weight of the herbal composition. When the content of the natural thickener is less than the lower limit, the drying time for solidifying the herbal mixture is increased more than twice, and the microbial propagation can easily occur. When the content exceeds the upper limit, cracks easily occur in the coating, I can not.

The material of the microspheres coated with the herbal mixture is not particularly limited as long as it is a material harmless to the human body. Preferably, titanium, titanium alloy or apatite ceramics can increase the adhesive strength of the herbal mixture. Also, the microspheres may be conical, tetrahedral or quadrangular with a length of 1 to 5 mm and a head diameter of 5 to 20 mm; Plastics, cotton, rayon, or the like and used as a fine needle (fine needle) of a patch. When the patch is used as a fine needle, a plurality of fine needles protrude from one side of the patch.

The fine needle is provided with a plurality of grooves by a laser or a grinding machine so that a one-way mixture is easily coated and serves as a support to prevent the coating film from falling off, and resistance to invasion of the skin can be reduced.

The herbal mixture forms a coating film on the microspheres to a thickness of 0.01 to 0.5 mm, which has self-leveling characteristics by water-soluble natural polymers and natural thickeners, and is self-coating to a uniform thickness. Therefore, the mold is the same as that used for molding the shape of the coating film.

The present invention also provides a method for producing a microspheres coated with a herbal composition.

The method for preparing microspheres coated with the herbal composition of the present invention comprises the steps of: (a) crushing the callus, the dermis, the ginseng root, the ginseng root, the ginseng root, the licorice root, the ginseng root, the peppermint and the gardenia; (b) preparing a herbal composition by adding musk and chest chest cartilage extract powder to the pulverized powder; (c) mixing the herbal composition, the water-soluble natural polymer, the natural thickener, and the sterilized distilled water to prepare a herbal mixture; (d) placing the herbal mixture in a mold, leaving the mixture under a vacuum pressure of -400 to -600 mmHg, and inserting a microspheres into a mold into which the herbal mixture is introduced; And (e) drying the micro-needle-inserted mold at a temperature of 20 to 60 ° C at a relative humidity of 20% or less to coat the micro-needle surface with the herbal mixture.

In the above steps (a) and (b), crushed pieces of crushed ginger, dandelion, angelica grisea, licorice root, licorice root, To prepare a herbal composition.

If the musk and chest cartilage extract powder are added later, the efficacy of musk and chest cartilage extract powder is further increased, which is preferable for increasing skin elasticity and increasing arthritis effect.

The herbal composition prepared in step (b) may be prepared by mixing the herbal composition and sterilized distilled water at a weight ratio of 1: 2 to 5, and then keeping the temperature constant at a selected temperature of 100 to 120 ° C to reduce the original weight by 30 to 90% Then, it is filtered to form a herbal composition. The filtered herbal composition is made into powder by concentration under reduced pressure and lyophilization.

When a herbal composition containing all the herbal herbicides is added, the skin elasticity and the effect of arthritis can be enhanced. However, when the herbal medicines are separately added and mixed, The effect is poor.

The above formula is a pharmaceutical technology that changes the original properties of herbal medicines by processing the herbal medicines based on the oriental medicine theory. For example, even with the same medicines, coloring materials and sourdoughs may not have the same properties or may differ in their action. These herbal medicines must be processed before use. Such processing is carried out by a stationary plant.

The purpose of the medicinal herb is to: 1. clean and facilitate the storage of medicines, 2. reduce or eliminate the toxicity and side effects of the medicines, 3. make medicines more effective by changing medicines, 4. medicinal effects And 5. To remove the bad smell and taste of herbal medicines and make them better to take.

Next, in the step (c), the herbal composition, the water-soluble natural polymer, the natural thickener and the sterilized distilled water are mixed to prepare a herbal mixture.

Next, in the steps (d) and (e), microspheres are inserted into a mold into which the herbal mixture is injected and dried to prepare a herbal mixture, i.e., a microspheres coated with a herbal composition.

Specifically, the herbal mixture is placed in a grooved mold, and the mold is closed and treated for 5 to 10 minutes under a pressure selected from a vacuum pressure of -400 to -600 mmHg beneath the closed mold, The microcapsules are coated with the herbal mixture to prepare microspheres by inserting the herbal mixture into a mold and drying the microspheres at 20 to 60 캜 at a relative humidity of 20% or less.

It is preferable that the length of the fine needle and the depth of the mold are the same so that the herbal mixture is coated on all surfaces of the fine needle.

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 or scope of the present invention. Such variations and modifications are intended to be within the scope of the appended claims.

Manufacturing Example  1. Preparation of Oriental Compositions

6 weight% of dicalcium phosphate, 5 weight% of dicalcium phosphate, 15 weight% of Angelica grisea, 5 weight% of Ganoderma lucidum, 1.5 weight% of Ganoderma lucidum, 5 weight% of licorice, 10 weight% Were mixed and pulverized. Then, a herbal composition was prepared by adding 0.5% by weight of musk and 30% by weight of chest chest cartilage extract powder.

Preparation Example 2. Preparation of herbal composition

3% by weight of ginger, 3% by weight of ginger, 3% by weight of ginger, 6% by weight of ginger root, 3% by weight of licorice, 17% by weight of ginger root, 17% Were mixed and pulverized. Then, a herbal composition was prepared by adding 0.5% by weight of musk and 12.5% by weight of chest chest cartilage extract powder.

Preparation Example 3. Preparation of Oriental Compositions

The preparation was carried out in the same manner as in Preparation Example 1 except that the musk and chest chest cartilage extract powder were mixed with other medicinal materials at one time and pulverized to prepare a herbal composition.

Preparation Example 4. Preparation of Oriental Compositions

The herbal composition was prepared in the same manner as in Preparation Example 1, but without using the extracts of chopped and chest chest cartilage extracts.

Example 1.

100 parts by weight of the herbal composition prepared in Preparation Example 1 and 250 parts by weight of sterilized distilled water were mixed and heated at 108 DEG C for 6 hours with a fermentation extractor (biofeedback DM-3000, Median, Korea) Then, the mixture was filtered through a filtration apparatus and concentrated under reduced pressure to give 10 parts by weight. The mixture was lyophilized to obtain 6 parts by weight of a powder of the feces herbal composition. 2.5 parts by weight of rice flour as a water-soluble natural polymer, 2.5 parts by weight of sweet potato starch powder, 0.5 part by weight agar agar, 5 parts by weight of honey, 0.5 parts by weight of oligosaccharide and 0.5 parts by weight of maltose; And 100 parts by weight of sterilized distilled water were mixed to prepare a herbal mixture.

After the mold was closed and the mold was closed for 5 minutes while maintaining the vacuum pressure at -500 mmHg under the closed mold, a plurality of pyramidal shaped grooves The microspheres were inserted into a mold filled with the herbal mixture and dried at a relative humidity of 20% or less at 40 캜 for 5 hours to prepare a patch having a microspheres coated with the herbal mixture.

Example 2.

The procedure of Example 1 was repeated except that the herbal composition prepared in Preparation Example 2 was used in place of the herbal composition prepared in Preparation Example 1 to prepare a patch having microspheres coated with a herbal mixture.

Example 3.

A patch having microspheres coated with a herbal mixture was prepared in the same manner as in Example 1 except that the herbal composition prepared in Preparation Example 3 was used in place of the herbal composition prepared in Preparation Example 1.

Comparative Example 1

The preparation was carried out in the same manner as in Example 1 except that the amount of the powder of the fecal herbal composition was increased to 24 parts by weight to prepare a patch having a microspheres coated with a herbal mixture.

Comparative Example 2

Except that the amount of the powder of the fecal herbal composition was increased to 24 parts by weight and the amount of the water-soluble natural polymer was increased to 5 parts by weight of the rice flour and 2.5 parts by weight of the sweet potato starch powder, 0.5 part by weight of agar, 2.5 parts by weight of honey, and 1 part by weight of maltose, thereby preparing a patch having microspheres coated with a herbal mixture.

Comparative Example 3

The procedure of Example 1 was repeated except that the herbal composition prepared in Preparation Example 4 was used in place of the herbal composition prepared in Preparation Example 1 to prepare a patch having microspheres coated with a herbal mixture.

Comparative Example 4

The procedure of Example 1 was repeated except that the herbal composition was not heated at 108 to prepare a patch having microspheres coated with a herbal mixture.

Test Example 1. Measurement of solubility

Fill a 50 ml beaker with 20 ml of purified water and keep the temperature at 24 ° C. The patches prepared in the above Examples and Comparative Examples were fully impregnated with purified water, and the time of completely dissolving in water was measured, and the results are shown in Table 1 below.

division Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Dissolution time
(second) 40 50 55 70 84 50 60

As shown in Table 1 above, it was confirmed that the herbal mixtures of Examples 1 to 3 prepared according to the present invention show fast dissolution time. Among them, Example 1 showed the fastest dissolution time.

On the other hand, Comparative Example 1 in which the content of the herbal mixture is large and Comparative Example 2 in which the amount of the thickening agent is small is likely to have a problem in practical use because of a long dissolving time.

Test Example 2. Measurement of inhibition of hyaluronidase activity

In order to examine the inhibition of hyaluronidase activity of the composition, activity was measured using Morgan-Elson Assay. Hyaluronic acid dissolved in phosphate buffer solution and the extract mixture prepared in the above example dissolved in DMSO were added to each well and cultured at 37 ° C for 20 minutes. After incubation, the compound 48/80 solution was added and secondary cultured. After hyaluronic acid was added and cultured for the third time, K3BO3 was added and the reaction was stopped by heating in hot water. After centrifugation, N-acetylglucosamine, which is produced by degradation of hyaluronidic acid by hyaluronidase, was quantified by colorimetric determination of 585 with DMAB (p-dimethyaminobenzaldehyde) to confirm its activity. Celecoxib (Pfizer) was used as a positive control. The results are shown in Table 2 below.

division Example 1 Example 2 Example 3 Comparative Example 3 Comparative Example 4 Celecoxib Activity inhibition
(%) 61.5 ± 0.48 43.2 ± 0.22 33.3 ± 0.41 21.1 ± 0.29 18.5 ± 0.37 63.2 ± 0.52

As shown in Table 2 above, the herbal composition prepared according to Example 1 of the present invention had a similar inhibition of hyaluronidase activity to celecoxib, which is a positive control, and superior hyaluronidase Activity inhibition.

In particular, it was confirmed that the inhibition degree of hyaluronidase activity in Comparative Example 3 and Comparative Example 4 was extremely low.

Test Example 3. Skin Stability Test

Twenty two subjects (mean age 24.6 years, age range 19 ~ 41 years) were divided into two groups and skin patch tests were performed on the upper bump using Hill Top Chamber. Patients with psoriasis, eczema, other skin lesions, pregnant, lactating or contraceptive, and antihistamines were excluded from the study.

The test sites were wiped with 70% ethanol and dried. Then, the patches prepared in Examples and Comparative Examples were adhered to 20 mm round chambers, respectively, and then fixed on top of the test site. After applying the patch for 24 hours and removing the patch, mark the test area with Marking Pen and observe the test area after 24 hours and 48 hours, respectively. The judgment was made at 24 hours and 48 hours after removal of the patch, and the skin reaction was judged according to the rules of the International Contact Dermatitis Research Group (ICDRG) listed in Table 3 below.

sign Criteria evaluation Mean Score - Negative No stimulation 0 ± Doubtful or slight reaction and erythema Small stimulus 0 to 0.9 + Erythema + Induration Light stimulus 1.0 to 2.9 ++ Erythema + Induration + Vesicle Moderate irritation 3.0 ~ 4.9 +++ Erythema + Induration + Bullae River stimulation 5.0 or higher

Elapsed time Example 1 Example 2 Example 3 Comparative Example 3 Comparative Example 4 24 hours - - - ± ± 48 hours - - - ± +

As shown in Table 4 above, it was confirmed that the herbal mixture prepared according to Examples 1 to 3 of the present invention showed no irritation on the skin of the subject and was a stable substance without skin irritation.

On the other hand, Comparative Examples 3 and 4 showed skin irritation.

Test Example  4. Skin permeability test

The microdish patches of Examples 1 and 2 showing fast dissolution time and excellent hyaluronidase activity inhibition rate in Examples were patches containing 0.5% by weight of musk, and as a indicator substance, normoscon (RT = 23.11) was chromatographed And the retention time (RT) value was confirmed. Then, the skin permeability test was carried out by asking the Clinical Support Center of Samyung University.

The test group was applied to the hair of the hairless mouse and then dissolved in 2 ml of buffer (pH 7.2). As a control, patches having the same composition as in Example 1 but without fine needle were used as a control. The skin permeability (transdermal absorption) of Normuscorn was eluted with Franz diffusion cell at 0, 4, 8, 12 and 24 hours after the elution, and the amount of normuscone was measured by fluorescence This study was performed to compare skin permeability with high performance liquid chromatography (HPLC). Hematoxylin & Eosin staining was used to analyze the permeability of niacinamide.

Franz diffusion cell with a volume of 10 ml and 0.636 ㎠ was used. The experiment was carried out while maintaining circulation at 37 ℃ using a constant temperature water bath and 0.1 mM PBS (pH 7.2) buffer solution was used. In Donor of Franz Cell, the mouse skin, the patch (test group and control), 2 ml of buffer (pH 7.2), and 8 ml of buffer were added to Recptor and the blood flow rate was fixed at 110 rpm. After samples were taken for measurement, immediately same volume of PBS was added to maintain the sink condition.

KH1-hairless mice were adapted for 24 hours at the temperature of 23 ± 3 ℃, humidity of 50 ± 5% and ventilation 10 ~ 15 times / day for 6 weeks at Orient Bio. The skin was extracted with 3.0 × 3.0 ㎝ size and stored at 70 ℃ for use in the experiment.

division Concentration of Normuscone PPM (ug / ml) Example 1 Example 2 Control group 0 hr 0 0 0 4 hr 600 300 0 8 hr 1300 900 40 12 hr 2200 1500 80 24 hr 3700 2700 110

As shown in Table 5, it was confirmed that the herbal mixture prepared according to Examples 1 and 2 of the present invention permeated dozens of times as compared with the control group. This means that the herbal mixture, which can dissolve in the skin when the skin is adhered, effectively permeates the indicator material to the skin, so that other effective ingredients of the herbal medicine are also penetrated into the skin.

Test Example  5. Skin elasticity test

Skin elasticity effects were measured with the microdial patches of Examples 1 and 2.

The subjects were 10 healthy women without skin disease at 25 ° C, 50% RH and room temperature and humidity conditions. The subjects were divided into left and right eyes at the crows feet. For the right side, Example 2 was applied for 2 hours three times a week for 4 weeks, and fixed with a 3 M low-magnetic medical tape.

The elasticity of the skin was measured by Cutometer MPA580 (Courage and Khazaka, Kiln, Germany).

division R2 0 weeks 2 weeks 4 weeks Example 1 0.4035 + 0.1094 0.4284 + 0.0835 0.4612 + 0.1276 Example 2 0.4134 + 0.0421 0.4214 + 0.1134 0.4387 + 0.1327

The R2 value in Table 6 indicates the gross elasticity of the skin due to the ability to re-deform the skin.

As shown in Table 6 above, Example 1 showed an increase in the R2 value by 14.3%, and Example 2 showed an increase in the R2 value by 6.1%, which was effective in increasing skin elasticity.

Claims (11)

A herbal composition which has been heat-treated, including chrysanthemum, dermis, angelica, chrysanthemum, licorice root, licorice root, root, mint, peppermint, gardenia, musk and chest chest cartilage extract powder; Water soluble natural polymers; Natural thickener; And sterilized distilled water is coated on the surface of the micropipette. The herbal composition according to claim 1, wherein the herbal mixture comprises 1 to 100 parts by weight of the water-soluble natural polymer, 3 to 100 parts by weight of the natural thickening agent, and 100 to 700 parts by weight of sterilized distilled water, based on 100 parts by weight of the herbal composition. Fine spit. The herbal composition according to claim 1, wherein the herbal composition comprises 1 to 10% by weight of Seal, 1 to 15% by weight of Dermis, 5 to 20% by weight of Angelica japonica, 5 to 20% And 5 to 40% by weight of chick chest cartilage extract powder, wherein the chrysanthemum chondrodia extract powder is selected from the group consisting of 5 to 20% by weight of ginseng root, 5 to 20% by weight of ginseng, 5 to 20% by weight of ginseng, 1 to 10% by weight of peppermint, 1 to 10% Characterized in that the herbal composition is coated with a micro-needle. The microspheres coated with a herbal composition according to claim 1, wherein the microspheres coated with the herbal composition inhibit hyaluronidase activity. The herb composition according to claim 1, wherein the herbal mixture is coated to a thickness of 0.01 to 0.5 mm. The microspheres coated with a composition according to claim 1, wherein the microspheres are formed with a plurality of grooves. The microspheres coated with the herbal composition according to claim 1, wherein the water-soluble natural polymer is at least one selected from the group consisting of corn starch powder, sweet potato starch powder and rice flour. [2] The composition according to claim 1, wherein the natural thickening agent is at least one selected from the group consisting of oligosaccharides, fructose, maltose, honey and agar. The microspheres coated with a one-part composition according to claim 1, wherein the microspheres are titanium, titanium alloys or apatite ceramics. (a) crushing the seeds, dermis, Angelica grisea, Creation, Lycopodium, Lycopersiconum, Pueraria, Bacillus, Mint and Gardenia;
(b) preparing a herbal composition by adding musk and chest chest cartilage extract powder to the pulverized powder;
(c) mixing the herbal composition, the water-soluble natural polymer, the natural thickener, and the sterilized distilled water to prepare a herbal mixture;
(d) placing the herbal mixture in a mold, leaving the mixture under a vacuum pressure of -400 to -600 mmHg, and inserting a microspheres into a mold into which the herbal mixture is introduced; And
(e) drying the micro-needle-inserted mold at a temperature of 20 to 60 DEG C under a relative humidity of 20% or less to coat the micro-needle surface with the herbal mixture; and ≪ / RTI > [11] The method of claim 10, wherein the step (b) comprises mixing the herbal composition with sterilized distilled water at a weight ratio of 1: 2 to 5, To 30% to 90% of the total weight of the microspheres, and then filtering the microspheres.