KR20130112237A - Use of treating and relaxing of snore and sleep apnea syndrome of mistletoe and composition comprising thereof as active ingredient - Google Patents

Abstract

PURPOSE: A mistletoe extract is provided to effectively treat and alleviate snoring and sleep apnea. CONSTITUTION: A mistletoe extract treats and alleviates snoring and sleep apnea and is used as a relief agent. A drug composition for treating and alleviating snoring and sleep apnea contains 0.05-30%(w/w) of mistletoe or the extract as an active ingredient. A product containing mistletoe as an active ingredient is manufactured by sterilizing mistletoe at 121°C for 15-30 minutes.

Description

Use of treating and relaxing snoring and sleep apnea of mistletoe and pharmaceutical composition containing the same

The present invention relates to the use of mistletoe for the treatment and alleviation of snoring and sleep apnea and to pharmaceutical compositions containing it as an active ingredient.

Conventional techniques related to compositions for snoring relief and methods of snoring are well known and are briefly listed as follows.

A method of reducing vibration noise by distributing snoring in the upper respiratory tract tissue where a snoring occurs using a lubricant.

By taking or applying the drug using the characteristics of the herbal ingredients, the snoring is reduced by the friction noise caused by the air inflow resistance that breathes in the narrow passage by the muscle relaxation of the bronchus (Uvula), palate (palate) tissue How to mitigate this.

Pharmacologically snoring noise reduction by taking organic drug compounds or by applying them to the site of development.

In combination with drugs to relieve upper airway narrowing during sleep.

How to remove the bronchial snoring without using the composition or applying it to the bronchial tissue by using a surgical technique.

In addition to physical compositions, methods of relieving snoring by physical exercise or lifestyle improvements.

Despite the development and application of the above methods, the snoring method of snoring has not been improved and continues to give patients both sleep disorders and companions an uncomfortable sleep and general life.

A review of domestic and international developments that have been developed to date regarding the manufacture of snoring relief compositions:

Korean Patent Publication No. 10-0852745 (August 1, 2008)

Republic of Korea Patent Publication No. 10-2010-0043010 (2010.4.27)

United States Patent 4876283 (Oct. 24th. 1989)

United States Patent Application No. 20110269839 (Published date 2011.3.11)

Korean Patent Application Publication No. 2003-0063671 (published 2003.7.31)

Suggestions on snoring effectiveness effects (Clickindia 19th.May.2010, Internet File)

U.S. Patent 6,187,318 B1 (Feb ,. 13,2001)

Republic of Korea Patent 10-0852745 (2008.8.11)

Sci Pharm. 2011. Vol.79, 145-155, www.scipham.at

Graduate School of Oriental Medicine, Daegu University Byung-Sung Kim, Master Thesis 2010. 2.

Korea Patent Publication No. 10-0852745 (2008.8.11)

Patents related to lubricating herbal composition are representatives of herbal medicines affecting snoring in human body and composition developed as various herbal medicines by lubricating vegetable seed oil components with natural resources. 10-2010-0043010 (April 27, 2010) discloses a patent application for taking a functional herbal medicine such as cheongungung as a tannin acid, alum and herbal ingredients for tablet and candy compositions.

A review of US Patent 4876283 (Oct. 24th. 1989):

The history of development of snoring treatment and mitigating agent is known as pharmacological drugs such as Ambroxol-HCl, Bromoexin, and Benzalchoniumchloride, Chlorbutanol. Organic pharmaceutical compounds such as Chlororbutanol are used. It was also registered in US Patent 5,569,679 (Oct. 29th, 1996) and tried to reduce snoring noise using methylsulfonyl methane. According to French Patent 2,859,105, hyaluronic acid salt and fungicide components , A patent that is characterized by the use of anti-inflammatory chlorhexidine gluconate (Clorhexidine gluconate) is registered as a representative, US Patent Registration No. 6,187,318 B1 (Feb. 3, 2001) vegetable fatty oils (seed oil, olive oil, almonds) And other patents that use vitamins (Vit. B, C), carrageenan, and magnesium magnesium silicate (Vegum).

Recent US Patent Application Trends:

Anti-inflammatory fungicide Chlorhexidine-based disinfectant, which had been popular many years ago, tends to revert back to anti-inflammatory fungicide formulations, and the application of application number 20110269839 (published on March 1, 2011) is used as a thickener relieving agent. Hyaluronic acid salt, a saccharide polysaccharide component, has developed a special gel, along with the development of a patented product.

In terms of such patent trends, in the case of Korean Patent Application Publication No. 2003-0063671 (published 2003.7.31), unfortunately, similar patent formulations were applied at the same time, but similar patent contents were registered at that time. It seems that the patent registration was rejected due to insufficient proof of good work and incomplete guarantee.

The view that bronchial sprays do not work well in some cases:

Although this view was in a foreign case (Clickindia 19th.May.2010, Internet File), subsequent use of such a product resulted in snoring and inflammation of the bronchus, which was not enough to improve snoring, but snoring was a relaxing effect. This trend seems to have been acknowledged. In general, there are many opinions that users should improve their habits along with the use of snoring products because statistics show that the snoring improvement product is physiological action that is inevitable when snoring is physically older in life.

Anyone can see and see the facts on the Internet Site, and even if the drug is used, the symptoms of snoring (hypertension, chronic bronchitis) in addition to simple habits and self-improvement will rarely improve. It is a doubt. Therefore, snoring products that have improved over the years should continue to be released and at the same time improve their lifestyles.

Lifestyle improvements with the use of bronchial spray products:

As is well known, it can be summarized in several ways. Essentially, snoring is caused by physiological rhythms. This is a symptom that can not be awakened by the sleeping person, and the person sleeping next to him knows snoring, but he is not aware of snoring.

During the resting (night) diastolic of this bronchial activity, lubrication of tissue skin mutual contact of the bronchus is maintained and the application of the lubricant is maintained (increasingly thickening and fragrance oil components) to treat the inflammation and to maintain lubrication. Preventing bronchial tissues from sticking together ensures a breathing pathway and makes you breathe tightly (sleep apnea, Apnea) and barely pass through your breath. This is simply a phenomenon.

How to improve snoring products and daily exercise gains

Firstly, it helps to restrain excessive drinking (drinking, overeating), maintain weight as a standard, exercise appropriately, lower blood sugar, use snoring spray appropriately, and stress your body physically and excessively Tired of the symptoms do not improve. This emphasizes the gradual physical rhythm of using spray formulations.

Recommend self-diagnosis with use of spray formulations:

This is a very well known method, and it's a very simple method: close your mouth and close one's nose with your hands and do a breathing exercise, close the other nose, close your mouth and breathing, evaluate your breathing and vice versa If you try to block the hole and breathe only through your mouth, you can observe your breathing condition (the level of breathing discomfort), and you can see which one is better to breathe through your nose and breathing through your mouth. To do that. These self-diagnosis symptoms indicate that proper use of snoring spray formulations can alleviate snoring.

Of course, if you lie down to prevent snoring in a fundamental position, the Uvula may be pressed against the root of the tongue, and it may be in close contact with the enlarged tonsil or the thickening of the throat wall. Whenever you take a break, you may hear vibrations. To prevent this, sleep on your side, but on the other side of your heart, or sleep on the other side of your heart (less pressure on your heart) rather than sleeping straight. Can be improved. However, the method of sleeping sideways is that the body senses the burden on the organs of the body and sleeps, turning the body from side to side, turning around and making it more uncomfortable to sleep, so sleeping comfortably and using this spray preparation before going to bed The view that this is beneficial is recognized in many of the above patents and snoring in specialized clickic.

The present invention provides the use of mistletoe for the treatment and alleviation of snoring and sleep apnea.

Another object of the present invention relates to a pharmaceutical composition containing mistletoe as an active ingredient for the treatment and alleviation of mistletoe snoring and sleep apnea.

Another object of the present invention relates to a pharmaceutical composition containing mistletoe and a medicament commonly used for this purpose for the treatment and alleviation of mistletoe snoring and sleep apnea.

The present invention is to add a component extracted from mistletoe (Mistletoe) medicine to the components that are commonly used as a treatment and relief agent for snoring and sleep apnea syndrome to make a new formulation and compare the efficacy to treat an appropriate snoring disease And to achieve the invention and the development of the technology for producing a composition that can be used as an emollient.

In accordance with the intention of the Natural Product New Drug Research and Development Promotion Act (Law No. 6400 Government Organization Act), the present invention has been endeavored to develop in terms of welfare and resource utilization for national health. As a result, mistletoe (mistletoe) is a herbal medicine recently approved as a rare drug as an anticancer drug and has been used as an anticancer drug in Europe for a long time. Domestic famous herbal medicine, but still snoring. Mistletoe, which has never been used as a drug for sleep apnea and pressing of scissors, is used as a herbal medicine to alleviate symptoms such as snoring and to improve the lives of patients. To provide a method and a finished novel composition.

Mistletoe extract was significantly more effective in reducing snoring compared to existing products, so that statistical analysis was not necessary. Therefore, the mistletoe extract of the present invention has an excellent effect on the treatment and relief effect of snoring and sleep apnea syndrome.

OBJECT OF THE INVENTION The present invention generally relates to the use as a therapeutic and mitigating agent for snoring and sleep apnea syndrome, and to a pharmaceutical composition containing the same as an active ingredient.

Another object of the present invention is to provide a pharmaceutical composition further comprising a substance commonly used for snoring and sleep apnea syndrome in addition to mistletoe as a pharmaceutical composition for treatment and alleviation of snoring and sleep apnea syndrome.

In the present invention, a formulation in which a mistletoe (Mistletoe) drug extract is extracted from a conventional drug used for the purpose of treating and alleviating snoring and back apnea syndrome, which is commonly used, is prepared in a high-level subunit subunit, and its efficacy is improved. In comparison, to prepare a composition that can be used as a treatment and mitigator for the appropriate snoring and sleep apnea syndrome disease.

The present inventors have found that mistletoe herbal medicine contains retin, polysaccharide polysaccharides, flavonoids, etc. among the special components contained therein as its immune function-enhancing action, thickening ingredient, and anticancer ingredient. It is the motive that was invented after evaluating it as valid.

Composition and Working Principle of the Invention and Development of Effective Formulations:

When explaining the herbal mistletoe (mistletoe) used in the present invention, this herb is distributed not only in Korea but also all over the world, and it is a plant that appears in the synonym and the Bible and has many mysterious topics (story) in the East and West. It is a plant.

The meaning of the name is Chinese ancestors (mean of mulberry parasitic plants), the Korean name is mistletoe (winter fleshing plants, barely living parasitic plants), and the English name is mistletoe (Mistletoe strong bird's claw, meaning of the legendary mysterious tree) It is a herbal medicine listed in the British Pharmacopoeia (BHP 1996) and German Pharmacopoeia (DAB 1996).

A plant ecologically dicotyledonous plant, an evergreen parasitic plant belonging to the family of Mistletoe (Viscaceae) and Loranthaceae. Its appearance is rooted in tall tree (oak or chestnut) and absorbs moisture from the host, so that it can self-assimilate itself, bloom green leaves and flowers and bear fruit all year round. The plant is still green and is modeled as if it is a house. It grows and grows up and may be mistaken as a magpie house. The shape differs slightly depending on the various host trees. Among them, the Viscum album is a well-known plant in Europe that has been used for indoor and outdoor decoration with candles and drops at Christmas. The story of a girl standing under this tree with Valentine's Day is also present. The plant ecology also thought that this plant was simply a parasitic plant that pollinated host plants. However, some plant foresters have found it in host tree plants (oak, pine, alder, cherry, chestnut, trees, camellia, etc.). It is also known to have a symbiotic relationship. In other words, because the tree bears fruit, birds fly to eat for food, and the caterpillars on the tree eat the same pests, and many birds come to drop feces and provide urea fertilizers. According to the movement of these birds, winter seeds are spread from birds' beaks to trees.

This mistletoe tree has many legends, and ripe fruit is collected, used as medicine, boiled out water with water and drinked as tea (SciPharm. 2011. Vol.79,145-155, www.scipham.at). It was sacred in Europe.

When the mistletoe community was found on the battlefield, both sides stopped the battle and gathered it as medicine, which was regarded as a sacred tree given by the sky where lightning fell on the tree.

Many papers have been published in the Korean Journal of Plant Herbal Medicine and Forestry, and they have been studied at a considerable level due to their efficacy. In Europe, they are officially licensed and prescribed as anticancer drugs.

The U.S. FDA has not yet approved the drug's contingent request for anticancer drugs, and its position has been revealed through the National Cancer Institute. (National Cancer Institute, Mistletoe Extracts (PDQ), http://www.cancer.gov/cancertopics/pdq/cam/mistletoe/ ~-). It is in the form of a Q & A, which is why the US FDA does not permit it even though it is used in many clinical trials and as an anticancer drug in Europe. The answer is that there is insufficient evidence that it is obviously effective in the treatment of certain more specific cancer symptoms, and that immunization against long-term cancer is difficult to obtain as a direct treatment. However, it is true that anyone is using this herbal medicine as a health and health food, so it is not used for treatment, but it is not approved for treatment, but it is used by society. It suggests that.

According to Sanyacho Dongbobom (ed by Jang Jun-geun), mistletoe is eaten as a medicine to treat gastrointestinal diseases, drink 30-40 grams of herbal medicine as a folk medicine, and drink it with water, diuretic effect of neuralgia, arthritis, and nutrient for pregnant women.

Recently, a number of reports on herbal extracts such as anticancer effect and hypertension treatment have been reported in Korea. The Rural Development Administration also provides special research support and countermeasures regarding increased production of mistletoe.

In particular, a comprehensive paper on mistletoe was published in February 2010. The paper was tested on domestic and international research data, commercial contents, and comparative analysis of components. (Department of Oriental Medicine, Graduate School of Oriental Medicine, Daegu University Byung-sung Kim, Master's Thesis, 2010. 2.).

Medical herbalism, Vol. 3 (1), 1.4-6 has also reported blood pressure-lowering effects of this mistletoe in circulatory drug studies, but patents and use of snoring treatment and symptom relief in foreign countries or in Korea are also reported. There are no reports on the application yet.

About this mistletoe which has various effects ranging from medicinal to panacea, the inventors of the present invention prepared the composition as a constituent of the snoring treatment and palliative, investigated the action, and obtained the excellent effect and completed the invention. The amount used does not show any side effects such that the amount of one bag (1.94 grams to 2.0 grams) used in general commercial tea is included in the 30-milliliter manufacturing unit packaging unit (less than one-twentieth of the normal dosage) The mistletoe used was adjusted to a safe amount at which the components of the protozoa were measured. The main ingredient of mistletoe herbal medicine is easily extracted and identified from the bag powder of this simple herbal medicine tea. The main ingredient is classified into protein and non-protein ingredients (Sci Pharm. 2011. Vol. 79. 145-155).

Protein Ingredients:

It is reported that anti-tumor effect substance is included as a component of anti-cancer and non-lactin as a component of lectin and as a non-lactoxin component. A considerable amount of research has been reported on these.

Nonprotein Ingredients:

Alkaloids and flavonoids (Rutin, Quercetin derivatives) and polysaccharides (Polysaccharides) are contained in large quantities. The inventors of the present patent application plan to use that the polysaccharide component of mistletoe has a snoring effect.

In addition, the present invention was completed in anticipation of a lubricating effect on the bronchial mucosa by the effect of the blood pressure lowering effect of the mistletoe component, the effect of relieving inflammation, and the polysaccharides such as hyilurosan.

A paper on the extraction and analysis of these components (Sci Pharm.) Was referred. The mistletoe flavonoid content was selected as Rutin as an indicator. The rationale for this setting was to adopt the basis for the approval of the mistletoe extract injections from the KFDA Ophthalmology Screening Results.

Pharmaceutical agents that can be used in the present invention, Ambroxol-HCl, Bromoexin (Bromohexin), Benzalchonium chloride (Benzalchonium chloride), Chlororbutanol, Methylsulfonyl methane as a fungicide , Hyuronic acid salt, Chlorhexidine gluconate, vegetable fatty oil (oil oil, olive oil, almond oil), vitamins (Vit.B, C), carrageenan, magnesium aluminum silicate ( Magnesiun Aluminum silicate, Veegum) and Chlorhexidine, an anti-inflammatory fungicide, can be exemplified.

Next, the present invention will be described in more detail as Examples and Experimental Examples.

Example 1

Preparation of General Conventional Pharmacological Compositions of Spray Liquids with Snoring Relief:

In general, the snoring was used and prepared as a blending type and manufacturing method of the raw materials used in the relaxation method. The conventional manufacturing method means that the dissolution aid thickener used as an excipient in the raw material is first dissolved in an aqueous solution first, followed by swelling, then increased by the dispersing method with water, and the main agent and the preservative solution dissolved in the separate aqueous solution are mixed with the thickener, followed by high-speed emulsification. It is a method of completing the preparation of the drug by horizontally homogeneous mixing. Although the raw material of the pharmaceutical is different, the manufacturing method is generally used. However, if it is impossible to manufacture in the usual way in this process, it is manufactured under the conditions given by subdivision.

This conventional product is a product made by the general pharmaceutical manufacturing method of the product which is on the market under the permission of KFDA. This manufacturing method can be manufactured by the conventional method shown by literature.

0.05 parts xanthan gum as a raw material, surfactant twins as an excipient, 0.01 to 0.02 parts, ethanol 2.5 parts, chlorhexidine gluconate 0.003 to 0.005 parts, hyaluronic acid 0.05 to 0.1 parts, preservative parabens 0.2 parts, vegetable flavors, Purified water was added to make 100 parts in total.

Spray formulation packaging methods according to the use of the preparation:

Each raw material was precisely taken into a preparation tank, mixed with a high-speed emulsifier, and filtered. During the process, the product was tested for specifications, and each bottle was filled and packaged in a spray container with 30 to 50 ml each. The packing amount was 30ml per bottle, and the spray nozzle was selected so that 0.12 ~ 0.13ml was sprayed in one spray.

Example 2

Surfactant was prepared and packaged by replacing 0.05 to 0.1 parts of Carrageenan instead of twins.

Example 3

Surfactant was prepared and packaged by replacing 0.05 to 0.1 parts of alginate (Sodium alinate) instead of carrageenan.

Example 4

Mizle herbal supplements snoring relief spray liquid manufacturing method:

12.0 parts of Mizle crude herbal powder {11.64 X 1.03 (1.94 X 6 X 1.03)} was added to 180 parts of sterilized purified water, boiled for 5 minutes, cooled, filtered, and used as a thickener raw material according to the conventional manufacturing method of Example 1 above. The swelling was added according to the working process sequence, and a separate preservative was dissolved in 20 parts of sterile water, and the two solutions were mixed with a high-speed rotary stirrer to make 200 parts in total. The solution was filtered and filled in 30 ml spray-packed containers and sealed to obtain a product.

Basis of Mizelto Herbal Consumption:

The reason for this is that 1 bag of mizelto tea (commercially-distributed product, average of 1.94 grams in Germany and 2.0 grams in domestic distribution) contains extract ingredients in one bottle of 30 ml of product. Vol. 79, 145-155), the test method described in Protozoa Extraction Method was applied. The snoring spray solution preparation method was developed and adopted.

This export method is a pharmacological improvement of the traditional tea drinking method, which is a simple method of boiling traditional mizle herbal powdered tea, which is traditionally used in the private sector, by boiling water for 5 minutes.

Example 5

Preparation method of snoring liquid spray product containing mistletoe extract:

How to prepare mistletoe using crude herbal extract

Mistletoe herbal medicines are packaged in two gram packages (eg, Jeju Hannibo Mistletoe) and hay (Daegwallyeong Agricultural Association..Gangneungseong 2) products in the form of raw herbs. Hay products were first purchased and used. 12 g of the crude drug was added to 180 ml of sterile purified water and boiled for 5 minutes and cooled to room temperature. 0.1 g of xanthan gum was added to the solution, followed by swelling. Then, 0.04 g of polysorbate was added, 0.2 g of hyaluronic acid was added and stirred. Separately, 0.05 g of preservative chlorhexidine glucuronic acid solution, 0.3 g of preservative paraoxybenzoic acid, and 0.02 g of menthol were added to 5 ml ethanol. After dissolving, the solution was added to the stomach mistletoe extract and stirred with a high speed emulsifier. The mark was adjusted so that the whole was 200ml, the final emulsification and agitation was made into the final volume product, and then 30ml each was packed and packed into individual spray bottles to complete the product.

Example 6

Method of using mistletoe tea extract: For reference, crude and tea beverage products differed only from particles of herbal medicine, and there was no significant difference in the extraction (boiling method) of the eluting flvonoid content (marker rutin Rutin).

Mistletoe tea herbal or commercial products (2 g each encapsulated product) were prepared by the method of preparation of 4.1. Mistletoe tea extract 1.2g (1/10 of the raw material in the manufacturing method of Example 5) is taken, and 180ml of sterile purified water is added to produce the snoring product in the same manner as the manufacturing process.

Example 7.

How to make liquid preparation with mistletoe tea extract only

Mistletoe crude commercial 12g of commercial product using only 180ml sterile purified water boiled and cooled for 5 minutes as used for tea beverages, filtered to 5 microg and the whole was prepared in 200ml by sterile purified water. In this case, no preservatives, hyaluronic acid salts, etc. were added. They were prepared for use and used for snoring alleviation within 1 week. In the long-term storage of this filtered formulation was found to be very fine precipitated stability problem was seen, but the use of a suspending agent in the method of Example 1 to Example 6 was stable for a long time.

Example 8.

This final formulation solution without the preservative was prepared in accordance with Example 7 by using a mistletoe herbal medicine dried sterilized by autoclave solution (sterilized for 120 minutes at 120 degrees Celsius) and the original medicine as it is steam sterilized for 120 minutes 30 minutes.

Example 9.

In the method of Example 4, a solution containing mistletoe in a content of 2 g / 30 mL and 0.5% of bromohexine, a pharmaceutical organic substance, which is a cough relieving agent was prepared.

Example 10.

By the method of Examples 4 and 9 to prepare a solution of 0.5% ambroxol hydrochloride instead of bromohexine.

Experimental Example 1

Set of Indicators:

Sci pharm 2011, S. Jager et al Data and product test flavonoid content in the FDA's rare drug mistletoe extract injection safety review.

Analysis and Results of Extracts from Mistletoe Protozoa (Comparison of Rutin 3 Carb):

HPLC Content Analysis by Mistletoe Extraction Method:

Routine content 0.113% ~ 0.124% in mistletoe,

Analytical Reference: Sci Pharm. 2011. Vol. 79, 145-155.

Determination of Rutin Content in 70% Ethanol Extract

25 g of Mistletoe (Daegwallyeong) was measured using 2.5 ml of 70% ethanol for 1 week at room temperature using an extract filtrate.

HPLC method (Condition *) resulted in 0.35% of rutin. (Rutin trihydrate standard used: Elcom Science, Seoul National University).

HPLC analysis conditions: instrument YL 9100 HPLC (Korea),

C18 column, WATERS Sunfire, 5micro.m 4.6X 250mm

Mobile phase, 2.5% acetic acid: acetonitrile = 80: 20

Flow rate 0.8ml / min, Injection 10micro-liter UV 360nm.

Rutin about 8min. retention time.

(Ref: Fagopyrum Vol. 23 37-43 (2006), Ping JIANG et al.).

Experimental Example 2

Sterilized purified water heated for 5 minutes

Mistletoe 25g / 2.5L purified water from Korea (from Jeju Island)

Analytical Methods (homologous) Rutin Content Contains 0.55% Rutin.

Comparison of foreign data: Korean mistletoe has a high content of herbal routines.

Comparative Example 1

Manufacturing method of snoring liquid spray by the usual method of general domestic distribution products:

Using only the sterilized purified water without using the mistletoe extract to prepare a snoring relief product using the manufacturing process of Example 5.

Experimental Example 3

Snoring Noise Reduction (Improvement) Comparison Effect Test:

General comparative test using two products, one containing mistletoe extract and one common product.

For both products, the snoring noise level and comfort were statistically compared.

Ten candidates were evaluated for two days on both sides of the product, with snoring noise reduction measured according to the following test method.

Before taking the drug, the snoring noise level is input into the recorder (normal recorder or aphone-type mobile phone type), the degree score is recorded on the self-diagnosis level table, and the result is recorded the day after the drug is administered on the day. After 3 days of administration, record in the same way, and after daily rest, the other self-administration the next day after 3 days of administration, the applicant's evaluation and record the noise level.

For the two specific products, the noise comparison is recorded as a 0.5 point difference grade (7 grades in total) between grades according to the self-diagnostic grade 4 method.

For sleep apnea measurement, ECG, a direct measurement method, was not performed. (Apnea symptom: inability to breathe for 5 seconds and general evaluation symptom for 5 hours without breathing for 1 hour) Detailed snoring noise comparison is sprayed to the area around the throat of the bronchial airways twice before sleeping and after falling asleep Or, by using a smart phone, the voice memo function allows the user to record more than 2 hours of initial sleep, and to compare the noise levels between the two products.

The analysis method of mechanical noise comparison analysis is classified into four grades based on the noise level for two products (tested product without mistletoe and test product for snoring respectively). Judged and given a grade of 0.5 points for each grade.

Subsequently, class 4 is divided into 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, and 4.0) and compared with the initial setting before drug administration by class 7. (Domestic Patent Registration 10--852745, 2008.8.11 Grade 4, U.S. Patent 6,187,318 B1 Feb.13.2001.U.S. Patent Noise Level: Grade 5).

Among the two products used by each of them, as described above, the self-satisfaction is classified into 4 grades and 7 grades in total, and divided into normal, slight discomfort, discomfort, and extreme discomfort. Compared.

Statistical processing of self-satisfaction measurement table by noise level analysis

The statistical significance and effectiveness of the pilot clinical writing statistics are based on the Wilcoxon signed ranks test, a nonparametric inference method (the statistical method used when the population normal distribution is uncertain or absent). We analyzed the significance of snoring improvement of mistletoe extract with respect to the conventional prescription by the method of determining critical values for the null hypothesis.

As a result of analysis, the existing prescription was more effective than this drug (statistics omitted). Two prescriptions by concentration of mistletoe extract were alternative hypotheses that both products could reject the null hypothesis, and the research hypothesis was effective. Red significance (Tables 1 and 2, 3),

The deviations between the existing prescription products used to evaluate the mistletoe effect of the two concentrations (Table 1 and Table 2) were the same as 5, with n = 5 and Rank results W + = 9 and W- = -6 Wilcoxon SR The P value 0.4063 (> 0.05) on the Test Probability Levels did not allow the null hypothesis to be rejected. Therefore, it was meaningful to compare two concentrations of mistletoe-containing products with existing prescription products and evaluate them simultaneously (statistics omitted).

Concentrations of these two mistletoe-containing products (Mistletoe 0.02g / spray solution 30ml) were not as effective as the mistletoe-free products (old prescription products not used) (effect statistics omitted).

Evaluation Score Table for Commercial Product Prescription A and Mistletoe Prescription B Product (0.2g / 30ml) (Wilcoxon S.R.Test) Participation No.  A (X)  B0.2 (Y)  X-Y a. [X-Y] Rank of absolute Signed rank  Remarks   One   2.0   1.0   +1.0   1.0 8  +8   2   3.0   2.5   +0.5   0.5 4  +4   3   2.0   2.0    0   4   2.5   2.0   +0.5   0.5 4 +4   5   2.0   1.5   +0.5   0.5 4 +4   6   2.0   2.5   -0.5   0.5 4 -4   7   2.5   2.0   +0.5   0.5 4 +4   8   2.5   2.0  +0.5   0.5 4 +4   9   2.0   1.5   +0.5   0.5 4 +4   10   2.0   2.0    0 Result:
Significant W + = 32W
W- = 4 N = 8
Critical value = 4

P Value (n = 8 W- = 4) = 0.0273 <0.05 (Significance)

Evaluation Score Table for Commercial Product Prescription A and Mistletoe Prescription MSB Product (2.0g / 30ml) (Wilcoxon S.R.Test) Participation No.  A (X)  B2.0 (Y)  X-Y a. [X-Y] Rank of absolute Signed rank  Remarks   One   2.0   1.5   +0.5  0.5  4  +4   2   2.5   2.0   +0.5  0.5  4  +4   3   2.0   1.5   +0.5  0.5  4  +4   4  2.0   1.5  +0.5  0.5  4  +4   5   2.5   2.0   +0.5  0.5  4  +4   6   2.0   2.0   0   7   2.0   2.0    0   8   2.5   2.0    +0.5  0.5  4  +4   9   2.0   2.0    0   10   2.5   2.0    +0.5  0.5  4  +4 Result:
Significant W + = 28
W- = 0 N = 7
Critical value = 2

P value (n = 7, W- = 0) = 0.0078 <0.05 (Significance)

Prescription product using prescription A product and mistletoe only (Example 7) MSC product (2.0g / 30ml) Evaluation Score (Wilcoxon S.R. Participation No.  A (X)  MSC (Y)  X-Y a. [X-Y] Rank of absolute Signed rank  Remarks   One   2.0   1.5   +0.5   0.5 5 +5   2   2.5   2.0   +0.5   0.5 5 +5   3   2.5   2.0  +0.5   0.5 5 +5   4   2.5   2.0   +0.5   0.5 5 +5   5   2.0   1.5   +0.5   0.5 5 +5   6   2.0   2.5  -0.5   0.5 5 -5   7   2.5   2.0   +0.5   0.5 5 +5   8   2.5   2.0  +0.5   0.5 5 +5   9   2.5   1.5   +1.0   0.5 5 +5   10   2.0   2.0    0 Result:
Significant W + = 40
W- = 5 N = 9
Critical value = 6

P Value (n = 9, W- = 5) = 0.0195 <0.05 (Significance)

Summary of results

Mistletoe 30ml extract (2.0g) in the normal dose of 1 bag was significantly more effective in reducing snoring compared to existing products (Table 2). The product containing one dose (Table 1) is statistically significant, but mistletoe is preferred as a herbal tea because of its aroma and taste. It was also judged as. In addition, the mistletoe preparation containing 100% of this amount retained the mistletoe odor and was appropriately formulated, but the mistletoe component did not show any significant effect of snoring. Therefore, the effective concentration ranges from 0.2g / 30ml to 2g / 30ml of fine articulated bare flesh. The significantly selected mistletoe herb extract produced a snoring effect.

The results showed that preference for mistletoe-containing drugs was higher than existing commercial products, and snoring effect was compared between mistletoe herbal extracts. That is, snoring does not contain hyaluronic acid Na salt, which is the main ingredient included in the prescription, and mistletoe-containing products are mixed with menthol and preservatives. there was.

However, snoring effect was significantly reduced by mistletoe tea extract alone, but the long-term stability of the drug was slightly reduced (Table 3).

In addition, formulations containing bromohexine, ambroxol hydrochloride, etc., which are used to treat coughs, also had limitations in comparing effects with the significance measurement method of this patent showing the degree of relief of snoring (no significant difference, statistical omission). More scientific methods of measuring electrocardiograms, carbon dioxide emissions, etc. may be found.

However, sleep apnea symptoms, which are usually judged as pathological conditions that do not breathe for more than 5 seconds and are not breathed more than 5 times within an hour, can be evaluated by increasing the sensitivity of a general sound recorder. This measurement can be used to detect the symptoms of aggravating sleep during sleep.

As a result, it was most appropriate to use mistletoe as a therapeutic and mitigating agent for snoring and sleep apnea syndrome, in which 30 ml of the formulation was 0.02 g or more and 2 g.

According to these test results, applying mistletoe herbal medicine as a snoring snoring agent is an excellent way to personally improve healthy sleep rest and prevent dangerous sleep apnea. This mitigation development was completed.

Claims (6)

Use of Mistletoe (Mistletoe) Extract as a Treatment and Mitigation Agent for Snoring and Sleep Apnea Syndrome.
A pharmaceutical composition for treating and alleviating snoring and sleep apnea syndrome, which contains mistletoe or its extract as an active ingredient.
Contains mistletoe or its extract as an active ingredient, Ambroxol-HCl, Bromoexin, Benzalchonium chloride, Chlororbutanol, Methylsulfonylmethane (Methylsulfonylmethane), hyaluronic acid salt, chlorhexidine gluconate, vegetable fatty oils (seed oil, olive oil, almond oil), vitamins (Vit.B, C), carrageenan, A pharmaceutical composition for treating and alleviating snoring and sleep apnea syndrome further comprising at least one member selected from the group consisting of magnesium aluminum silicate (Vegegum) and an anti-inflammatory bactericide, Chlorhexidine.
The pharmaceutical composition of claim 2 or 3, wherein the active ingredient contains mistletoe (mistletoe) or its extract in the range of 0.05% to 30% (w / w).
The method of claim 2, wherein the active ingredient is mistletoe (mistletoe), which is sterilized at 121 ° C. for 15 to 30 minutes by autoclaving.
The method for producing a product according to claim 2, wherein the solution prepared without using a preservative is autoclaved at 121 ° C. for 15 minutes to 30 minutes.