KR20100110474A - A method of preparing a pharmaceutical formulation for treating burn - Google Patents

Abstract

PURPOSE: A method for manufacturing a pharmaceutical composition using natural materials for treating burn is provided to quickly heal burn without side effect and scar. CONSTITUTION: A method for manufacturing a pharmaceutical composition for treating burn containing complex herb extract as an active ingredient comprises: a step of inputting herbs into a pocket and sealing an entrance; a step of immersing the herb with 10-50 times of volume of water, low alcohol or mixture solvent for 30 minutes and 5 hours; a step of extracting at 90-120°C for 1-5 hours; a step of filtering the extract; a step of concentrating at 90-110°C; and a step of drying and pulverizing the concentrate at 40~70°C.

Description

A method of preparing a pharmaceutical formulation for treating burn

The present invention relates to a manufacturing method of a pharmaceutical preparation for burn treatment using natural materials, which is excellent in the treatment effect against burns. More specifically, the natural ingredients such as flower ginseng, scented herb, hyacinth, yellow wall and annual herb can be used to treat burns quickly and painlessly and without scars.

[Document 1] Korean Pharmacopoeia General Test Method

[Document 2] Korea Food & Drug Administration Notification No. 2007-61

[Document 3] Korea Food & Drug Administration Notification No. 2005-83

[Document 4] Food and Drug Administration Notice No. 2008-2

[Document 5] Korea Food & Drug Administration Notification No. 2008-23

[Document 6] Food and Drug Safety Notice No. 1998-130

Animal skin is the primary protective film that protects the living body from the external environment, and is affected by the external environment without filtration. Among these effects, damage caused by harmful pollutants such as air pollutants or ultraviolet rays is prominent. In the case of ultraviolet rays, an extremely small amount corresponding to 0.5% of the light reaching the earth, erythema, pigmentation, wrinkles and most skin cancers It is known to act as an inducing factor. Recently, due to the imbalance and destabilization of the ecosystem, the amount of ultraviolet rays reaching the surface is gradually increasing as the ozone layer in the atmosphere becomes thinner, and malignant melanoma increases by 0.6% as the ozone layer decreases by 1%. to be.

In general, when a body is injured, the organism has the property of defending itself to some extent and self-healing. If the skin is damaged, the skin damage below a certain level can be recovered by the self-healing ability, but the skin damage above a certain level may spread to other diseases due to other factors such as bacterial infection. In particular, when the skin is damaged by a burn due to ultraviolet rays or other fire substances, not only damage to skin tissue, but also additional damage caused by poisoning occurs, in order to treat this early, a wound treatment composition for burn treatment is used. The electrical composition should be excellent in biocompatibility, so that the rejection reaction at the wound site is small, it should be able to adhere closely to the wound site, the bacterial infection at the wound site should be prevented, and it should not be reactive even when mixed with other medicines. do.

Skin treatment compositions, which are currently used to aid in the treatment of burns and traumas, protect wounds for a limited time until the skin of Songsan recovers, prevent the leakage of moisture in the body, and absorb the fluid collected in the lesions when there is inflammation of the effusion. In addition, it shares the characteristics of preventing bacterial infection. Looking at them by type, a composition comprising a gel having excellent skin hygroscopicity, a composition comprising a polyurethane film or a freeze-dried product of pork skin, a composition comprising a porous membrane coated with chitin, a natural polysaccharide, a synthetic polymer or a functional gelatin The composition containing these as a main component, etc. are mentioned. In addition, wound healing compositions using other materials have been developed, but these include synthetic materials as the main ingredients, and these materials help to treat damaged areas of the skin, but side effects to normal tissues exist little by little. Therefore, in order to solve these problems, efforts have been made to develop wound healing compositions containing natural substances as main components. In recent years, it has been found that green tea extract is effective for the treatment of skin damage and skin diseases, and its active ingredient is reported to be a catechin compound, and development of a therapeutic composition using the same has been studied. However, the wound healing composition prepared from most natural products does not overcome the disadvantage that the cost of the material and the cost of the manufacturing process are enormous and economical.

In addition, in the case of using the composition for electrotherapy, it is generally applied directly to the wound, the burn requires a long treatment time and effort compared to the general wound. The reason for this is that the process of eliminating poison and the process of removing blisters caused by burns are additionally included. Thus, a treatment for burns is being developed separately from general wound treatments. However, the therapeutic agent thus developed can only prevent the recurrence of poison and blisters, and the removal of primary poison and blisters does not develop much in the traditional method.

Second-degree burns are burns up to the dermal layer of the skin. Blisters are formed, epithelial remnants and skin appendages form epithelium from the epithelium, which can heal. Pigmentation or depigmentation may occur, but generally no severe scars remain until the second-degree burn. .

Third-degree burns refer to burns of the epidermis and dermis, as well as the subcutaneous layer of the skin, with partial nerve palsy, in which the nerves are damaged and the pain is not felt properly. . Third-degree burns heal, form scars and heal scars, and skin grafts can reduce scar formation but are not complete.

In these burns, first-degree burns may be used as synthetic medicines and other natural ingredients, but in the case of 2-3-degree burns, sterile petrolatum gauze covers the wound and prevents secondary infection. Antibiotics such as penicillin and sulfamine were all applied, and it was not an exaggeration to say that there was no medicine for treating the wound by healing the wound, and the pain associated with the burn required a separate painkiller.

In addition, herbal burn treatments, which have been transmitted since ancient times, have been used. Generally, the herbal skin medicine materials described in the oriental medicine have seven kinds of minerals, such as sulfur, zeolite, sulfur, hard powder, podium, sensitized stone, borax, etc. There are two kinds of plants, and there are two kinds of plants such as saengpunggi and neck root skin, which have been appropriately selected and blended at a predetermined ratio, and have been used for the treatment of oriental surgical skin diseases.

Flower ginseng is a perennial herb that belongs to the Madibule family, which is native to western China, and is a well-known medicinal plant. Flower ginseng generally has a lowering action and is considered an anthraquinone glycoside as an active ingredient. In addition, medicinal and ginseng leaf ginseng have been shown to have antimicrobial activity in vitro against a large number of Gram-positive and several Gram-negative bacteria. Antibacterial active ingredient is mainly an anthraquinone derivative, the main action is bacterial inhibition and does not appear to have bactericidal action. Flower ginseng has also been studied as having an anti-tumor effect and has been shown to be inhibitory against melanoma and mammary gland. This is due to direct destruction of tumor cells. In addition, Hwasam has been shown to lower blood pressure, GI bleeding, landscaping.

Perennial herbaceous plants known as perennial herbaceous plants are anti-inflammatory and anti-allergic. Antiallergic activity of perfume plants has been shown to inhibit the release of allergens by inhibiting the enzyme activity system (SH-enzyme) of mast cells, which does not cause allergy and also has a direct relaxation effect on the smooth muscle itself. In addition, perfume plants have a relatively broad antimicrobial spectrum, antimicrobial action that inhibits all the bacilli, diphtheria bacilli, Pseudomonas aeruginosa, Staphylococcus aureus, meningococcal bacteria. In addition, perfume plants are antipyretic, coercive, diuretic, blood cholesterol and blood sugar lowering effect, edema, jingyeong, sedation, etc. There is no toxicity.

The pharmacological action known as perennial herbaceous plant includes antibacterial action and antipathogenic action. It has a relatively high inhibitory effect against hemolytic streptococci, meningitis, pneumococcal streptococci, cholera, anthrax, and staphylococcus aureus, and also inhibits erythrocytes, diphtheria bacteria, Bacillus subtilis, and green streptococci. In addition, cheonnyeon has a certain inhibitory effect against each type of influenza virus or Newcastle virus. In addition, cheonnyeon lowers blood pressure, strengthens the action of acetylcholine, relaxes vascular smooth muscle, stimulates smooth muscle of uterus, bladder, bronchus, stomach, etc., promotes bile production, anticancer, anti-radiation, etc. none.

Yellow wall is a deciduous arboretum, and in vitro experiments showed antimicrobial activity against Staphylococcus aureus, Pneumococcal, Diphtheria, Green Streptococcus, and Lycobacteria. This antimicrobial action is less than natural. In addition, the yellow wall has a blood pressure lowering action. Other actions include inhibitory effects on the central nervous system and no toxicity.

Yeonpyeoncho is a perennial herbaceous plant known as pharmacological action has a hemostatic action. This hemostatic action is related to the colloidal components contained in the beginning of the class and its action is considered to be physical. In addition, the annual salve has the treatment of gastric and duodenal perforation. In addition, the annual salary has a weak inhibitory effect on Mycobacterium tuberculosis.

In order to achieve the above object, the present invention provides a method for producing a pharmaceutical preparation for burn treatment containing a complex herbal extract as an active ingredient.

Hereinafter, a manufacturing method for obtaining a pharmaceutical preparation for burn treatment of the present invention will be described in detail.

A first step of weighing flower ginseng, perfumed plants, natural lotus, yellow wall, and annual herb, and putting the herbal medicine in the extracting cloth and blocking the entrance to the extracting device; 10 to 50 times the weight of the herbal medicine, preferably 10 to 20 times the water containing purified water, a lower alcohol having 1 to 4 carbon atoms such as methanol, butanol, or a mixed solvent thereof, preferably in water A second step of soaking for 30 minutes to 5 hours, preferably for 30 minutes to 2 hours; A third step of extracting the extracting apparatus at 90 to 120 ° C., preferably at 100 to 110 ° C. for 1 hour to 5 hours, preferably 1 hour to 3 hours; A fourth step of leaving the extract for 10 minutes to 1 hour, preferably 20 to 40 minutes, and then filtering the extract with a mesh; The filtered extract is concentrated in a bath at 90 to 110 ° C., preferably 100 to 110 ° C .; The concentrated herbal extract may be obtained through the sixth step of manufacturing the powder by gradually drying the powder at 40 to 70 ° C., preferably 50 to 60 ° C., and then pulverizing to obtain the complex herbal extract of the present invention (hereinafter referred to as “SS”). Can be.

The pharmaceutical preparation of the present invention Purified water and propylene glycol were added to a stainless container, and the above-obtained SS was dissolved while maintaining 30 to 100 ° C, preferably 40 to 70 ° C. A first step of preparing an aqueous phase by holding it in place; Put hard flow paraffin in the stainless container and warmed to 60 to 100 ℃, preferably 70 to 90 ℃, stearyl alcohol, cetanol, polysorbate 60 and 60 to 100 ℃, preferably 70 to 90 A second step of dissolving the solution while maintaining the temperature at 50 ° C., then adding methyl paraoxybenzoate and propyl paraoxybenzoate while stirring at 50 to 100 rpm, preferably 40 to 70 rpm to prepare an oil phase; The oil phase obtained above was filtered through 100 mesh and placed in a preparation tank containing the water phase. For 30 minutes at 1000 to 3000 rpm, preferably 2000 to 3000 rpm, 50 to 90 ° C, preferably 75 to 85 ° C with a homomixer A third step of emulsifying for 2 hours, preferably 45 to 75 minutes, and then degassing under reduced pressure; The cooling water is opened and cooled with stirring at 30 to 100 rpm, preferably 20 to 50 rpm, until it reaches 10 to 50 ° C, preferably 20 to 40 ° C. After cooling starts, run the homomixer for 10 minutes and reduce the pressure for 15 minutes. After cooling, the cream is checked and the yellow cream (hereinafter referred to as a fourth step) is left for 8 to 24 hours, preferably 10 to 15 hours, while maintaining a temperature of 10 to 50 ° C, preferably 20 to 40 ° C. Named 'CR').

The present invention provides a pharmaceutical preparation for burn treatment comprising the complex herbal extract obtained by the above method as an active ingredient.

The pharmaceutical preparations defined herein are complex herbal extracts: hard fluid paraffin: stearyl alcohol: propylene glycol: polysorbate 60: monostearate sorbitan: paraoxybenzoic acid methyl: paraoxybenzoic acid propyl: cetanol 1 to 1 45: 50-150: 20-50: 100-150: 15-35: 15-35: 0.1-5: 0.1-5: 20-50 mixing ratio (w / w%), Preferably 20-35: 100 ~ 140: 25 ~ 45: 110 ~ 140: 20 ~ 30: 20 ~ 30: 0.5 ~ 2: 0.5 ~ 2: It is characterized in that the pharmaceutical formulation having a mixing ratio (w / w%) of 25 to 45.

Complex herbal extracts as defined herein are characterized in that the complex herbal extracts, including flower ginseng, fragrance myelin, natural lotus, yellow wall and annual herb.

The compound herbal extract defined herein is a dry weight ratio of flower ginseng: perfume plant: natural lotus: yellow wall: annual salary: 1-5: 1-5: 1-5: 1-5: 1-5 mixed ratio (w / w%), Preferably the mixing ratio (w / w%) of 1-3, 1-3: 1-3, 1-3: 1-3, More preferably, 1-2: 1-2: 1-2: 1-2 : Characterized in that the compound herbal extract having a mixing ratio (w / w%) of 1-2.

Extracts as defined herein include water, including purified water, lower alcohols having 1 to 4 carbon atoms, such as methanol, methanol, butanol, or a solvent selected from a mixed solvent thereof, preferably extracts available in water.

The pharmaceutical preparation for burn treatment according to the present invention configured as described above may be formulated in a conventional pharmaceutical formulation known in the art, but is suitable for the treatment of burns, more specifically, in the form of ointments, creams, gauze, etc. Systemic coating formulation.

In addition, the pharmaceutical preparation for burn treatment of the present invention can be used in medicine in human and veterinary fields, and the formulation and its components should be pharmaceutically acceptable.

The pharmaceutical preparation for the treatment of burns of the present invention is characterized in that it comprises 0.1 to 50% by weight, preferably 0.5 to 30% by weight of the complex herbal extract.

Pharmaceutical preparations for burn treatment containing the complex herbal extract of the present invention as an active ingredient include a pharmaceutically acceptable binder (e.g., polyvinylpyrrolidone, hydroxypropylcellulose), a disintegrant (e.g., carboxymethyl cellulose water) Calcium, sodium starch glycolate), diluents (e.g. corn starch, lactose, soybean oil, crystalline cellulose, mannitol), glidants (e.g. magnesium stearate, talc), stabilizers (sodium carboxymethylcellulose, alpha or beta cyclodextrins, vitamins C, citric acid, white lead), preservatives (e.g. methyl paraoxybenzoate, paraoxybenzoic acid filaments, sodium benzoate) or flavors (e.g. ethyl vanillin, masking flavor, menthol flavono, herbal flavor) It may be prepared as a pharmaceutical preparation, such as a film, powder, gel, ointment, cream, liquid. In addition, in order to prevent further dermal infection by external infectious bacteria, it may further comprise a normal dose of known antibiotics.

The complex herbal extract of the present invention can be used as a pharmaceutical preparation for burn treatment with excellent effects such as eliminating pain in a short time, a very short healing period, and leaving no scars.

Hereinafter, the present invention will be described in more detail with reference to the following examples and experimental examples.

However, the following Examples and Experimental Examples are only for illustrating the present invention and do not limit the scope of the present invention.

Example 1. Preparation of Complex Herbal Extract

Weigh ginseng, perfumed plants, natural lotus, yellow wall, and annual herb weigh 100 kg each, and then put the herbal medicine in the extraction bag and block the entrance to put it in the extractor. Add 15 times the weight of the herbal medicine and immerse for 1 hour. Extraction is performed at 95 ° C. for 2 hours in an extraction apparatus. After leaving for 30 minutes after extraction, the extract is passed through No. 140 (106 μm). The residue is discarded and the filtered extract is concentrated to a hot bath below 95 ° C to give a final concentration of 500 L. The concentrated solution was slowly dried at 60 ° C. or lower, pulverized and powdered, and passed through No. 40 (425 μm) to prepare a brown powder sample (hereinafter referred to as “SS”) of the present invention.

Preparation Example 1 Preparation of Cream

1-1. Award manufacturing

Put a suitable amount of purified water and 121.4 mg of propylene glycol (Samjeon Pure Chemical Co., Ltd.) in a stainless steel container, and dissolve it by adding 30 mg of SS obtained in Example 1 while maintaining 55 to 60 ° C.

1-2. Paid manufacturing

111.7 mg of hard liquid paraffin (Samjeon Pure Chemical) in a stainless steel container, warmed to 75-80 ° C, 37.9 mg of stearyl alcohol (Samjeon Pure Chemical), 37.9 mg of cetanol (Samjeon Pure Chemical), polysorbate 60 (Samjeon Pure Chemical) 25.2 Add mg, 25.2 mg of sorbitan monostearate (Samjeon Pure Chemicals), and dissolve while maintaining at 75-80 ° C, and further add 1 mg of paraoxybenzoic acid methyl (ACROS) while stirring at 60 rpm, and propyl paraoxybenzoic acid (ACROS). Add 1 mg to dissolve.

1-3. Blending and emulsifying

The oil phase obtained in Preparation Example 1-2 was filtered through 100 mesh and placed in a steam kettle containing the aqueous phase obtained in Preparation Example 1-1 at 80 ° C. while operating a stirrer (Sungsung) at 40 rpm. Emulsify for 60 minutes (at this time 30 minutes at 80 ° C, 2700 rpm for homomixer). After emulsification, degassing under reduced pressure.

1-4. Cooling

Open the cooling water and cool it with stirring at 40 rpm until it reaches 30 ° C. Start the homomixer for 10 minutes after the start of cooling, and depressurize for 15 minutes after the start of cooling. After cooling, the state of the cream was confirmed and left overnight while maintaining 30 ° C. to obtain a yellow homogeneous cream, which was used as a sample of the following experimental example (hereinafter referred to as 'CR').

Preparation Example 2 Preparation of Vaseline

100 g of SS and 100 g of petrolatum obtained in Example 1 were kneaded and stirred to obtain petrolatum, which was used as a sample of the following experimental example (hereinafter referred to as 'V').

Experimental Example 1. General Analysis Test

1-1. Dry weight loss test

Using the sample obtained in the above example, the drying loss test was performed according to the method of the document (Dry Loss Test Method of the Korean Pharmacopoeia General Test Method herbal medicine test method).

The weighing bottle is dried for 30 minutes according to the method prescribed in each article of medicine, and the mass is precisely weighed. 2 g of SS obtained in Example 1 was previously weighed into a weighing bottle, weighed precisely, dried at 105 ° C. for 5 hours, cooled in a desiccator (silica gel), and weighed precisely. It was again dried at 105 ° C., and weighed precisely every hour, and the weight loss at the time of yield was shown in Table 1 below as drying loss (%).

Tare Weight (g) Sample amount (g) Weight after test (g) Loss of drying Average 25.0232 2.0002 26.8608 8.13% 8.30% 23.8183 2.0003 25.6513 8.36% 25.2292 2.0004 27.0616 8.40%

As a result of the experiment, it was confirmed that the drying loss of SS obtained in the above example was 10% or less.

1-2. Batch test

Using the sample obtained in the above example, the batch test was carried out according to the method of the literature (Korean Pharmacopoeia General Test Method Herbal Test Method Batch Method).

Platinum, quartz or fructose crucibles are preheated at 500 to 550 ° C for 1 hour, left to cool, and then weighed precisely. 2 g of the SS obtained in Example 1 was precisely weighed and placed in the crucible, and the mass thereof was precisely weighed.If necessary, the lid of the crucible was covered or placed at an angle, and then slightly heated. Painting until no carbide remains. Allow to cool, then weigh the mass precisely. The residue was incubated again until it became a constant amount, left to cool, and then weighed precisely to determine the mass (%) as shown in Table 2 below.

Tare Weight (g) Sample amount (g) Weight after test (g) Ash quantity Average 31.1552 2.0002 32.3222 8.35% 8.31% 32.2860 2.0003 32.4523 8.31% 31.8666 2.0004 32.0319 8.26%

As a result, it was confirmed that the ash content of SS obtained in Example 1 was 10% or less.

1-3. X content test

Using the sample obtained in the above example, the X content test was performed according to the method of the literature (Korean Pharmacopoeia General Test Method Herbal Medicine Test Method Dilute Ethanol X Assay).

2.3 g of SS obtained in Example 1 was precisely weighed and placed in a suitable flask, and 70 ml of dilute ethanol was added and shaken occasionally to leach for 5 hours. It is left for 16 to 20 hours and then filtered. The flask and residue are washed with dilute ethanol until the filtrate is 100 ml. 50 ml of the filtrate is evaporated to dryness in a water bath, dried at 105 ° C. for 4 hours and cooled in a desiccator (silica gel). The mass is precisely weighed and multiplied by 2 to obtain the amount of diluted ethanol. The X content (%) of the sample amount converted into the dry matter was calculated from the value obtained from the drying loss, and is shown in Table 3 below.

Tare Weight (g) Converted to dry matter
Sample weight (g) Weight after test (g) X content Average 103.3103 2.1093 104.7942 70.35% 70.35% 103.0385 2.1092 104.5200 70.24% 104.6155 2.1091 106.1017 70.47%

As a result, the X content of the SS obtained in Example 1 was confirmed that the dilute ethanol x 75% or less.

1-4. Mass deviation test

Using the sample obtained in the preparation example, the mass deviation test was carried out according to the method of the literature (mass (dose) deviation standard and test method of the drug No. 2007-61 of the Food and Drug Safety Notice).

With the ten preparations obtained in Preparation Example 1, the outer surface of the container is washed and dried thoroughly, and then the individual masses are precisely weighed. The individual numbers should be identified, for example, by recording each number, so that each product and its mass correspond, completely remove the contents, rinse and dry, and then empty container mass (including any accessories that were weighed together when first weighed). Precisely. The mass of the content is subtracted from the mass of the corresponding empty container, and is shown in Table 4 below.

Sample Mass (g) Average mass (g) Mass deviation No.1 20.02 20.02 0.06% No.2 20.13 No.3 19.95 No.4 19.98 No.5 20.01 No.6 20.02 No.7 19.98 No.8 20.13 No.9 20.01 No.10 20.04

Experimental results, it was confirmed that the mass deviation of the formulation obtained in Preparation Example 1 was 0.06%.

Experimental Example 2. Content Test

Liquid chromatographic experiments were performed using the samples of the above examples.

2-1. Berberine content test

0.5 g of SS obtained in Example 1 was precisely weighed, and 30 ml of methanol and diluted hydrochloric acid (100: 1) were added thereto, and a reflux condenser was attached, heated in a water bath for 30 minutes, cooled, and filtered. The residue is repeated twice with 30 ml of methanol and dilute hydrochloric acid (100: 1) and 20 ml. Add 10 ml of methanol to the last residue, shake well and filter. Combine all the filtrates and add methanol to make exactly 100 ml. Separately, about 10 mg of berberine chloride standard is precisely weighed and dissolved in methanol to make exactly 100 ml. 10 μl of the sample solution and the standard solution were accurately taken and tested according to the liquid chromatograph method under the conditions shown in Table 5 below. The peak areas A _T and A _S of the sample solution and the standard solution were measured according to the following Equation 1.

Amount of berberine (C ₂₀ H ₁₈ NO ₄ ) (mg)

= Amount of berberine chloride standard in terms of anhydride (mg) × A _T / A _S × 0.9047

_{0.9047: (C 20 H 18 NO} 4 / C 20 H 18 NO 4 · HCl) = (336.37 / 371.82)

In addition, accurately weigh 10 g of CR obtained in the above Preparation Example, add 75 ml of methanol and dilute hydrochloric acid (100: 1), attach a reflux condenser, heat for 30 minutes in a water bath, and cool. The residue is repeated twice with 75 ml of methanol and dilute hydrochloric acid (100: 1) and 50 ml. Add 25 ml of methanol to the last residue, shake well, and filter. All the filtrates were combined and added to methanol to make the sample solution exactly 250 ml, and the peak areas A _T and A _S of the sample solution and the standard solution were measured in the same manner as described above.

Amount of berberine (C ₂₀ H ₁₈ NO ₄ ) (mg)

= Amount of berberine chloride standard in terms of anhydride (mg) × A _T / A _S × 0.9047 × 2.5

_{0.9047: (C 20 H 18 NO} 4 / C 20 H 18 NO 4 · HCl) = (336.37 / 371.82)

division Condition Detector Ultraviolet absorption spectrophotometer (wavelength 345 nm) column Filling stainless steel pipes with a diameter of 4 to 6 mm and a length of 15 to 25 cm, octadecylsilyl silicacagel for liquid chromatography of 5 to 10 μm Column temperature 30 ℃ Mobile phase To 1000 ml of water and acetonitrile mixture (1: 1), add 3.4 g of potassium dihydrogen phosphate and 1.7 g of sodium lauryl sulfate to dissolve flux Adjust the berberine retention time to about 11 minutes

As a result, as shown in Figure 1, when quantifying the SS 1 g obtained in Example 1, the amount of berberine (C ₂₀ H ₁₈ NO ₄ ) in the SS 1 g is more than 10.5 mg, as shown in Figure 2 When quantifying CR obtained in Preparation Example 1, the amount of berberine (C ₂₀ H ₁₈ NO ₄ ) in 1 g of CR obtained in Preparation Example 1 was confirmed to be 0.32 mg or more.

2-2. Baikalin content test

0.5 g of SS obtained in the above example was precisely weighed, and 30 ml of a mobile phase was added thereto, followed by a reflux cooler, and heated in a water bath for 30 minutes. After cooling, transfer to a centrifuge tube and centrifuge to obtain supernatant. Put 30 ml of mobile phase into the refluxed container, wash, transfer the washed solution to the centrifuge tube, shake for 5 minutes, mix, and centrifuge to take the supernatant. Add 30 ml of mobile phase to the residual radish, shake well for 5 minutes, and centrifuge to take supernatant. Combine the extracts and add the mobile phase to exactly 100 ml. Take 2 ml of this solution correctly and add the mobile phase to make 20 ml exactly as the sample solution. Separately, weigh 10 mg of the Baikal standard accurately and add methanol to make exactly 20 ml. Take exactly 2 ml of this solution and use 20 ml of the mobile phase as the standard solution. The test solution and 20 μl each of the standard solution were tested according to the liquid chromatography method under the conditions shown in Table 6 below._T And A_SWas measured according to the following equation (3).

Amount of Baikal (C ₂₁ H ₁₈ O ₁₁ ) (mg)

= Amount of Baikal standard (mg) × A _T / A _S × 5

In addition, CR 5 g obtained in Preparation Example 1 by the same experimental method as above.

Baikal peak areas A _T and A _S were measured according to the following equation (4).

Amount of Baikal (C ₂₁ H ₁₈ O ₁₁ ) (mg)

= Amount of Baikal standard (mg) × A _T / A _S × 1.25

division Condition Detector Ultraviolet absorption spectrophotometer (wavelength 277 nm) column Filling stainless steel pipes with a diameter of 4 to 6 mm and a length of 15 to 25 cm, octadecylsilyl silicacagel for liquid chromatography of 5 to 10 μm Column temperature Constant temperature around 50 ℃ Mobile phase Dilute phosphoric acid (1 → 146), acetonitrile mixture (18: 7) flux Adjust the Baikalin retention time to about 7 minutes

As a result, as shown in Figure 3, when quantifying the SS obtained in Example 1, Baikal (C ₂₁ H ₁₈ O ₁₁ : 446.37) in the SS 1g contains more than 40 mg, shown in Figure 4 As described above, when quantifying the CR obtained in Preparation Example 1, it was confirmed that the bicalin contained 1.2 mg or more in 1 g of CR.

Experimental Example 3. Microbial Test

Using the SS obtained in the above examples and the CR obtained in the preparation example, the microbial experiment was carried out according to the experimental method described in the literature (microbial limit standards and test methods of the 2005-83 pharmaceutical products, etc. when the Food and Drug Safety Notification).

As a result of the test, as shown in Figure 5, 6 and Table 7, it can be confirmed that both the SS obtained in Example 1 and the CR obtained in Preparation Example 1 was not detected microorganisms.

Item Microbial Test Criteria Test result CR Germ: 1x10 ² cfu / g
Fungus: 10 cfu / g
Specific bacteria: Not detected  Not detected SS Germ: 1x10 ⁵ cfu / g
Fungus: 1x10 ² cfu / g
Specific bacteria: Not detected  Not detected

Experimental Example 4 Heavy Metal Test

The sample obtained above was subjected to the heavy metal test in accordance with the experimental method described in the literature (Heavy metal acceptance criteria and test method of herbal medicines, etc. No. 2008-2, Food and Drug Safety Notice No. 2008-2).

4-1. Lead, Arsenic, Cadmium Heavy Metal Test

0.5 g of SS obtained in Example 1 was accurately weighed, and placed in a microwave sample preparation device-only container, and 12 ml of nitric acid was added thereto. If the degradation is poor, add 1-2 ml of hydrochloric acid or 30% hydrogen peroxide. The vessel is placed in a hood to remove off-gases and disassembled using a microwave sample preparation device. After the decomposition is completed, the decomposition solution is filtered through filter paper to prepare a sample solution. Separately, 12 ml of nitric acid is placed in a microwave sample preparation device-only container and operated in the same manner as in the preparation of the sample solution.

The test solution, standard solution and blank test solution shall be measured according to the Atomic Absorption Spectrophotometry in the Korean Pharmacopoeia General Test Methods. Atomic Absorption Spectrophotometer Dilute standard stock solution (1000 mg / L) for atomic absorption analysis of each heavy metal to the appropriate concentration using 0.5 mol / L nitric acid, prepare calibration curve and calibrate with blank test solution ) Was measured.

4-2. Mercury heavy metal test

500 mg of SS obtained in Example 1 was accurately weighed and measured using a mercury analyzer.

 Item  Heavy Metal Test Standard  Test result  SS  30 ppm or less  1.0 ppm

As a result of the experiment, as shown in Table 8, the lead, arsenic, cadmium, mercury, etc., based on the heavy metal test criteria of 30 ppm or less, it was confirmed that the SS obtained in Example 1 was 1.0 ppm.

Experimental Example 5. Residual Pesticide Test

The sample obtained in the above Example was subjected to the heavy metal test in accordance with the experimental method described in the document (based on the herbal extracts of Table 1 of Annex 1 of 2008 Food and Drug Safety Notice No. 2008).

5-1. Preparation of Residual Pesticide Test Test Solution

1) Extract

500 g of SS obtained in Example 1 was pulverized well, weighed about 5 g, 40 ml of water was added and left for 4 hours. Add 90 ml of acetone to it and homogenize for 5 minutes with a homogenizer. Filter under reduced pressure with a vacuum pump, a Erlenmeyer flask and a Buchner funnel. Transfer the filtrate to a 500 ml separatory funnel and add 50 ml of saturated brine and 100 ml of distilled water. Add 70 ml of dichloromethane, shake it vigorously, and stand still to separate the layers. The lower layer (dichloromethane layer) is collected in another separatory funnel. Add 70 ml of dichloromethane to the water layer again, shake it vigorously, and stand still to separate the layers, then collect the lower layer (dichloromethane layer). The dichloromethane layer is dehydrated through anhydrous sodium sulfate, concentrated in a vacuum condenser, and dissolved in 4 ml of hexane.

2) tablets

6 ml of hexane was added to a furrysil cartridge (6 ml, 1 g) in advance, stopped for 2 minutes, and then drained. 6 ml of 20% acetone-containing hexane was spilled in the same manner as above. The extract is then placed on top of the cartridge and allowed to rest on the column for 2 minutes and then slowly receive the effluent. Collect the effluent by distilling out with 5 ml of hexanedichloromethane acetone (50: 48.5: 1.5) while the cartridge is wet with solvent. The distillate is concentrated under reduced pressure in a water bath (below 40 ℃), blown off the solvent, and dissolved in 2 ml of 20% acetone-containing hexane to prepare a test solution.

5-2 Analysis Conditions

1) Detector: GC-ECD

2) Column: A silicate glass capillary column tube with a diameter of 0.25 mm and a length of 30 m. 3) Coated 5% methyl silicon for gas chromatograph with a thickness of 0.25 μm, with a diameter of 0.25 mm and a length of 30 m. Coated capillary column tubes coated with 50% phenyl, 50% methylsilicone for gas chromatograph at a thickness of 0.25 μm or equivalent

3) Column temperature: Inject the sample at 80 ° C, hold for 2 minutes, and raise the temperature to 280 ° C at a rate of 10 ° C per minute and hold for 10 minutes or more.

4) Injection part temperature: 260 ℃ split mode (10: 1)

5) Detector temperature: 280 ℃

Item Residual Pesticide Test Criteria Test result SS Total BHC 0.2ppm 0.0 ppm Total DDT 0.1 ppm 0.0 ppm Adrin, Endrin, Dieldrin 0.01 ppm 0.0 ppm

Experimental Example 6. Preservative Test

The preservative test of CR obtained in Preparation Example 1 was carried out according to the literature (preservative standards and test methods in the pharmaceutical products No. 1998-130 of the Food and Drug Safety Notice) as follows.

The final concentration of the preservative is 10 µg in 1 ml and filtered. The filtrate is used as the sample solution. The standard solution was precisely weighed with the paraoxybenzoic acid methyl standard and the paraoxybenzoic acid propyl standard, and the methanol was added to make 10 ㎍ of 1 ml of the final concentration. The amount of preservative was measured in accordance with 5.

Amount of Preservative (mg) = Amount of Standard Solution (mg) XA _T / A _S

division Preservative Test Analysis Conditions Detector UV Absorbance Spectrometer (254 nm) column A stainless steel tube of about 4.6 mm in diameter and 25 cm in length was filled with octadecylsilylated silica gel for liquid chromatograph of 5 µm. Mobile phase 50% methanol flux 0.5 ml / min

Item Preservative Test Condition Preservative Test Results CR 80 to 120% of display Paraoxy aromatic acid methyl (1 mg / g) 98.4% Propyl paraoxyacetic acid (1 mg / g) 98.6%

As a result, it was confirmed that paraoxybenzoic acid methyl (C ₈ H ₈ O ₃ ) and paraoxybenzoic acid propyl (C ₁₀ H ₁₂ O ₃ ) in CR obtained in Preparation Example 1, the content is 80 to 120% of the standard solution I could confirm that.

Experimental Example 7. Burn Treatment

CR obtained in Preparation Example 1 was cleared to various burn patients, spread 4 g three times a day and applied to the affected area as a result of treatment days compared to patients who applied conventional burn ointment the same number of times And in the pain reduction portion of the patient. The results of these clinical trials are shown in Table 12 below.

Burn accuracy When applying an existing ointment When applying CR Treatment staff (person) Healing days (days) Pain Treatment staff (person) Healing days (days) Pain Second degree burns 12 6 has exist 18 2 none 8 8 has exist 3 3 none Third degree burns 5 40 has exist 15 20 none 15 50 has exist 4 30 none 5 60 has exist One 35 none

Experimental results, as shown in the table, it can be seen that the CR obtained in Preparation Example 1 shows a faster and better therapeutic effect than the conventional ointment applied.

1 is a diagram showing a berberine content test chromatogram of Example 1 SS,

2 is a diagram showing a berberine content test chromatogram of Preparation Example 1 CR,

Figure 3 is a diagram showing the chromatin content test chromatogram of Example 1 SS,

4 is a diagram showing a chromatin content test chromatogram of Preparation Example 1 CR,

5 is a view showing a microorganism test result of Example 1 SS,

6 is a view showing a microorganism test result of Preparation Example 1 CR.

Claims (6)

A method of preparing a pharmaceutical preparation for burn treatment containing a complex herbal extract including flower ginseng, scented myrtle, medicinal herb, yellow wall, and annual herb as an active ingredient. The method of claim 1, wherein the complex herbal extract is a first step of weighing flower ginseng, perfume plant, medicinal herb, yellow wall and annual herb, and then placing the herbal medicine in an extract cloth and blocking the inlet into the extracting device; A second step of immersing in a solvent selected from C1-4 lower alcohols such as water, methanol, butanol and the like, or a mixed solvent thereof, including purified water of 10 to 50 times the weight of the herbal medicine, and soaking for 30 minutes to 5 hours; A third step of extracting the extracting apparatus at 90 to 120 ° C. for 1 hour to 5 hours; A fourth step of leaving the extract for 10 minutes to 1 hour and then filtering the extract with a mesh; The filtered extract is concentrated in a bath at 90 to 110 ° C. in a fifth step; Method of producing a pharmaceutical formulation comprising the sixth step of manufacturing the concentrated solution by gradually drying the powder at 40 to 70 ℃ and pulverized. The method of claim 2, wherein the complex herbal extract is a dry weight ratio of flower ginseng: perfumery myelin: natural lotus: yellow wall: annual grade is 1-5: 1-5: 1-5: 1-5: 1-5 mixed ratio (w / w Method for preparing a pharmaceutical formulation, characterized in that the compound herbal extract having a%). The method of claim 2, wherein the extract comprises a solvent selected from water including purified water, lower alcohols having 1 to 4 carbon atoms such as methanol, methanol, butanol, or a mixed solvent thereof. The method according to claim 1, wherein the preparation method is dissolved in a mixed tank containing purified water and propylene glycol in a stainless container, and put the mixed herbal extracts including flower ginseng, perfume plants, cheonnyeon, yellow wall and annual herb while maintaining 30 to 100 ℃, and put into a preparation tank A first step of preparing an aqueous phase by maintaining at 50 to 100 rpm; The hard fluidized paraffin is placed in the stainless steel container and heated to 60 to 100 ° C., and then stearyl alcohol, cetanol, and polysorbate 60 are added and dissolved at 60 to 100 ° C., followed by stirring at 50 to 100 rpm. Paraoxybenzoic acid methyl and paraoxybenzoic acid propyl to dissolve to prepare an oil phase; A third step of filtering the oil phase obtained above to 100 mesh and emulsifying it in a preparation tank containing the aqueous phase and emulsifying at 1000 to 3000 rpm and 50 to 90 ° C. for 30 minutes to 2 hours, followed by degassing under reduced pressure; Open the cooling water and cool it while stirring at 30-100 rpm until it becomes 10-50 degreeC. After cooling starts, operate homomixer for 10 minutes and depressurize for 15 minutes. Method of manufacturing a pharmaceutical formulation comprising the fourth step of the manufacturing process to confirm the state of the cream after cooling and left for 8 to 24 hours while maintaining 10 to 50 ℃. 6. The pharmaceutical preparation according to claim 5, wherein the pharmaceutical preparation of claim 1 is a complex herbal extract of claim 1: hard liquid paraffin: stearyl alcohol: propylene glycol: polysorbate 60: monostearate sorbitan: paraoxybenzoic acid methyl: paraoxybenzoic acid propyl: cetanol Pharmaceutical formulation having a mixing ratio of 1 to 45: 50 to 150: 20 to 50: 100 to 150: 15 to 35: 15 to 35: 0.1 to 5: 0.1 to 5: 20 to 50 Method for producing a pharmaceutical formulation characterized in that.

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