KR20210150829A - Composition for treating of rhinitis comprising Angelica gigas extracts and indirubin - Google Patents

Abstract

The present invention relates to a composition for the treatment of psoriasis or rhinitis, comprising an Angelica gigas extract and an indirubin concentrate. More specifically, the present invention relates to a composition for treating psoriasis or rhinitis, which is particularly effective for the treatment of atopic dermatitis, rhinitis accompanied by psoriasis, and the like by including 0.01 to 5 w/v% of the Angelica gigas extract and 0.01 to 5 w/v% of the indirubin concentrate.

Description

Composition for treating psoriasis or rhinitis comprising Angelica gigas extracts and indirubin, comprising Angelica gigas extracts and indirubin concentrate

The present invention relates to a composition for treating rhinitis, comprising an extract of Angelica keiskei and indirubin concentrate.

Rhinitis refers to inflammation of the so-called nasal mucosa, and pathologically, it is a leaching inflammation, and among them, purulent inflammation and allergic inflammation can be seen a lot. In either case, it is characterized by leaching of liquid components from blood vessels, edema, cell leaching and hypersecretion.

The types of rhinitis vary depending on the cause and symptoms such as acute rhinitis, chronic rhinitis, allergic rhinitis, etc. Irritant rhinitis and others are classified into 4 categories: 1) acute or chronic infectious rhinitis, 2) allergic rhinitis, non-allergic rhinitis, rhinorrhea, congestive rhinitis, and hypersensitivity non-infectious rhinitis such as dryness, 3) physical and chemical , irritant rhinitis caused by stimuli such as radioactive substances, and 4) other atrophic rhinitis.

Infectious rhinitis can be divided into acute rhinitis and chronic rhinitis with short-term symptoms called rhinitis. Infective chronic paranasal sinusitis, which has lesions in the nasal cavity centered on the ethmoid sinus and middle nasal passages, is also included in the infectious rhinitis. Among infectious rhinitis, acute rhinitis is mainly caused by a cold caused by an infection such as a viral infection, but acute rhinitis is also common. Acute viral rhinitis (cold) is characterized by symptoms such as runny nose, nasal congestion, post nasal drip, cough, and mild fever. In order to relieve nasal congestion, a vasoconstrictor such as a spray-type nasal drop of phenylephrine or oral medicine of pseudoephedrine is used. However, the use of sprays needs to be limited to within 3 to 4 days due to side effects such as nasal congestion, and antihistamines have an effect of suppressing rhinorrhea (runny nose), but drowsiness may occur.

Factors that cause simple acute rhinitis include hypersensitivity or inflammatory reaction caused by dust, soot, tobacco, air pollution, and temperature changes, dryness, and moisture. Symptoms, which start with sneezing, are olfactory disturbances due to nasal obstruction (stuffy nose) and runny nose. The nasal mucosa is congested and, if swollen, usually heals within 10 days. In the case of bacterial infection, the symptoms accompanying fever worsen and develop into sinusitis or chronic rhinitis over time. Symptomatic treatment methods are often used. Antipyretics, analgesics, antitussives, and anti-inflammatory drugs are used. In case of bacterial infection, antibiotics are used. In addition, it is helpful to maintain psychological stability or warmth.

Chronic rhinitis is usually accompanied by chronic sinusitis in many cases. There are three types of chronic rhinitis, which are called chronic simplex rhinitis, chronic hypertrophic rhinitis, and atrophic rhinitis, respectively. Chronic simplex rhinitis is a condition in which the nasal mucosa is chronically swollen as a result of repeated acute rhinitis. The symptoms of chronic simplex rhinitis are largely the same as those of chronic hypertrophic rhinitis, and nasal obstruction, rhinorrhea, olfactory disturbance, and headache appear. However, it is different from chronic hypertrophic rhinitis in that swelling (swelling) of the nasal mucosa is improved by vasoconstrictors. Conservative treatments such as application of drugs and use of anti-inflammatory agents are also performed, but the most important treatment is to remove the inducements.

Complex type (nose hypersensitivity) rhinitis usually has multiple symptoms such as runny nose, stuffy nose, and sneezing. House dust, mites, mold, various bacteria, volatile irritants, leaves, pollen, grass, animal hair, etc. are causative substances of allergic rhinitis. Allergic rhinitis, a type I allergic disease, often has allergic predisposition such as a history of allergy, complications, and family history, and is characterized by increased focal mast cells and eosinophils, elevated serum-specific IgE levels, and non-specific hypersensitivity of the mucous membrane. .

Among non-allergic rhinitis, essential rhinitis is a type of chronic rhinitis, and although the symptoms are similar to those of allergic rhinitis, it refers to rhinitis for which no clear antigen is recognized.

Rhinitis is a chronic disease that generally has the main symptoms of runny nose and nasal congestion, which are accompanied by congestion, inflammation and swelling of the mucous membrane of the nose, and interferes with daily life.

Drugs generally used for drug therapy can be classified into drug groups such as steroids, histamine receptor antagonists, chemical mediator release inhibitors, thromboxane A2 receptor antagonists, thromboxane A2 synthesis inhibitors, leukotriene antagonists, and Th2 cytokine inhibitors. Steroids or histamine receptor antagonists are frequently used as therapeutic agents for mild allergic rhinitis, and steroids and histamine receptor antagonists are used in combination for severe cases.

The main disadvantages of steroids for nasal spray include local side effects such as burning nose, nasal irritation, nasal dryness, and nasal bleeding. Although antihistamines suppress allergic symptoms, they have drawbacks such as drying the nasal mucosa and causing drowsiness. In addition, the allergen reduction method shows an effect on hypersensitivity reaction, but has a disadvantage in that a low dose must be injected for a long time. Therefore, there is a demand for the development of a new rhinitis treatment with high efficacy, few side effects, and low recurrence rate in rhinitis patients.

On the other hand, cytokines related to allergic inflammatory diseases reduce the proliferation rate of skin keratinocytes and inhibit the matrix formation of the dermal layer, thereby slowing the healing rate of damaged skin, such as skin aging, atopic dermatitis, psoriasis, etc. Causes inflammatory skin disease.

In particular, among skin diseases related to inflammation and immune abnormalities, psoriasis is a relatively common skin disease that occurs in 1-2% of the world's population, shows various clinical symptoms, and is a chronic disease that repeats exacerbation and improvement. The exact cause of psoriasis is not known, but so far it is considered an autoimmune disease. In other words, the hypothesis that psoriasis lesions are caused by the interaction between keratinocytes in the epidermis and cells such as T cells and fibroblasts in the dermis is accepted (Nickoloff, B.J., 1999). In addition, a recent study revealed that keratinocytes secrete TNF-α and IL-8 mediating the onset of psoriasis by activating the NF-κB (nuclear factor-κB) signaling system through TLR (toll-like receptor). It has been confirmed that keratinocytes play an important role in the pathogenesis of psoriasis, and it is reported that psoriasis therapeutics can be developed through the immunomodulatory function of keratinocytes (Li, ZJ, et al., 2013).

Until now, steroids for maintaining moisture in the skin and regulating the inflammatory response of the immune system have been commonly used as treatment for inflammatory skin diseases including psoriasis. It has the disadvantage of causing side effects. Therefore, there is a need for research on the development of therapeutic agents for skin inflammatory diseases with high pharmacological effects and low side effects derived from natural products that can compensate for these problems.

Accordingly, the present inventors have completed the present invention in the process of researching a therapeutic agent for allergic inflammation, non-allergic inflammation-related rhinitis, psoriasis, etc. using a natural product-derived material.

Angelica gigas Nakai (Angelica gigas Nakai) is a 2-3-year-old perennial plant belonging to the Asteraceae family. It is a plant known for a long time to have good effects on cold limbs and lower back, menstrual irregularity or menstrual pain, hysteria, menopausal disorders, headache, and anemia. . Recently, decursin, decursinol angelate, and decursinol, which are physiologically active ingredients of Angelica serrata, have analgesic effects, protection against neurotoxicity, dementia prevention, sepsis treatment, antioxidant, etc. It has been reported to be effective.

Qing dynasty ( Polygonum tinctorium ) is an annual herb of the family Knobaceae, also called indigo plant, and the indigo color extracted from the leaves of the blue sage is used as a dye for special fabrics, and is used as an analgesic and antidote. In the blue dynasty, indogo, a representative compound of indigo dye, is isolated, and indirubin is known to have anticancer activity against cancer cell lines.

Korean Patent Application Laid-Open No. 10-2019-0041130, which is a prior art, contains an Angelica gigas extract and deckercin and deckercinol angelate separated therefrom as active ingredients, and includes allergic rhinitis, atopic dermatitis, psoriasis, etc. Although a composition for enhancing immunity for the prophylactic treatment of immune diseases has been described, the synergistic effect of the rhinitis treatment of the Angelica asiatica extract and indirubin of the present invention is not described. Korea Patent Publication No. 10-2017-0133497 discloses that the purified extract containing indirubin can be used for psoriasis, psoriasis, inflammatory skin conditions, etc. The synergistic effect of the treatment of rhinitis has not been described.

In addition, Jeong, HJ, et al. (2014), a non-patent prior literature, describes that polygonum tinctorium extract showed inhibitory effect by applying it to a mouse model of allergic rhinitis. It is different from the present invention using the established and water-insoluble extraction method of indirubin in that it is extracted for a period of time, filtered, and then freeze-dried to make a powder.

Korean Patent Application Laid-Open No. 10-2019-0041130, composition for enhancing immunity comprising fermented Angelica asiatica extract as an active ingredient, published on April 22, 2019. Korean Patent Registration No. 893779, Extraction method of Angelica Quercus extract having the effect of scavenging harmful active oxygen, 2009. 04. 09. Registered. Korean Patent No. 1171434, discovery and improvement of isatin synthase and natural indirubin production method grafted with beta-glucosidase, registered on July 30, 2012. Korean Patent Application Laid-Open No. 10-2017-0133497, extract from Indigo Naturalis and a method for preparing the same, published on Dec. 05, 2017. Korean Patent No. 1728799, a method for manufacturing a homogeneous solubilization solution of poorly soluble active pharmacological ingredients using ethanol and alkaline amino acids, registered on April 14, 2017. Korean Patent No. 1717672, an injection or eye drop formulation formed into a homogeneous solution by solubilizing a poorly soluble active pharmacological ingredient, and a manufacturing method thereof, registered on March 13, 2017. Korean Patent Registration No. 995891, Angelica serrata and Angelica serrata extract using decursin and decurcinol angelate, which have the effect of improving lipid metabolism, as active ingredients, and their extraction method, registered on November 16, 2010. Korean Patent Application Laid-Open No. 10-2019-0142601, an injection or eye drop in which indirubin is solubilized using glacial acetic acid and polyoxy-35-castor oil, and a manufacturing method thereof, published on December 27, 2019.

Kim, K.M., et al., Oral Acute and Subacute Toxicity Studies of Decursin and Decursinol Angelate of Angelica gigas Nakai, Molecular and Cellular Toxicology (2009), 5(2):153-159 Kim, K.M., et al., Absorption, Distribution, Metabolism, and Excretion of Decursin and Decursinol Angelate from Angelica gigas Nakai, J. Microbiol. Biotechnol. (2009), 19(12), 1569-1572 Hwang B.M., et al., Decursin inhibits UVB-induced MMP expression in human dermal fibroblasts via regulation of Nuclear factor-kB, Int. J. Mol. Med (2013), 31(2):477-83 Lee, Y.J., et al., Preventive effect of Angelica gigas Nakai extract oral administration on dry eye syndrome, APJ (2018), 03, 369-375 Kim, K.M., et al., The Preventive Effect of Bacillus polyfermenticus KJS-2 and Angelica gigas Nakai Extract on Triton WR-1339-induced Hyperlipidemia JLS (2018), 8, 101-107 Jeong, H.J., et al., Inhibition of IL-32 and TSLP production through the attenuation of caspase-1 activation in an animal model of allergic rhinitis by Naju Jjok (Polygonum tinctorium), Int. j. Mol. Med. (2014), 33, 142-150 Nickoloff B.J., et al., Injection of Pre-Psoriatic Skin with CD4+ T Cells Induces Psoriasis, The American Journal of Pathology (1999), 155(1), 145-158 Jing Li, et al., Toll-like receptors as therapeutic targets for autoimmune connective tissue diseases, Pharmacology & Therapeutics, (2013), 138(3), 441-451

It is an object of the present invention to provide a composition for treating psoriasis and rhinitis containing an extract of Angelica oleracea and indirubin.

Another object of the present invention is to provide a composition for treating psoriasis and rhinitis, which can maximize the effect of treating rhinitis by mixing the rhododendron extract and indirubin at a certain ratio, comprising the rhododendron extract and indirubin.

The present invention relates to a composition for treating psoriasis or rhinitis comprising an extract of Angelica oleracea and indirubin.

The composition for treating psoriasis or rhinitis is characterized in that the extract of Angelica oleracea contains 70w/w% or more of decursin, decursinol angelate, and decursinol. In addition, the composition for treating psoriasis or rhinitis is a composition for treating psoriasis or rhinitis, characterized in that it comprises 0.01-5 w/v% Angelica asiatica extract and 0.01-5 w/v% indirubin concentrate.

The composition for treating psoriasis or rhinitis is

Anemone extract is

(1) Washing Angelica keiskei, drying the water content below 15 w/v% relative humidity, crushing to 1 mm, and mixing with 50-90% ethanol to obtain a supernatant;

(2) concentrating the supernatant by evaporation to dryness;

(3) dissolving the concentrated extract in 60w/v% ethanol, removing the insoluble portion by filtration, adding the same volume of purified water again, and collecting the precipitate by centrifugation; and

(4) adding hot water to the precipitate, shaking it to settle, discarding the supernatant, and repeating this operation three times to purify the precipitate containing more than 70 w/w% of Decursin, Decursinol angelate, and Decursinol; It is manufactured by a manufacturing method comprising

Indirubin concentrate,

(a) mixing the crushed cheongdae with glacial acetic acid;

(b) filtering the mixture to obtain a filtrate;

(c) adding purified water to the filtrate to precipitate indirubin and centrifuging at 10,000 rpm for 20 minutes to collect the precipitate; and

(d) removing the precipitate by adding ethanol to the precipitate, dissolving it, and centrifuging; It can be prepared by a manufacturing method comprising a.

Hereinafter, the present invention will be described in detail.

The Angelica asiatica extract of the present invention is characterized in that it contains 70w/w% or more of deckercin, decurcinol angelate, and decurcinol. The deckercin, deckercinol angelate, and decurcinol are pyranocoumarin derivatives as physiologically active ingredients of Angelica basilica. Deckersin, deckercinol angelate, and decursinol of the present invention may have a purification rate of 50% or more. Preferably it is 70% or more. The composition for treating psoriasis or rhinitis may include a mixture in which the Angelica oleracea extract and indirubin concentrate are mixed in a weight ratio of 1-5: 1-5, preferably 1-3: 1-3 weight ratio. good. Outside the range of the composition ratio, for example, in the case of a composition ratio of Angelica asiatica extract and indirubin concentrate 1: 6 or 6: 1, the treatment effect for psoriasis or rhinitis may be small, or it may take a long time to relieve symptoms.

The composition for the treatment of psoriasis or rhinitis may include the Angelica asiatica extract, indirubin concentrate, and pharmaceutically acceptable excipients.

The composition for treating psoriasis or rhinitis may be added in an amount of preferably 0.001 to 50% by weight, more preferably 0.001 to 40% by weight, and most preferably 0.01 to 10% by weight based on the total weight of the total pharmaceutical composition.

The pharmaceutical composition may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, liquids, aerosols, etc., external preparations, suppositories, and sterile injection solutions according to conventional methods, respectively. can Carriers, excipients and diluents that may be included in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, it is prepared using commonly used diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, sweeteners, and acidulants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient, for example, starch, calcium carbonate, and water in the solubilized deckercinol of the present invention. It is prepared by mixing cross or lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid formulations for oral use include suspensions, solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweetening agents, fragrances, preservatives, and acidulants are used. may be included. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Non-aqueous solvents and suspending agents include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As the base of the suppository, witepsol, macrogol, tween-61, cacao butter, laurin fat, glycerogelatin, and the like can be used.

When the pharmaceutical composition of the present invention is applied as an external preparation, the external preparation is one type of formulation selected from the group consisting of an ointment, a gel, a cream, a lotion, a liquid, a powder, or a spray. can be manufactured with

The dosage of the pharmaceutical composition of the present invention will vary depending on the age, sex, and weight of the subject to be treated, the specific disease or pathological condition to be treated, the severity of the disease or pathology, the route of administration, and the judgment of the prescriber. Dosage determination based on these factors is within the level of one of ordinary skill in the art, and dosages generally range from 0.01 mg/kg/day to approximately 500 mg/kg/day. A preferred dosage is 0.1 mg/kg/day to 200 mg/kg/day, and a more preferred dosage is 1 mg/kg/day to 200 mg/kg/day. Administration may be administered once a day, or may be administered in several divided doses. The above dosage does not limit the scope of the present invention in any way.

The pharmaceutical composition of the present invention may be administered to mammals such as mice, livestock, and humans by various routes. Any mode of administration can be envisaged, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine or intracerebrovascular injection and dermal application. Since decurcinol of the present invention has almost no toxicity and side effects, it is a drug that can be safely used even when taken for a long period of time for prophylactic purposes.

The present invention is effective for patients with rhinitis by providing a composition for treating rhinitis containing a rhinitis extract and indirubin concentrate, which can maximize the therapeutic effect of rhinitis by mixing an extract and indirubin concentrate in a certain ratio. Not only is it safe, but it can also contribute to the development of a new rhinitis treatment with a low recurrence rate and fewer side effects such as drowsiness, dryness, irritation, nasal burning, and nasal bleeding.

Hereinafter, preferred embodiments of the present invention will be described in detail. However, the present invention is not limited to the embodiments described herein and may be embodied in other forms. Rather, it is provided so that this disclosure will be thorough and complete, and will fully convey the spirit of the invention to those skilled in the art.

<Manufacture of Angelica Root Extract>

According to the Republic of Korea Patent Registration 10-0893779, a purified product of Angelica keiskei was obtained.

Anemone extract is

(1) Washing Angelica keiskei, drying the water content below 15 w/v% relative humidity, crushing to 1 mm, and mixing with 50-90% ethanol to obtain a supernatant;

(2) concentrating the supernatant by evaporation to dryness;

(3) dissolving the concentrated extract in 60w/v% ethanol, removing the insoluble portion by filtration, adding the same volume of purified water again, and collecting the precipitate by centrifugation; and

(4) adding hot water to the precipitate, shaking it to settle, discarding the supernatant, and repeating this operation 3 times to purify the precipitate containing more than 70w/w% of Decursin, Decursinol angelate, and Decursinol; It can be prepared by a manufacturing method comprising a.

Finely pulverize the raw material, chamomile, to 40 mesh or less, dry it to less than 5% moisture content, and add 2 to 4 times the amount of crushed chamomile with medicinal alcohol or alcohol (hereinafter referred to as 'ethanol'). This was sufficiently extracted for more than 12 hours, and this was filtered and concentrated.

1 liter of 95% ethanol per 1 kg of the concentrate was added to dissolve the main component, left at -20°C for 10 hours, and the precipitate was removed by centrifugation to obtain a supernatant, and then the supernatant was evaporated to dryness. After adding 60 v/v% ethanol to the dried product, it was dissolved until completely dissolved. What was not dissolved in 60 v/v% ethanol was removed by centrifugation, and the supernatant was evaporated to dryness. The dried material was dissolved in 95 v/v% or more of ethanol, and the supernatant was taken to obtain an extract of Angelica basilica. As a result of HPLC analysis, it was confirmed that the Angelica persimmon extract contained 90 w/w% or more of decursin, dacurcinol, and decurcinol angelate.

<Production of Indirubin Concentrate>

Take 10 g of blueberry, add 100 ml of ethanol, stir enough to dissolve, and then filter using filter paper to obtain a filtrate. It is known to contain indigo and indirubin in a ratio of about 4:1. These ethanol extracts from Cheongdae contain a large amount of indigo, which has no medicinal effect, so that the medicinal effect is not effective. Therefore, the present inventors performed experiments on various solvents for the purification of indirubin.

As a result of using a number of solvents and extraction methods to isolate structurally similar indirubin from indigo, the present inventors confirmed that indigo did not dissolve in glacial acetic acid, but indirubin was effectively dissolved, as follows. A method for preparing the same indirubin concentrate was established.

Indirubin concentrate,

(a) mixing the crushed cheongdae with glacial acetic acid;

(b) filtering the mixture to obtain a filtrate;

(c) adding purified water to the filtrate to precipitate indirubin and centrifuging at 10,000 rpm for 20 minutes to collect the precipitate; and

(d) removing the precipitate by adding ethanol to the precipitate, dissolving it, and centrifuging; It can be prepared by a manufacturing method comprising a.

A more detailed look at this is as follows.

i) Put 10 g of blueberry in 100 ml of glacial acetic acid and mix thoroughly by stirring. ii) The mixture is filtered using filter paper to obtain a first filtrate. When filtering, Whatman filter No 2 and No 4 were overlapped and used for filtration. iii) 15 ml of glacial acetic acid to the residue was once again dispensed on filter paper to obtain a second filtrate, and after this solution was combined with the first filtrate, 1,000 ml of distilled water was added and centrifuged at 10,000 rpm for 20 minutes to obtain a precipitate . iv) 60 ml of 95% ethanol was added to the precipitate to dissolve, and the precipitate was removed by centrifugation. After taking the supernatant and volatilizing ethanol using a rotary concentrator, an indirubin concentrate was obtained. It was confirmed that the concentrate contained 50 w/w% or more of indirubin as a result of HPLC analysis.

<Preparation of gel formulation containing Angelica basil extract and/or indirubin concentrate>

A gel formulation containing the extract and/or indirubin concentrate obtained above was prepared. In order to solubilize and homogenize poorly soluble pharmacological components, the method of Korean Patent Registration No. 1717672, a prior patent of the present inventors, was used.

600 g of PEG 4,000 and 1400 g of PEG 400 were mixed and dissolved by heating. Lysine HCl 6 g, Tween 80 16 g, Span 4 g, Polyvinylpyrrolidone (K30) 1.6 g in 100 ml purified water was added to the PEG 4,000 and PEG 400 mixture and mixed to adjust the temperature to around 50 ° C., Sorbic acid 4 g was added to prepare a gel composition. Thereafter, the Angelica keis extract and/or the indirubin concentrate obtained above were mixed in the same proportions as in Table 1 below, dissolved in ethanol, put into the gel composition prepared above, mixed uniformly, and cooled to obtain the Angelica basil extract and / Alternatively, a gel formulation containing indirubin concentrate was completed. The control group was prepared by adding the same amount of solvent to the gel composition.

Angelica Root Extract (w/w%) Indirubin Concentrate (w/w%) control 0.0 0.0 Formulation 1 0.0 0.6 Formulation 2 0.1 0.5 Formulation 3 0.2 0.4 Formulation 4 0.3 0.3 Formulation 5 0.4 0.2 Formulation 6 0.5 0.1 Formulation 7 0.6 0.0

<Effect of rhinitis in mouse model of allergic rhinitis of Angelica oleracea extract and/or indirubin concentrate>

The rhinitis effect was confirmed in a mouse model of allergic rhinitis of the Angelica oleracea extract and/or indirubin concentrate obtained above. After maintaining 6-week-old female BALB/c mice (Charles River Laboratories, Inc., Wilmington, Mass., USA) in pathogen-free conditions, 100 μg OVA emulsified in 20 mg aluminum hydroxide (Sigma) was administered intraperitoneally (ip). ) mice were sensitized on days 1, 5 and 14 by injection. Formulations 1 to 7 of the combination in Table 1 were administered intranasally to mice. And one day later, after administration of 1.5 mg OVA to mice, nasal symptoms were evaluated by counting the number of nasal rubs that occurred during 10 minutes.

As a result, formulations 1 to 7 confirmed that the number of nasal rubs decreased compared to the control group, but formulations 2 to 6 significantly reduced the number of nasal rubs compared to formulations 1 and 7, and formulation 4 was the most effective.

<Effect of rhinitis of gel formulation containing Angelica basil extract and/or indirubin concentrate>

From January 2018 to December 2019, a gel formulation with the composition shown in Table 1 was applied to 6 patients with psoriasis and rhinitis at two oriental clinics in Busan and their symptoms were evaluated. As shown in Table 2 below, the rhinitis evaluation stage was divided into 4 stages by combining the number of sneezing, nose blowing, degree of nasal obstruction and degree of disturbance in daily life as shown in Table 2 below, and symptoms other than rhinitis were recorded individually. Each subject had different symptoms and different degrees of rhinitis, so the formulation was applied according to the subject's condition.

type/degree normal rhinitis stage 1 rhinitis stage 2 3 stages of rhinitis 4 stages of rhinitis sneeze
(daily average) 0 1-5 times 6-10 times 11-20 reps 21 or more Nasal juice (number of nose blows per day) 0 1-5 times 6-10 times 11-20 reps 21 or more non-occlusion 0 No mouth breathing but nasal obstruction Sometimes mouth breathing but severe nasal obstruction Mouth breathing for a long time and nasal obstruction is very severe completely blocked all day Interference in daily life 0 no hindrance Between rhinitis stage 1 and rhinitis stage 3 It hurts so much that I can't get my hands on it absolutely impossible

Case 1 (woman in her 30s)

I had stage 2 rhinitis, systemic psoriasis. This person had psoriasis almost everywhere from head to toe, and there were places where the skin became crusty due to drug abuse, and also had severe allergic rhinitis and itching all over the body. As a result of applying the gel formulation containing 0.3w/w% of Angelica persimmon extract and 0.3w/w% of indirubin concentrate, after 90 days, almost all body parts were improved, and the scabs disappeared and there were a few scar-like shapes, and after 12 months was completely healed. However, a slight redness was observed in the inner part of the elbow in the arm, and all other symptoms disappeared.

Case 2 (male in his 50s)

Rhinitis stage 2 patient, 0.3w/w% of rhinitis extract was applied to a male in his 50s living in Busan for 1 week. When the treatment was stopped, it recurred and returned to stage 2 of rhinitis. That is, the 0.3w/w% single preparation of Angelica serrata extract also exerted an effect on rhinitis, but it was difficult to cure or to sustain the effect.

Case 3 (male in his 30s)

A patient with rhinorrhea rhinitis, allergic rhinitis, stage 2 rhinitis, severe nasal congestion when waking up in the morning.

As a result of applying a gel formulation containing 0.3w/w% of Angelica oleracea extract and 0.3w/w% of indirubin concentrate, sneezing disappeared from the first day of application, and rhinorrhea disappeared from the second day, and continued use for 4 weeks (28 days) It was stopped later, and as a result of observation for 2 months, there were no more symptoms. In stage 2 of rhinitis, it was restored to normal.

Case 4 (male in his twenties)

A patient with rhinorrhea rhinitis, allergic rhinitis, stage 3 rhinitis, severe nasal congestion when waking up in the morning, disrupted learning, and expressed pain.

As a result of applying a gel formulation containing 0.3w/w% of Angelica serrata extract and 0.3w/w% of indirubin concentrate, nasal congestion disappeared from the 1st day after 2 hours of application, and rhinorrhea disappeared from the 2nd day, and for 4 weeks ( 28 days), and after observation for 2 months, no more symptoms appeared. It was restored to normal in stage 3 rhinitis.

Case 5 (woman in her 30s)

Nasal rhinitis, allergic rhinitis patient, rhinitis stage 3, severe nasal congestion and sneezing when waking up in the morning.

As a result of applying a gel formulation containing 0.3w/w% of Angelica persimmon extract and 0.3w/w% of indirubin concentrate, nasal congestion disappeared from the first day of application, and rhinorrhea disappeared from the second day, and used after 4 weeks (28 days). was discontinued, and there were no symptoms after 6 months. In stage 3 of rhinitis, it was restored to normal.

Case 6 (Female in her 20s)

Allergic rhinitis, rhinitis stage 1, severe nasal congestion when waking up in the morning.

As a result of applying the gel formulation containing 0.3w/w% of Angelica serrata extract and 0.3w/w% of indirubin concentrate, nasal congestion disappeared from the first day of application, and use was stopped after 4 weeks (28 days), and even after 6 months. There were no symptoms. It was restored to normal in stage 1 rhinitis.

The above cases are shown in Table 3.

case Symptom treatment Treatment time or treatment period result One systemic psoriasis
whole body itch
severe allergic rhinitis Angelica persimmon extract 0.3w/w%
Indirubin Concentrate 0.3w/w% (Formulation 6) 3 months improvement of all body parts 12 months Only the inside of the elbow is red and the rest of the symptoms disappear (cured) 2 rhinitis stage 2 Angelica persimmon extract 0.3w/w% (Formulation 1) 1 week Recover to stage 1 rhinitis
Relapses when treatment is stopped 3 rhinitis rhinitis
allergic rhinitis
rhinitis stage 2
Severe nasal congestion when waking up in the morning Angelica persimmon extract 0.3w/w%
Indirubin Concentrate 0.3w/w% (Formulation 6) 1 day Sneezing gone 2 days

rhinorrhea is gone
discontinue use after 4 weeks;
As a result of observation after 2 months, there was no recurrence (cured) 4 rhinitis rhinitis
allergic rhinitis
3 stages of rhinitis
Severe nasal congestion when waking up in the morning
study guide
show pain Angelica persimmon extract 0.3w/w%
Indirubin Concentrate 0.3w/w% (Formulation 6) 1 day Nasal congestion disappears after 2 hours of application 2 days


rhinorrhea is gone
discontinue use after 4 weeks;
As a result of observation after 2 months, there was no recurrence (cured) 5 rhinitis rhinitis
allergic rhinitis
3 stages of rhinitis
Severe nasal congestion when waking up in the morning
accompanied by sneezing Angelica persimmon extract 0.3w/w%
Indirubin Concentrate 0.3w/w% (Formulation 6) 1 day nasal congestion disappears 2 days


rhinorrhea is gone
discontinue use after 4 weeks;
As a result of observation after 6 months, there was no recurrence (cured) 6 allergic rhinitis
rhinitis stage 1
Severe nasal congestion when waking up in the morning Angelica persimmon extract 0.3w/w%
Indirubin Concentrate 0.3w/w% (Formulation 6) 1 day nasal congestion disappears discontinue use after 4 weeks;
As a result of observation after 6 months, there was no recurrence (cured)

Table 4 below summarizes the medicinal effects and formulation characteristics of single or combined formulations of Angelica asiatica extract and indirubin concentrate through the above case. As shown in Table 4, when used as a single agent, each of the Angelica oleracea extract and indirubin concentrate showed a certain effect in rhinitis and psoriasis, and when used as a combination, clinically superior treatment than when used as a single agent effect was shown.

Formulation effect single agent
(Formulations 1 and 7) - The treatment efficiency is shown.
- 50% cure after 4 weeks of use (recurred within 6 months) Combination formulation
(Formulations 3, 4, 5, 6) - Very good treatment efficiency.
- 80% cure rate after 4 weeks of use (no recurrence within 6 months)

<Formulation Example 1. Pharmaceutical formulation>

Formulation Example 1-1. manufacture of tablets

42.8 mg of Angelica asiatica extract of the present invention and 150 mg of the indirubin concentrate mixture were mixed with 175.9 g of lactose, 180 g of potato starch and 32 g of colloidal silicic acid. After adding a 10% gelatin solution to this mixture, it was ground and passed through a 14 mesh sieve. This was dried, and 160 g of potato starch, 50 g of activity and 5 g of magnesium stearate were added thereto, and the resulting mixture was made into tablets.

Example 1-2. Preparation of injection solution

21.4 mg of the Angelica oleracea extract of the present invention, 75 mg of an indirubin concentrate mixture, 0.6 g of sodium chloride and 0.1 g of ascorbic acid were dissolved in distilled water to make 100 ml. This solution was placed in a bottle and sterilized by heating at 20° C. for 30 minutes.

<Formulation Example 2. Manufacture of health functional food>

Formulation Example 2-1. Manufacturing of health functional food

42.8 mg of Angelica asiatica extract of the present invention and 150 mg of indirubin concentrate mixture, appropriate amount of vitamin mixture, 70 μg of vitamin A acetate, 1.0 mg of vitamin E, 0.13 mg of vitamin B1, 0.15 mg of vitamin B2, 0.5 mg of vitamin B6, 0.2 μg of vitamin B12 , vitamin C 10 mg, biotin 10 μg, nicotinic acid amide 1.7 mg, folic acid 50 μg, calcium pantothenate 0.5 mg, mineral mixture appropriate amount, ferrous sulfate 1.75 mg, zinc oxide 0.82 mg, magnesium carbonate 25.3 mg, potassium monophosphate 15 mg, dibasic calcium phosphate 55 mg, potassium citrate 90 mg, calcium carbonate 100 mg, and magnesium chloride 24.8 mg were mixed to form granules, but it can be prepared by modifying it into various formulations depending on the use. In addition, the composition ratio of the vitamin and mineral mixture may be arbitrarily modified, and it may be prepared by mixing the above ingredients according to a conventional health functional food manufacturing method.

Formulation Example 2-2. Manufacturing of health functional beverages

A beverage was prepared by mixing 42.8 mg of Angelica asiatica extract of the present invention, 150 mg of indirubin concentrate mixture, 0.1 g of citric acid, 100 g of fructooligosaccharide, and 900 g of purified water, followed by stirring, heating, filtration, sterilization, and refrigeration according to a conventional beverage preparation method. .

Claims (8)

A composition for treating psoriasis or rhinitis, comprising an extract of Angelica oleracea and indirubin concentrate. According to claim 1,
The composition for treating psoriasis or rhinitis, the Angelica keis extract contains 70 w/w% or more of deckercin, decurcinol angelate, and decurcinol, and the indirubin concentrate contains 50 w/w% or more of indirubin A composition for treating psoriasis or rhinitis, characterized in that 3. The method of claim 1 or 2,
The composition for treating psoriasis or rhinitis is a composition for treating psoriasis or rhinitis, characterized in that it comprises a mixture of Angelica asiatica extract and indirubin concentrate in a weight ratio of 1-5: 1-5. According to claim 1,
The composition for treating psoriasis or rhinitis has one formulation selected from the group consisting of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories and sterile injection solutions. Or a composition for treating rhinitis. 5. The method of claim 4,
The topical agent is for the treatment of psoriasis or rhinitis, characterized in that it has one formulation selected from the group consisting of ointments, gels, creams, lotions, liquids, powders or sprays. composition. 3. The method of claim 1 or 2,
The rhinitis is allergic rhinitis, infectious rhinitis, hypersensitivity non-infectious rhinitis, irritant rhinitis, atrophic rhinitis or specific granulomatous rhinitis, psoriasis or rhinitis treatment composition. According to claim 1,
The rhinitis is a composition for treating psoriasis or rhinitis, characterized in that it is rhinitis accompanied by atopic dermatitis. According to claim 1,
Anemone extract is
(1) washing, drying, crushing, and mixing with 50-90% ethanol to obtain a supernatant;
(2) concentrating the supernatant by evaporation to dryness;
(3) dissolving the concentrated extract in 95 w/v% ethanol, removing the insoluble portion by filtration, adding the same volume of purified water again, and collecting the precipitate by centrifugation; and
(4) adding hot water to the precipitate, shaking it to settle, discarding the supernatant, and repeating this operation three times to purify deckercinol, deckercinol angelate, and deckercinol containing 70w/w% or more; containing; Manufactured by a manufacturing method,
Indirubin concentrate,
(a) mixing the pulverized blueberries with glacial acetic acid;
(b) filtering the mixture to obtain a filtrate;
(c) adding purified water to the filtrate to precipitate indirubin and centrifuging at 10,000 rpm for 20 minutes to collect the precipitate; and
(d) dissolving by adding ethanol to the precipitate and centrifuging to remove the precipitate; psoriasis or rhinitis treatment composition comprising a.