KR100354608B1 - Pharmaceutical compositions for preventing and treating allergic diseases and methods for preparation thereof - Google Patents

Abstract

The present invention as an active ingredient Gilgyeong, golden, Jisil, hyeonggae, Shiho, white paper, Earl, Cheongung, Dongguk, windproof, Yeongwa, licorice, gold silver flower, pogongyeong, cheonhwabun, Yugeunbaekpi, Hwanggi, Baekchul, Saengjihwang, Cheoncho, Xinhua, Changja It relates to a pharmaceutical composition for preventing and treating allergic diseases, including baekhyeolpi, halved, horseback riding, rooting, and peppermint, and a method of manufacturing the same.

Description

Pharmaceutical compositions for preventing and treating allergic diseases and methods for preparation

The present invention relates to a pharmaceutical composition for the prevention and treatment of allergic diseases and a method of manufacturing the same. More specifically, the present invention as an active ingredient Gilgil, golden, jisil, hyeonggae, shiho, white paper, earl, cheongung, donkey, windproof, yeonkyo, licorice, gold and silver, pogongyoung, cheonhwabun, yugeunbaekpi, Astragalus, baekchul, saengjihwang, cheoncho, Acute and chronic allergic rhinitis (including chronic sinusitis), allergic dermatitis, including allergic otitis media (including recurrent otitis media), allergic conjunctivitis, It relates to a pharmaceutical composition for the prevention and treatment of allergic asthma and the like and a method of manufacturing the same.

The normal immune response stimulates the effect molecules to eliminate the attack of allergens by various mechanisms to remove foreign substances or cause local inflammation without damaging the host tissue. However, depending on the condition, the term hypersensitivity or allergy is used when the immune response is excessively increased or the reaction proceeds to an unwanted reaction. Allergic diseases are more severe where civilization develops and require more medical expenses. According to Scientific American, September 1993, more than 20% of the US population suffers from allergic symptoms, with allergic rhinitis being the most common. Occasionally, the allergen attack was fatal, and asthma alone cost $ 3.6 billion in direct health care in the US, according to 1990 statistics. In Korea, the number of patients suffering from these allergic diseases is at the level of developed countries, and is increasing every year. In particular, the number of pediatric patients is increasing rapidly. Therefore, many researchers are working hard to develop causative therapies to alleviate the economic, physiological and psychological burdens caused by these allergic diseases.

Diversification and complexity of allergic diseases can be attributed to the fact that modern life is exposed to various allergens. Synthetic fibers such as nylon and teflon, which have revolutionized the apparel industry, and synthetic resin products such as polyethylene, polyester, and epoxy resin, which have been settled in our daily lives, work with various chemical substances such as monomers and polymers. This causes anaphylactic contact dermatitis on the skin or mucous membranes. On the other hand, contact with eyeglass frames, dentures, wristbands, plastic umbrellas, and sunshade handles not only causes allergic inflammation on the skin, but also polyurethane, which is widely used as paint for automobiles, furniture, musical instruments, etc. It is the main cause of asthma. Metals such as platinum, gold, mercury, and nickel, as well as rubber, leather, and cement also cause allergic contact dermatitis. Accessories, jewelry, or rubber products such as earrings, necklaces, and rings are also a problem. It is well known that food allergies are caused by additives such as instant foods, preservatives, artificial sweeteners and food coloring.

Since the drug used as the root bark has been introduced into the synthetic era, drug shocks, including antibiotics shock, chemical allergy such as sulfa agent, salicylic acid agent, pyrazolone agent, and local anesthetic agent, and enzymes are being followed. It has also been found that the mechanism of development of food and drug allergies occurs in all types of hypersensitivity reactions I, II, III and IV. Cosmetic allergies have also occurred frequently, and pollution caused by environmental pollution causes or worsens allergic diseases of the respiratory tract, and bronchial asthma is rapidly increasing. Occupational allergies are also attracting attention these days. Bakery asthma, dandruff asthma, librarian's asthma, carpenter's wood asthma, poultry asthma, welder's contact dermatitis, and many more.

Allergic reactions begin with the production of IgE antibodies that bind strongly to receptors on mast cells or basophils. Antigens (allergens) phagocytosed by antigen-providing cells, such as macrophages, are processed and then the peptides are presented by MHC class II molecules on the cell membrane surface and recognized by receptors on the T cell surface (TCR). In activated T cells, IL-2, IFN-γ, tumor necrosis factor (TNF) -β (these are released from Th1 cells) and IL-4, IL-5, IL-6, IL-9, Cytokines are produced, such as IL-10 (they are liberated in Th2 cells). The resulting cell activators act on T and B cells and are involved in their division and proliferation. Next, B cells are activated by binding of CD40 ligand (CD40L) on T cells and CD40 on B cells. Moreover, when IL-4 released from T cells is added, B cells differentiate into IgE producing cells by class switch. do. In mast cells, a series of biochemical processes occur in which two molecules of IgE antibodies bind to multivalent antigens, forming crosslinks on cell membrane receptors, resulting in degranulation. In mast cells, degranulation releases various chemical mediators, such as histamine, resulting in capillary permeability, smooth muscle contraction, and mucus secretion along with prostaglandins and rucotrienes, which are newly produced by arachidonic acid metabolism of cell membranes. It occurs momentarily, and the skin develops pruritus, redness, gallbladder, and vascular edema, relieves in the respiratory tract, suffocation, chest compressions, dyspnea, cyanosis, paleness in the cardiovascular system, hypotension, arrhythmia, etc. Symptoms such as vomiting, hari, and nervous system are accompanied by symptoms such as paresthesia, dizziness, headache, cramps, consciousness disorders.

As an allergic disease, sinusitis, a chronic sinusitis that is common in allergic constitutions, is a case where the epithelium of the paranasal sinuses causes irreversible changes such as detachment, degeneration and vascular coagulation due to repeated acute sinusitis. A polyp develops into it. Such chronic sinusitis does not respond well to medical treatments such as antibiotics, and surgical treatment is not suitable for children with sinus development, and in adults, there is no underlying treatment for colds through immune boosting even after surgery. As long as it recurs.

In addition, otitis media is a common disease with a 70% chance of being infected more than once in childhood, and despite treatment with antibiotics, 10% of acute otitis media become chronic. Especially in children with weak immunity, recurrent exudative otitis media, which is caused by exposure to upper respiratory tract infection before chronic otitis media is cured, is prolonged, causing prolonged hearing loss, severe adhesions of the tympanic membrane and bone tissue destruction. Repeated viral and secondary bacterial infections caused by chronic sinusitis and adenoid hypertrophy and bile duct obstruction are combined with recurrent exudative otitis media due to chronic sinusitis and adenoid obstruction. .

In alleviating such various allergic symptoms, the effects of the drugs currently being used are solid, and side effects due to prolonged administration are problematic. Antibiotics do not affect the inhibition of IL-6, which plays an important role in the pathogenesis of chronic mucinous exudation in children, and has been reported to be inhibited by antibiotics and steroids. Prolonged use of steroids has the side effect of lowering immune system function. In addition, there is a problem that the economic and psychological burden of the patient is great.

Therefore, the present inventors continued clinical research and experiments by focusing on the treatment of chemo-negatives (도와 正 도와), which helps to prevent and treat various allergic diseases without side effects in a fundamental way, and to help prevent the body's immunity, regularity. By properly combining the specific herbal medicines, it was confirmed that excellent medicinal effects with almost no conventional problems as described above were completed and the present invention was completed. In particular, the composition of the present invention can increase the immunity of the child, not only to treat the inflammation of the paranasal sinus, but also to suppress allergies, and to minimize the occurrence of colds.

The present invention as an active ingredient Gilgyeong, golden, Jisil, hyeonggae, Shiho, white paper, Earl, Cheongung, Dongguk, windproof, Yeongwa, licorice, gold silver flower, pogongyeong, cheonhwabun, Yugeunbaekpi, Hwanggi, Baekchul, Saengjihwang, Cheoncho, Xinhua, Changja It relates to a pharmaceutical composition for preventing and treating allergic diseases, including, baekhyeolpi, half, horse riding, rooting, and peppermint. In addition, the composition of the present invention preferably further comprises at least one member selected from the group consisting of creation, dermis, cause of death, nutmeg, ume, sessin, neck, moth, and right ear.

Gilkyung used in the raw material herbal medicine in the present invention is the expectoration of the tobacco, crown boss; Gold has anti-inflammatory, antipyretic, analgesic, antibacterial, anti-hypersensitive, antiviral effects; The fruiting is a halo, antiallergic action; The hounds have anti-inflammatory, slowing, antimicrobial efficacy in the throat. Shiho announces Fever, Jinkyung, Pain Relief, Fever, Jinhae. Has anti-inflammatory action; White paper has the effects of tonggyu beef, sojong, and paper pain; Earl has a calming, cramping, antipyretic, analgesic, antibacterial, anti-inflammatory, vasodilating effect; The uterus has the effect of sedation, hemostasis; Angelica has blood, lubrication, soothing, analgesic, antibacterial activity; Windbreaks are effective in clearing, analgesic, anti-pathogenic microorganisms, anti-inflammatory; Ducts have the effect of clearing, anti-inflammatory, drainage, pain, vitality, and swelling; Licorice has antitussive, expectorant, detoxifying, alveolar, anti-inflammatory, analgesic and anti-hypersensitive effects; Gold and silver coins are effective in clearing, detoxifying, winning, and activating blood; Pogongyoung has the effect of clearing detoxification, soon-san, antibacterial, antiviral, antifungal, diuretic; Natural flower has vibrancy, fertilization, seedling, drainage effect; Radical white skin has the effect of small number, detoxification fever, anti-inflammatory; Astragalus has boil, turbid poison, drainage, painful action; Baekchul has the effect of Bobby ripening, humidity control, high labeling; Saenghwanghwang is effective in clearing, bleeding, and vibrancy; Cheoncho has a moderate to moderate action; Shin Yi Hwa and Chang Chang have the efficacy of sensational tonggyu beef; Morus bark has the efficacy of pneumonia, Pseudomonas spp .; There is a counteracting hum expectancy; Horseback riding has the effect of deciphering; Brown root has the effect of vitality, peppermint has a dissipative wind fever, and a scaly throat.

In addition, the creation of the composition of the present invention may further include the action of dryness, humidity; The dermis has the effect of ecchymoses, carcass sputum, and Jeongcheonjinhae; The cause of death is the mid-planet, the Onvi Governor; Nutmeg is effective in warming periods and indels; Buckwheat has the effect of dysfunction, intubation, viability; Sessin has the effect of warming walls, radiating and painful; The neck is effective for breathing, strengthening the mucus; Nachos have the effect of hangang news and gangdam; Uiin is known as a drug that has the efficacy of blue heat drainage, dihydrogen species, dry skin, anti-inflammatory.

The composition of the present invention is preferably Gilyeong, golden, fruit, hyunggae, shiho, white paper, white pear, cheonggung, donkey, windproof, duct bridge, licorice, gold silver flower, pogongyoung, cheonhwabun, yugeunbaekpi, hwanggi, baekchul, saengjihwang, cheoncho, xinhua , Changi, baekhyeol, halves, horseback riding, rooting, peppermint 4-6: 2-4: 3: 3: 3: 3: 3: 4-6: 4: 4-8: 2: 2-6: 4-8: 6 -12: 8-12: 4: 6-12: 6-10: 4-8: 4-8: 2: 2-4: 4-6: 4-6: 4: 2-4: 4-8: 2 It is included by the weight ratio of.

In addition, the composition of the present invention has a weight ratio of 4: 4: 4: 4: 2-4: 2: 3: 4: 8-10, creation, dermis, sign, nutmeg, plum, sessin, neck, moth, and right ear It may further comprise one or more selected from the group consisting of.

The composition ratio of the herbal medicines is obtained based on the results of many clinical trials and animal experiments, and if it is lower than the lower limit, the pharmacological effect of the ingredient is rapidly decreased, and if it is higher than the upper limit, the synergistic effect is lowered. And the cooperativeness of the composition is significantly degraded.

The composition of the present invention can be used as a prophylactic and therapeutic agent for allergic diseases such as acute and chronic allergic rhinitis (including chronic sinusitis), allergic dermatitis, allergic otitis media (including recurrent exudative otitis media), allergic conjunctivitis and allergic asthma. These pharmacological effects can be confirmed from Experimental Examples 1 to 4. The mechanism of pharmacological action of the composition of the present invention cannot be accurately demonstrated, but it is assumed to suppress local and systemic allergic reactions due to the regulation of production of cell activators and chemical mediators from immune cells.

The pharmaceutical composition of the present invention may be prepared by mixing the above herbal medicines, or extracting the herbal medicines according to the physicochemical properties of the medicinal medicinal ingredients with a solvent or by concentrating and drying the powder obtained by mixing them with a pharmaceutically acceptable carrier. Phosphorus pharmaceutical preparation method can be used to prepare pills, granules, sprays, liquid formulations and the like. The composition of the present invention is preferably in the form of liquid, but if necessary, it may be prepared in the form of pills, granules, sprays, suppositories, tablets or capsules, and may be used in other dosage forms when necessary.

The pharmaceutical composition of the present invention is, for example, 4-6g Gilgil, 2-4g golden, 3g gyeonghyeong, 3g hyeonggi, 3g shiho, 3g white paper, 4-6g Baekgi, 4g gunggi, 4g 8g, windproof 2g, Yeongyo 2 -6g, licorice 4-8g, gold and silver coins 6-12g, pogongyoung 8-12g, cheonhwa flour 4g, rooted radish 6-12g, Astragalus 6-10g, Baekchul 4-8g, raw green sulfur 4-8g, Cheoncho 2g, Xinhua 2-4g, Changiza 4-6g, lettuce 4-4g, halved 4g, horse riding 2-4g, brown root 4-8g, peppermint 2g, and randomly produced 4g, dermis 4g, sine 4g, nutmeg 4g, ume 2-4g, sesame 2g, neck 3g Pour 1000ml of water into a mixture of 4g moth, 8-10g of Euphorbia, concentrate for about 1 hour and a half, and concentrate to about 150ml. A typical single dose is 1.5-2 ml / kg body weight, which is taken three times a day. For example, if a child weighs 20 kg, take 30 ml-40 ml three times a day. However, the composition of the present invention can be appropriately increased or decreased the dose depending on the weight, age, sex, severity of the condition and digestion status. In other formulations, appropriate amounts may be administered orally or parenterally.

Take 3 months for chronic allergic disease, 4 months for chronic sinusitis, 3 months for allergic recurrent otitis media, and 5 months for atopic dermatitis.

Hereinafter, the present invention will be described in more detail with reference to Examples, but this does not limit the scope of the present invention.

Example 1 Preparation of Liquid

Gilgyeong 5g, golden 3g, fruit 3g, hyunggae 3g, shiho 3g, white paper 3g, earl 5g, cheonggung 4g, donkey 6g, windproof 2g, duct bridge 4g, licorice 6g, gold silver flower 9g, pogongyoung 10g, cheonhwahwa 4g, Yugeunbaekpi 9g, Huanggi Pour 1000ml of water into a mixture of 8g, white ginseng 6g, raw sulfuric acid 6g, cheonchocho 2g, xinhua 3g, changja 5g, lettuce white pepper 5g, halved 4g, horse riding 3g, brown root 6g, peppermint 2g, about 1.5 hours, concentrated to about 150ml To make liquid.

Example 2 Preparation of Liquid

Gilgyeong 5g, golden 3g, fruit 3g, hyunggae 3g, shiho 3g, white paper 3g, earl 5g, cheonggung 4g, donkey 6g, windproof 2g, duct bridge 4g, licorice 6g, gold silver flower 9g, pogongyoung 10g, cheonhwahwa 4g, Yugeunbaekpi 9g, Huanggi 8g, white ginseng 6g, raw yogurt 6g, Cheoncho 2g, xinhua 3g, changja 5g, baekbaek 5g, halved 4g, horse riding 3g, brown root 6g, peppermint 2g, and creation 4g, dermis 4g, signature 4g, nutmeg 4g, omega 3g, sesame 2g Into a mixture of 3g, 3g of neck, 4g of moths, 8g of Uiyi, 1000ml of water was poured into the mixture for about 1.5 hours and concentrated to about 150ml.

Example 3: Preparation of Other Formulations

According to a common method generally known, pills, granules, sprays, tablets, and capsules were prepared from the extracts.

Experimental Example 1: Toxicity and Side Effects Confirmation Test

1 times (2 ml / kg), 5 times (10 ml / kg), 10 times the dose ratio (ie, the dosage of 1.5-2 ml per kg of body weight) to administer the liquid preparation prepared in Example 2 (20 mL / kg) dose was administered orally to 30 adult rats for 90 days and observed daily for more than 30 days. As a result, no apparent physiological abnormalities or any anatomical findings were found in all experimental groups.

The present inventors studied the appropriate dosage and administration method for hundreds of patients from 3 years old to adult, male and female, and as a result, after determining the standard dosage, the subject's age was increased or decreased. To be administered. In the few cases, no local or systemic side effects were identified except gastrointestinal discomfort and transient phenomena. The gastrointestinal discomfort was eliminated after the dose was reduced to 1/2 to 2/3.

Experimental Example 2: Clinical Effect Experiment on Allergic Disease

This clinical trial was conducted in the pediatrics of Jeonju Oriental Hospital of Jeonju-si, Jeonju-si, and the Department of Otorhinolaryngology of Wonkwang University-affiliated Hospital, Iksan, Korea. The administration of the solution of the present invention was carried out. Most patients were 3-15 years old and allergic disease ranged from 1 month to 96 months. These patients can be classified as a temporary allergic disease of 120 patients or 380 chronic recurrent allergic diseases.Allergic rhinitis and chronic recurrent sinusitis sinusitis, recurrent exudative otitis media, atopic dermatitis, chronic urticaria, bronchial asthma In some cases, the disease appeared alone, but in most cases, several species were expressed together. There was no abnormality in the general medical examination, but the iris constitution was divided into weak constitution, weak constitution, weak constitution, and weak kidney. Deformed group, 35 cases of respiratory allergy and 35 gastrointestinal allergy by MAST test showed positive antigen and increased IgE levels, CT and sinus mucosa on computed tomography (CT) Were classified into the group with thickening of the endometrium, or the group with thickening of the inferior nasal concha in the endoscopy, and the group with the retention of the intracranial bleeding in the middle ear. The main cause of the disease was imbalance of the bioimmune system, and particularly, hypersensitivity reactions to antigens and various viruses were caused by imbalance between the gastrointestinal stomach, the respiratory lung, and the urinary blood and yang of the genitourinary system. Most of these patients were overdose with antibiotics and steroids for more than one to three years as a bilateral treatment, and antiallergic drugs such as general antihistamines had no effect except for temporary symptoms.

This solution was taken 3 times a day, 2ml / 1kg at a time, and then the progress was observed every 10 days. The efficacy evaluation of the composition of the present invention evaluated the improvement of symptoms through aberration follow-up at 10 days intervals and endoscopy once a week, simple imaging or CT once every two months, blood count once The test was performed at 2 months to evaluate the progress of treatment.

A total of 110 children with sinusitis, chronic recurrent sinusitis, who were allergic to allergy, had a 90-day treatment rate on x-ray and CT, with 10% unchanged.

About 85% of all 100 patients with allergic rhinitis improved their symptoms such as sneezing, runny nose, nasal congestion, itching of nasal mucosa, congestion and pruritus of conjunctiva, and decreased edema and secretion of nasal endoscopy. About 10% did not, and about 5% did not follow long-term follow-up.

About 80 children aged 2-13 years with frequent recurrent otitis media in children with allergic predispositions showed sinus tomography and computed tomography in approximately 42% of children with chronic sinusitis. 2 Tomography and computed tomography (CT) were performed every month, and the mucosal thickening of the paranasal sinuses was reduced, resulting in a decrease and disappearance of the middle ear effusion at the time of diagnosis. It was confirmed that otitis media was treated. Otitis media has been treated, but if the mucous membrane thickening of the sinuses is not completely cured, it can be recurred by cold, so tomography or computed tomography (CT) was performed every two months. Children with recurrent otitis media with chronic sinusitis were treated for not only otitis media, but also sinusitis, a mucosal thickening of chronic sinuses.

Two-year-old adults with atopic dermatitis showed improvement and treatment of 80% of symptoms with 3-6 months of treatment, but 10% had no change and 10% had no long-term follow-up. It was.

Bronchial asthma was more commonly referred to as bronchial asthma (sinubronchitis) and was associated with bronchial asthma and chronic recurrent sinusitis. In bronchial sinusitis, a bronchial asthma with chronic recurrent sinusitis, children aged 2 to 15 years showed improvement or treatment of 82% with 2-6 months of treatment, 8% with no change, and 10% with long term Failed to follow up.

Experimental Example 3: Tomography and computed tomography test for the treatment effect of sinusitis, a frequent chronic recurrent sinusitis in allergic constitution

Simple radiographs have false positive rates of false positives and are difficult to differentiate accurately and chronically from sinusitis, and there are no studies on the treatment of chronic sinusitis using CT at home and abroad.

Therefore, the present inventors have been diagnosed as having sinusitis in patients with severe sinusitis and the incidence and recurrence of chronic sinusitis among patients with sinusitis visited to Jeonju Oriental Medicine Hospital of Wonkwang University Hospital. Chronic sinusitis using tomography and computed tomography (CT) Was diagnosed and confirmed that the thickening of the mucosa and the clinical symptoms were treated in the composition of the present invention prepared in Example 2.

(1) object

Simple radiography was performed to target the first 998 years of the two patients who visited a week Wonkwang University Oriental Hospital from January to March 1999, 48 patients with unleaded. Of the 48 patients, 24 were female and 24 were male. The age ranged from 3 to 13 years, with an average age of 6.4 years. The medical history ranged from 10 to 48 months with an average medical history of 10.6 months. The mean duration of treatment was 11 months at 3 months. Thirty patients (63%) had allergic diseases within their uncle's family history, and 31 children had respiratory allergies such as otitis media, allergic rhinitis, capillary bronchitis, and asthma, and digestive allergies such as milk allergy and irritable colitis. 65%).

Computed tomography was performed in 42 patients with chronic sinusitis who visited Wonkwang University Jeonju Oriental Hospital for 9 months from December 1998 to August 1999. Of the 42 patients, 21 were women and 21 were men. The age ranged from 4 to 13 years with a mean age of 6.7 years. The medical history ranged from 10 to 96 months with an average of 14.2 months. The duration of treatment ranged from 28 to 200 days. It was 96 days. Thirty-two cases (76%) were allergic due to family history. Respiratory allergies such as otitis media, allergic rhinitis, capillary bronchitis and asthma, digestive allergies such as milk allergy and irritable colitis, and atopic dermatitis and ulcers 37 children (88%) had skin allergies.

(2) Change of photograph before and after treatment

Simple radiographs were taken of Water's view to examine bilateral maxillary sinus, ethmoid sinus and frontal sinus. In the past, otitis media, allergic rhinitis, skin allergies, capillary bronchitis, asthma, respiratory allergies such as asthma, milk allergies and irritable colitis such as allergic groups, and allergic groups, and divided into non-allergic groups, the degree of radiation shadow and sinus thickening of the sinuses is normal The treatment period was divided into four stages: mild, severe, and severe. Normal is when the shade of the sinuses is the same as oral or nasal or no obvious difference (0 points), mild is thickening of the mucous membrane or bone thickening, but overall increase in shadow (1 point) Symptoms of the mucous membrane are clearly visible but limited to only part of the sinuses and no bone thickening (2 points). Case (3 points) and statistical analysis was performed using the Wilcoxon Signed Ranks Test to organize discontinuously scores.

In computed tomography, three images of axial and coronal planes were obtained at 2 cm intervals, centering on the maxillary sinus and ethmoid sinus. Therefore, neither the frontal sinus nor the sphenoid sinus was examined, and some of the pictures taken at an external hospital included the frontal sinus and the sphenoid sinus. Computed tomography analysis of the sinuses divided the pre- and post-treatment into four stages: normal, mild, moderate, and severe, focusing on the thickness of the mucosa and the thickening of the bone. If the thickness of the sinus mucosa is 3 mm or less and there is no bone thickening (0 point), the mild case is 3-5 mm thick and there is no bone thickening (1 point). If the thickness is 5mm-1cm and there is no thickening of the bone (2 points), the severity is divided into the cases where the thickness of the mucosa is more than 1cm and accompanied by the thickening of the bone (3 points), using the Wilcoxon Sine Rank Test. The treatment period was divided according to the presence or absence of allergy, and both cases of sinusitis were classified as severe cases.

(3) improvement of symptoms

We investigated the symptoms before and after the treatment of chronic sinusitis in children. Simple radiography subjects were retrospectively reviewed (ie, examining the past history, family history, address, and current symptoms of patients who had previously reported to the care department). Patients who underwent computerized tomography were prospectively (ie The patient's past history, family history, address, and current symptoms were investigated.

(4) Therapeutic Effect of Sinusitis by Simple Radiographic Diagnosis

When comparing the pre-treatment picture with the picture taken after the symptoms disappeared, 46 (96%) were treated in the picture, 2 (4%) were unchanged, and there was no deterioration. Inflammation frequency was most common in the maxillary sinus (100%), followed by ethmoid sinus (50%), maxillary sinus (17%), and the remaining sinus sinus (12%) after treatment. The most common was maxillary sinus (4%) and frontal sinus (2%).

The duration of the 46 patients treated on the radiographs took 89.3 days. 28 patients with thickening of the maxillary sinus mucosa were 93 days long, 15 patients with severe mild thickening were 68 days, and 3 patients with mild thickening took 75.5 days. The 23 patients with maxillary sinus inflammation, including the ethmoid sinus, took 87.3 days, and 25 patients with only the maxillary sinus were inflamed and the sinus sinus did not have 76.5 days. On average, 30 patients with bilateral maxillary sinus inflammation took 84.3 days, 8 patients with right maxillary sinus inflammation were 61.6 days, and 8 patients with left maxillary sinus inflammation were 63.6 days. It was longer.

Before treatment, thickening of maxillary sinus mucosa was 30 severe, 15 severe and 3 mild, but not normal. After treatment, 2 severe, 2 severe, 26 mild and 18 normal. There were statistically significant results (P <0.005) when statistical treatment was made with 0 points for normal, 1 point for mild, 2 points for mild to severe, and 3 points for severe.

(5) Therapeutic Effect of Sinusitis by Computerized Tomography Diagnosis

In comparison with pre-treatment and post-treatment photos, 38 patients (90%) were treated and 2 patients (5%) were unchanged. The case where there was no change was included in the case where there was no change. The average duration of treatment for 38 patients was 93.7 days. Of the 35 treated, 29 had severe thickening of the mucosa and 104.9 days, and 9 had severe thickening of the mucosa and 73 days. Inflammation of ethmoid sinus sinus sinus sinus sinus sinus sinus sinus sinus sinus sinus 28 patients with bilateral maxillary sinus inflammation took 98.5 days, 6 patients with right inflammation had 76.7 days, and 4 patients with left infection had 58 days of treatment. Treatment lasted longer than 30 days.

Two patients (5%) developed more thickening of mucosa after treatment than before treatment.

Before treatment, the maxillary sinus mucosa was thickened in 30 patients, moderate in mild to moderate in 2, and mild in 2, and there was no normal. After treatment, 6 patients in severe, 6 in mild and 30 in normal. There were statistically significant scores (P <0.005) when scores of 0 for normal, 1 for mild, 2 for severe and 3 for severe were significant.

(6) Therapeutic effect of allergy

On radiography, the average duration of treatment for allergy patients was 84.6 days, and for 17 patients without history of allergy, 98.5 days, the duration of treatment for patients without allergies was longer, and the two untreated patients had history of allergy. .

On the other hand, in CT, the mean duration of treatment of allergy in 37 patients was 110.8 days, and in 5 patients without allergy, the duration of treatment was shorter (40.6 days), and all untreated patients had allergies.

(7) symptom improvement rate

For 48 patients with simple radiography, the most common symptoms were coughing in the morning or in the evening (63%), coloration (63%), nasal swelling (54%), and persistent posterior rashes (後 鼻 漏). Irritated throat with swollen throat (52%), nasal congestion (48%), nosebleed (24%), headache (17%), open mouth and breathing (12%) %), Snoring (6%), and 42 patients with computed tomography had the most coloration (83%), nasal swelling (71%), morning cough or evening cough (69%), and persistent postnasal fistula. The irritated throat was swollen (57%), nasal congestion (50%), snoring (38%), headache (31%), and nosebleed (19%).

The symptom of 90 patients had the most coloration (72%), seawater (69%), nasal swelling (62%), and chronic lymphocytic lymphoma of the throat with chronic posterior swelling (54%). ), Fubiru (49%), open mouth (28%) and headache (23%).

After 1-2 months of treatment, 60% had improved symptoms, and 2-4 months of treatment showed more than 90% of symptoms, and 10% of patients showed no change.

(8) frequency of prescription use

The composition of the present invention (81%) was used if the patient had a sinusitis, and the composition of the present invention (77%) was also used for the CT patient. The composition of the invention was also used predominantly (81%) for 90 patients.

(9) Conclusion

Through the composition of the present invention prepared in Example 2 clinical symptoms were recovered only 95% or more clinical symptoms were recovered, it was confirmed that the therapeutic effect showed improvement in the picture. Treatment of chronic sinusitis through herbal remedies increases the body's immunity, treats mucosal thickening and allergies, improves resistance to colds, and reduces the morbidity. This is because chronic sinusitis has a high recurrence rate and is reported to recur if the cold persists for more than two weeks or if proper treatment is not performed even after medical or surgical treatment.

Among 90 patients with clinically chronic sinusitis, 38 patients underwent computed tomography showing chronic thickening of the mucous membrane and chronic radiography without air-fluid level, acute sinusitis. Forty-six were treated, and the compositions of the present invention were effective in treating chronic sinusitis by increasing systemic immunity, suppressing allergy, restoring thickened mucosa to normal.

Experimental Example 4 Analysis of Cellular Active Substances in Middle Ear Solution

Recently, the importance and interest of immunological mechanisms are increasing as a cause of otitis media. In particular, cytokines are mediators of inflammation and immune responses, as well as host defense during bacterial infection or inflammation, as well as tissue destruction. Interleukin (IL) -1 is highly measured early in exudative otitis media, and IL-6 is involved in the production of specific antibodies in immune cells to remove bacteria or free substances from the middle ear cavity. TNF-α is measured as the duration of morbidity is high, and it is found that these cytoactive substances are involved in the pathogenesis of various diseases and drugs that control them have potential as therapeutic agents.

In this regard, the present inventors quantified IL-I, IL-2, IL-6 and TNF-α, which are cytoactive substances in effusions isolated from the middle ear cavity of children who received antibiotics among otitis media patients and children who took the composition of the present invention. The effect of Chinese medicine treatment on otitis media on cell activator in middle ear canal was obtained.

(1) object

Among 24 patients of 17 patients diagnosed with recurrent exudative otitis media from September 1997 to May 1999 at the Department of Otolaryngology at Wonkwang University Hospital, antibiotics (Augmentin syrup, Cefzil for 2-6 months) ) 13 ears (antibiotic group) of 10 people who were treated syrup, Lorabid syrup alternately at weekly interval) and 7 who took the composition of the present invention for 1-7 months at Jeonju Oriental Hospital of Wonkwang University The middle ear reservoirs collected from the eardrum perforation or the ventilator tube in 11 ears (Herbal group) were used. The specimens were divided into serous (11 ears) and mucous (13 ears) according to the gross appearance, and the age distribution was 3 ears in 5 years old group, 18 ears in 6-10 years old group and 3 ears after 11 years old after birth. It was. The duration of disease was divided into the period from onset to surgery, and divided into two groups: Chinese medicine group (11 ears) and antibiotics group (13 ears). Eight ears had a history of tympanostomy or ventilator insertion, and 16 ears had no history.

(2) Collection of middle ear reservoir

Middle ear effusions were collected aseptically after tympanic dissection in the group to which antibiotics were administered (13 ears) and the group to which the composition of the present invention was administered (11 ears). The effluent was separated and centrifuged at 2000 rpm for 10 minutes by adding PBS buffer solution. The separated supernatant was lyophilized, dissolved in the same volume of PBS buffer solution, and stored at -70 ° C for quantification.

(3) Quantification of Cellular Active Materials

Cell activators were quantified by ELISA (Enzyme-linked immunosorbent assay) method, ELISA was performed in duplicate in 96 well ELISA plate. 1 μg / ml of the monoclonal antibody for each cell activator was diluted with PBS (pH 7.4), coated in 100 μl each in a 96 well plate, and then left at 4 ° C. for 12 hours. The plate was washed with PBS containing 0.05% Tween and then blocked for 1 hour with PBS containing 1% BSA, 5% sucrose, 0.05% NaN ₃ . After a few washes, the exudates isolated from the ear of otitis media patients were lyophilized and added to PBS-dissolved samples or standard cell activators and left at 37 ° C for 2 hours. After standing at 37 ° C. for 2 hours, each well was washed again, and 0.2 μg / ml of biotin-bound antibody was added thereto, and the mixture was further left at 37 ° C. for 2 hours. The wells were washed off and then avidin peroxidase was added and left at 37 ° C. for 20 minutes. The wells were washed again and then ABTS substrate was added, and the color reaction was measured at 405 nm using an ELISA reader. The total protein of the middle ear reservoir was measured by the BCA method.

(4) analysis

Due to the high viscosity of the middle ear reservoir solution, it is difficult to measure the concentration and capacity. After adding the buffer solution to all the middle ear reservoir solutions, the cell active material and total protein were measured, and then the concentration of the cell active material (pg / mL) was measured. Divided by concentration (mg / dl), the unit was analyzed to be gramgram (pg / mg total protain: TP) of the total protein of picogram / total protein of the cell active material. The amounts of IL-2, IL-4, IL-6, and TNF-α in the herbal and antibiotic groups were compared, and the amounts of IL-2, IL-4, IL-6, and TNF-α in the mucin and serous groups, respectively. Also compared.

(5) results

Cell activity associated with nonspecific and specific immune responses by separating exudate from the ears of the antibiotic-treated group (antibiotic group) and the group prescribed the composition of the present invention (herbal medicine group) among patients with recurrent otitis media The material was quantified by ELISA method.

a. The amounts of cell activators in the herbal and antibiotic groups were compared in Table 1.

IL-2 IL-4 IL-6 TNF-α Chinese medicine group (pg / mL) 1024.11 159 1246 61.09 Antibiotic group (pg / ml) 207.25 82.91 2651.8 219.9

In other words, IL-2 and IL-4 were higher in Chinese medicine group, and IL-6 and TNF-α were higher in antibiotic group.

b. The value of IL-2 divided by TP is shown in Table 2.

Highest Lowest Average Chinese medicine group (pg / mg) 19.44 0.236 5.85 ± 2.35 Antibiotic group (pg / mg) 2.36 0.063 0.761 ± 0.25

The Chinese medicine group was significantly higher than the antibiotic group (P <0.05).

c. Table 3 shows the IL-4 divided by TP.

Highest Lowest Average Chinese medicine group (pg / mg) 2.642 0.299 1.10 ± 0.255 Antibiotic group (pg / mg) 0.656 0.196 0.39 ± 0.038

The Chinese herbal medicine group was significantly higher than the antibiotic group (P <0.01).

d. Table 4 shows the IL-6 divided by TP.

Highest Lowest Average Chinese medicine group (pg / mg) 21.719 0.674 7.329 ± 2.73 Antibiotic group (pg / mg) 30.273 0.154 10.23 ± 3.12

The Chinese medicine group was significantly lower than the antibiotic group (P <0.05).

e. The value obtained by dividing TNF-α by TP is shown in Table 5.

Highest Lowest Average Chinese medicine group (pg / mg) 1.707 0.011 0.39 ± 0.19 Antibiotic group (pg / mg) 1.622 0.479 1.07 ± 0.1375

The Chinese herbal medicine group was significantly lower than the antibiotic group (P <0.01).

f. The effusions of antibiotics and Chinese medicine groups were classified into mucus and serous values, and their respective cell-active substance / protein values were compared.

Unit: pg / mg Chinese medicine group (11 ears) Antibiotics group (13 ears) Serous group (3 ears) Mucus group (8 ears) Serous group (8 ears) Mucus group (5 ears) IL-2 / TP Highest 7.91 19.44 2.36 1.81 Lowest 0.54 0.23 0.068 0.063 Average 3.611 6.966 0.62 1.008 IL-4 / TP Highest 2.52 2.64 0.45 0.65 Lowest 0.76 0.299 0.19 0.237 Average 1.686 0.888 0.337 0.46 IL-6 / TP Highest 9.56 21.70 30.27 19.57 Lowest 1.25 0.674 0.15 0.521 Average 4.335 8.703 11.45 8.5 TNF-α / TP Highest 1.70 0.937 1.91 1.62 Lowest 0.013 0.011 0.62 0.479 Average 1.048 0.144 1.13 0.99

g. The clinical features of the effusion, duration of disease, concomitant chronic sinusitis, and the presence of preoperative tympanostomy or ventricular intubation were as follows.

The serous and mucous extracts were divided into two groups. Antibiotics were more serous (61.5%), and herbal medicines were more mucous (72.7%). In comparison of the duration of disease, 53.8% of patients in the antibiotic group were more than 3 months old, and 81.8% of the patients in the Chinese medicine group were more than 3 months old. The proportion of patients with chronic sinusitis was 76.9% in the antibiotics group and 81.8% in the herbal group. Patients with a history of preoperative tympanostomy and tracheostomy were 7.69% in the antibiotic group and 63.6% in the composition group of the present invention.

(6) Conclusion

Experimental results show that Okamoto et al. Found that IL-2 and IL-4, which are involved in specific immune responses, were rapidly reduced in patients with persistent otitis media after antibiotic treatment and conservative therapy. In the study, it was observed that IL-2 and IL-4 were significantly increased in the Chinese medicine group to which the composition of the present invention was administered compared to the antibiotic group. In particular, since IL-2 has an autocrine function, it is the first indicator of cellular activity such as expressing the IL-2 receptor and promoting its own secretion. Therefore, the expression of IL-2 properly regulates the function of B cells and thus the antibody. In the case of IL-4, it plays a role in proper production, and in the case of IL-4, it causes antitumor activity through rapid infiltration of cytotoxic eosinophils in the tumor site. It is expected.

TNF-α and IL-6, which are directly related to the inflammatory response, can be seen to be increased in contrast to IL-2 and IL-4 in otitis media patients. Significant quantitative decrease was observed in the Chinese medicine group administered the composition. The concentration of IL-6 was higher in the mucous group than in the serous group, and it is estimated that the decrease of IL-6 concentration is related to the improvement of exudative otitis media. It is thought to be the mechanism by which exudative otitis media is cured. TNF-α has been reported to be associated with chronicity in patients with chronic exudative otitis media with prolonged morbidity and in relapsed patients with more than 2 ventilations.

In conclusion, the therapeutic effect of the present invention composition on recurrent exudative otitis media could be inferred from antibiotics.

In addition, the clinical findings of the patients showed that the effusion of antibiotics group was highly serous (61.5%), whereas the Chinese medicine group had more mucus (72.7%). The disease duration was more than 3 months in the antibiotic group (53.8%) and more than 3 months in the Chinese medicine group (81.8%). The history of preoperative tympanostomy and ventilator insertion was 7.69% in the antibiotics group and 63.6% in the Chinese medicine group, indicating that the Chinese medicine group had a more chronic condition (otitis) than the antibiotics group. Nevertheless, the ratio of the cell activator of the Chinese medicine group is better than the antibiotic group, suggesting the superiority of the treatment of the composition of the present invention for recurrent exudative otitis media in children.

In addition, 79.1% of the patients with recurrent otitis media with chronic sinusitis had a relatively high proportion, indicating that there is a strong link between chronic sinusitis and recurrent otitis media.

Through these overall results, the composition of the present invention was found to be an effective prescription for the treatment of otitis media patients by regulating the production of cellular active substances involved in the inflammatory response in otitis media. More research should be done on whether to regulate the production of substances.

As can be seen from the above experiment, the composition of the present invention is allergic to acute and chronic allergic rhinitis (including chronic sinusitis), allergic dermatitis, allergic otitis media (including recurrent otitis media), allergic conjunctivitis and allergic asthma. It can be usefully used as a prophylactic and therapeutic agent for diseases.

Claims (7)

As an active ingredient, Gilkyung, Golden, Jisil, Hyeonggae, Shiho, White Paper, Count, Cheongung, Dongguk, Windproof, Bridge, Licorice, Geumeunhwa, Pogongyoung, Cheonhwabun, Yugeunbaekpi, Hwanggi, Baekchul, Saengjihwang, Cheoncho, Shin Yihwa, Changja, Sangbaekpi, A pharmaceutical composition for preventing and treating allergic diseases, comprising extract of a mixture of half, horseback riding, rooting, and peppermint. The pharmaceutical composition according to claim 1, wherein the allergic disease is acute or chronic allergic rhinitis, chronic sinusitis, allergic dermatitis, allergic otitis media, allergic conjunctivitis, or allergic asthma. The pharmaceutical composition according to claim 1, wherein the mixture further comprises one or more selected from the group consisting of creation, dermis, cod, nutmeg, falcon, sessin, keg, moth, and oyster. The method of claim 1, wherein the mixture is Gilgil, golden, fruit, hyeonggae, shiho, white paper, earl, cheonggung, donkey, windproof, duct bridge, licorice, gold silver flower, pogongyoung, cheonhwabun, yugeunbaekpi, Astragalus, baekchul, raw sulfur, cheoncho, Shin-Ihwa, Chang-za, baekryepi, halves, horseback riding, rooting, and peppermint 4-6: 2-4: 3: 3: 3: 3: 4: 4-6: 4: 4-8: 2: 2-6: 4-8 : 6-12: 8-12: 4: 6-12: 6-10: 4-8: 4-8: 2: 2-4: 4-6: 4-6: 4: 2-4: 4-8 : Pharmaceutical composition containing by weight ratio of 2. 5. The method of claim 4, wherein the mixture has a weight ratio of 4: 4: 4: 4: 2-4: 2: 3: 4: 8-10; A pharmaceutical composition further comprising at least one member selected from the group consisting of uiyiin. Gilkyung, golden, fruit room, hyunggae, shiho, white paper, ear pear, cheongung, donkey, windproof, bridge, licorice, gold silver flower, pogongyoung, cheonhwabun, yugeunbaekpi, hwanggi, baekchul, saengjihwang, cheoncho, shinyihwa, changja, baekbaekpi, banha, horse riding A process for preparing a composition according to claim 1 by mixing an extract of a mixture of, root, and peppermint with a pharmaceutically acceptable carrier. 7. The method according to claim 6, wherein the mixture is a mixture of one or more extracts selected from the group consisting of creation, dermis, coriander, nutmeg, falcon, sessin, neck, moth, and oyster.