KR100861677B1 - Composition comprising sulfur for treatment and prevention of liver disease - Google Patents
Composition comprising sulfur for treatment and prevention of liver disease Download PDFInfo
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- KR100861677B1 KR100861677B1 KR1020030056650A KR20030056650A KR100861677B1 KR 100861677 B1 KR100861677 B1 KR 100861677B1 KR 1020030056650 A KR1020030056650 A KR 1020030056650A KR 20030056650 A KR20030056650 A KR 20030056650A KR 100861677 B1 KR100861677 B1 KR 100861677B1
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- South Korea
- Prior art keywords
- sulfur
- hepatitis
- composition
- petroleum
- hbv
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- A—HUMAN NECESSITIES
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- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/04—Sulfur, selenium or tellurium; Compounds thereof
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/15—Inorganic Compounds
- A23V2250/156—Mineral combination
- A23V2250/1624—Sulphur
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- Medicines Containing Plant Substances (AREA)
Abstract
본 발명은 간염바이러스 억제 효능을 갖는 석유황 또는 유황을 함유하는 약학 조성물에 관한 것으로, 본 발명의 생약 조성물은 특히 B 형 간염 바이러스에 대한 억제활성을 가지므로 간염, 간경화증 및 간염과 같은 간질환의 예방 및 치료에 효과적인 건강기능식품 및 의약품을 제공한다.
The present invention relates to a pharmaceutical composition containing petroleum sulfur or sulfur having an inhibitory effect on hepatitis virus, and the herbal composition of the present invention has an inhibitory activity against hepatitis B virus, in particular, and thus prevents liver diseases such as hepatitis, cirrhosis and hepatitis. And health functional foods and pharmaceuticals effective for treatment.
석유황, 유황, 간염, 바이러스, 건강기능식품, 의약품. Petroleum sulfur, sulfur, hepatitis, viruses, dietary supplements, medicines.
Description
도 1은 본 발명의 석유황을 처리한 B형 간염 환자의 혈청 중의 HBV DNA 양을 비처리군과 비교한 그래프이고,Figure 1 is a graph comparing the amount of HBV DNA in the serum of hepatitis B patients treated with petroleum sulfur of the present invention compared to the untreated group,
도 2a는 본 발명의 조성물 투여전 CT 사진 이며, 도 2b는 본 발명의 조성물 투여후 간경변현상이 소실됨을 확인한 CT 사진이다.
Figure 2a is a CT picture before administration of the composition of the present invention, Figure 2b is a CT picture confirming the loss of cirrhosis after administration of the composition of the present invention.
본 발명은 석유황을 함유하는 간질환 치료 및 예방용 조성물에 관한 것이다.The present invention relates to a composition for treating and preventing liver disease containing petroleum sulfur.
현대의학이 발전하면서 세균질환은 항생제, 예방백신 등의 개발로 현저하게 억제되고 있지만, 바이러스 질환은 아직도 정복되고 있지 않을 뿐 아니라 오히려 대기오염, 환경오염 등을 통해 더 늘어나는 것으로 보고되고 있다. 그러나, 예방백신이 개발되어 있는 바이러스 질환은 일부에 지나지 않으며 바이러스성 독감, 간염, 무균성 뇌수막염 등을 비롯한 많은 질환들의 근본적인 치료법이 아직 개발되지 못하고 있는 실정이다.As modern medicine advances, bacterial diseases are markedly suppressed by the development of antibiotics and preventive vaccines, but viral diseases are not yet conquered, but rather are reported to increase through air pollution and environmental pollution. However, only a few viral diseases in which prophylactic vaccines are developed, and fundamental treatments for many diseases, including viral flu, hepatitis, aseptic meningitis, and the like, have not yet been developed.
B형 간염 바이러스(이하 HBV 바이러스라 함)는 헤파드나바이러스 (hepadnaviruses) 과에 속하며, 급성 간염뿐 아니라 간경변과 간암을 포함한 만성 간 질환을 유발하는 비세포병변(non-cytopathic) DNA 바이러스로 HBV 바이러스 유전자(genome)는 약 3,200 bp의 불완전한 이중 나선 구조로서 이완된 원형을 유지하고 있다. (Peutherer JF. Hepadnaviruses. in: Greenwood D, Slack RCB, Peutherer JF. Medical Microbiology 14th ed. Edinburgh: Churchill Livingstone, 1994; 527-540). Hepatitis B virus (hereinafter referred to as HBV virus) belongs to the family of hepadnaviruses and is a non-cytopathic DNA virus that causes acute hepatitis as well as chronic liver disease including cirrhosis and liver cancer. The gene is an incomplete double helix structure of about 3,200 bp, maintaining a relaxed circle. (Peutherer JF. Hepadnaviruses. In: Greenwood D, Slack RCB, Peutherer JF. Medical Microbiology 14th ed. Edinburgh: Churchill Livingstone, 1994; 527-540).
HBV 바이러스의 자기복제는 비리온(virion)이 간세포에 부착되면서 시작되는데 간세포의 핵에서 HBV 바이러스 DNA의 플러스 사슬(plus strand)의 합성이 완료되면 바이러스 유전자는 공유결합의 닫힌 환형의 DNA(covalently closed circular DNA, cccDNA)로 전환된다. 이 cccDNA는 프리게놈 RNA(pregenomic RNA)의 주형(template)이 되고 이 프리게놈 RNA(pregenomic RNA)는 다시 HBV 바이러스 DNA의 마이너스 사슬(minus strand)로 역전사된다. 이 cccDNA는 두 가지의 기원을 가지게 되는데 즉 새로운 바이러스 단편(virus particle)이 간세포 내로 들어온 것이거나 또는 세포질 내의 미숙 뉴클레오캡시드(immature nucleocapsid) 내에 있던 부분적으로 이중사슬화된 DNA(partially double stranded DNA)이다. 대부분의 항바이러스 제제는 이 cccDNA에는 거의 영향을 미치지 못하는 것으로 알려져 있는데(Locarnini S, Birch C., J Hepatol 30: 536-550, 1999) 이것은 항바이러스 제제를 사용한 치료를 중단할 경우 재빨리 혈청 HBV 바이러스 DNA가 출현하는 이유 로 생각된다. Self-replicating of HBV virus begins with the attachment of virions to hepatocytes. Once the synthesis of the plus strand of HBV viral DNA is completed in the nucleus of the hepatocytes, the viral gene is covalently closed. circular DNA, cccDNA). This cccDNA becomes a template of pregenomic RNA, which is then reverse transcribed into the minus strand of HBV viral DNA. This cccDNA has two origins: either a new virus particle has entered the hepatocytes, or a partially double stranded DNA that was in the immature nucleocapsid in the cytoplasm. to be. Most antiviral agents are known to have little effect on this cccDNA (Locarnini S, Birch C., J Hepatol 30: 536-550, 1999). This is because serum HBV virus is quickly resolved when treatment with antiviral agents is discontinued. It is thought to be the reason for the appearance of DNA.
만성 B형 간염의 발병기전은 자세히 밝혀져 있지 않으나 결정적인 요인은 면역반응의 장애로 인하여 바이러스의 증식이 계속되고 불완전하게나마 이를 제어하려는 면역체계의 반응이 지속되기 때문으로 추정된다. 이와 같은 이론적인 배경 하에 만성 B형 간염의 치료를 위하여 면역능을 강화시키는 약제와 바이러스의 증식을 직접 억제할 수 있는 항바이러스제에 대한 많은 연구와 시도가 있어왔다. 만성 B형 간염 치료의 목적은 HBV 바이러스의 자기복제를 억제하고 간염의 완화(remission)를 유지하는 것이다. 현재 만성 B형 간염 치료제로는 인터페론(interferon, IFNs)과 라미부딘(lamivudine)이 주로 사용된다. 인터페론은 항바이러스 효과와 증식억제, 그리고 면역조절기능을 가지고 있는데 특히 IFN-α는 HBV 바이러스의 자기복제를 억제하고 간질환의 완화(remission)를 유도하는데 매우 효과적인 것으로 알려져 있다. 그러나 IFN-α의 효능은 아주 잘 선택된 소수의 환자에 대해서만 제한적으로 나타난다는 한계가 있다. 또한, 가격이 비싸며 부작용이 많고, 주로 출생 직후에 시작한 감염이 문제가 되는 아시아권 환자에서 그 효과가 떨어지는 것으로 알려져 있다(Wong DK, et al., Ann. Intern. Med., 119: 312-323, 1993).The pathogenesis of chronic hepatitis B has not been elucidated, but the decisive factor is presumably due to the impairment of the immune response, which continues the proliferation of the virus and the immune system's response to incomplete control. Under these theoretical backgrounds, many studies and attempts have been made on drugs that enhance immunity and antiviral agents that can directly inhibit the proliferation of viruses for the treatment of chronic hepatitis B. The purpose of chronic hepatitis B treatment is to inhibit self-replicated HBV virus and maintain remission of hepatitis. Currently, interferon (IFNs) and lamivudine are mainly used to treat chronic hepatitis B. Interferon has antiviral effects, proliferation suppression, and immunomodulatory functions. In particular, IFN-α is known to be very effective in inhibiting HBV virus self-replicating and inducing remission of liver disease. However, there is a limitation that the efficacy of IFN-α is limited to only a few patients who are well selected. It is also known to be less effective in Asian patients, which are expensive and have many side effects, and infections that begin shortly after birth are problematic (Wong DK, et al., Ann. Intern. Med., 119: 312-323, 1993).
B형 간염은 치료도 중요하지만 그것보다도 치료가 불가능한 간암으로 전환되는데 있어서 B형 간염 바이러스가 관여하는 것을 막는 것도 매우 중요하다. 이러한 HBV 바이러스 증식은 대부분 간에서 일어나지만 일부는 비장, 신장, 췌장, 골수 등에서도 일어난다. 그러나 이러한 간 이외 장기에서의 증식은 조직 손상은 유발되지 않고 단지 HBV 바이러스만 증식된다. Hepatitis B is important to treat, but more importantly, to prevent the involvement of the hepatitis B virus in the conversion to incurable liver cancer. Most of the HBV virus growth occurs in the liver, but some occur in the spleen, kidney, pancreas, bone marrow, and the like. However, proliferation in these organs other than liver does not cause tissue damage, only HBV virus.
이와 같이 만성 B형 간염은 전신 질환의 특성을 띄고 매우 복합적이고 복잡한 형태의 발병기전을 가지며 궁극적으로는 면역계의 장애가 중요한 발병 원인이 된다. 그러나 타 연구분야에 비해 HBV 바이러스의 면역학적 병태생리 규명을 위한 실험실적 방법들이 충분히 개발되지 못하고 있어 현재까지도 여전히 B형 간염의 병태생리상 면역학적 기전의 규명은 매우 요원한 상태이며, 이미 HBV 바이러스에 감염되어 있는 환자들에게 도움이 될만한 치료법 역시 거의 없다.As such, chronic hepatitis B is characterized by systemic diseases, has a very complex and complex pathogenesis, and ultimately, disorders of the immune system become important causes. However, laboratory methods for the immunological pathophysiology of HBV virus have not been fully developed compared to other research fields. Thus, the pathophysiological mechanisms of hepatitis B are still far from established. There are also few treatments that can help those who are infected.
석유황(石硫黃: sulfur)은 무기물 원소류강 비금속목에 속한 원소의 일종으로 천연산으로서 사방정계(斜方晶系)를 이루어 뾰족한 모양을 나타내며, 순수한 것은 엷은 황색 혹은 녹황색 내지 등적색을 띄며, 특이한 냄새가 있고 맛이 매우며 공기 중에 태우면 청색의 불꽃을 내며 이산화황의 자극성 냄새가 난다, 예로부터 항균작용 및 사하작용을 갖는 것으로 알려져 있다(대한약전외 한약규격집 주해서, 지형준, 이상인 저, 한국메디칼인덱스사 p216-217, 1988).Petroleum sulfur is a kind of element belonging to the mineral elemental steel nonmetallic tree. It is a natural acid and has a spiky shape. It is pale yellow or greenish yellow to light red. It has a peculiar smell, tastes great, and when burned in the air, it produces a blue flame and has an irritating odor of sulfur dioxide. It has been known to have antibacterial action and lowering action since ancient times. Medical Index Co. p216-217, 1988).
따라서 본 발명자는 자연계에 존재하는 여러 종의 광물생약 및 식물생약 등을 이용하여 항 HBV 바이러스 성분을 연구한 결과, 석유황을 함유한 복합생약조성물이 뛰어난 HBV 바이러스 증식 억제 효능을 나타냄을 확인하여, 새로운 간질환 치료용 조성물을 제공하고자 본 발명을 완성하였다.
Therefore, the present inventors studied anti-HBV virus components using various kinds of mineral herbals and plant herbs existing in nature, and found that the compound herbal composition containing petroleum sulfur exhibited an excellent effect of inhibiting HBV virus growth. The present invention was completed to provide a composition for treating liver disease.
본 발명의 목적은 항바이러스 활성을 갖는 석유황 및 유황을 함유한 조성물을 제공하는 것이다.
It is an object of the present invention to provide a composition containing petroleum sulfur and sulfur having antiviral activity.
상기 목적을 달성하기 위하여, 본 발명은 석유황 및 유황을 함유하는 간질환을 예방 및 치료하기 위한 약학 조성물을 제공한다.In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing and treating liver disease containing petroleum sulfur and sulfur.
상기한 간질환은 B형 간염바이러스에 의한 질환, 간염, 간경화 및 간암 등의 간질환을 포함한다.Such liver diseases include diseases caused by hepatitis B virus, liver diseases such as hepatitis, cirrhosis and liver cancer.
상기한 석유황 및 유황은 시중구입 가능한 것 및 그 용도에 따라 가공 또는 특수 처리한 것들을 포함한다.The petroleum sulfur and sulfur mentioned above include those commercially available and those processed or specially treated according to their use.
유황 또는 석유황은 통상적으로 원료 그대로를 섭취하게 되면 다소의 부작용을 유발할 수 있고 극소량만을 섭취할 수 있으므로 적정한 가공과정을 수행함이 바람직하다.Sulfur or petroleum sulfur is usually ingested as it is raw material may cause some side effects and can be consumed only a small amount, so it is desirable to perform the appropriate processing.
유황 또는 석유황은 시중에서 덩어리로 된 원재료와 기본적인 법제가 되어 있는 분말형태를 구입할 수 있는데 전자의 경우는 후자에 비해 오랜 기간동안의 법제과정이 필요하다.Sulfur or petroleum sulfur can be purchased commercially in the form of agglomerated raw materials and powder, which is a basic legislation. In the former case, a longer legal process is required than the latter.
또한, 본 발명에 사용될 수 있는 유황은, 예를 들어 가공처리하지 않은 유황을 일단 물에 담구어 풀어지게 한 후, 그 상태를 3~7일간 유지시켜 기본적인 독성을 제거한 다음, 건조시키고, 기타 법제에 쓰이는 약재분말과 함께 섞어 보관하여 사용할 수 있다. 이때 기타 약재의 비중은 1 내지 10% 정도로 한다. 침지시키는 물은 1일 내지 7일에 한번씩 교환할 수도 있으며, 약 10일간의 과정을 거쳐 사용 가능한 유황을 얻을 수 있다. In addition, the sulfur that can be used in the present invention, for example, after dissolving the untreated sulfur in water once to release it, the state is maintained for 3 to 7 days to remove the basic toxicity, then dried, and other legal It can be mixed and stored with the medicinal powder used in. At this time, the specific gravity of the other medicine is about 1 to 10%. The water to be immersed may be exchanged once every 1 to 7 days, and the available sulfur may be obtained through a process of about 10 days.
이와 같은 과정을 거쳐 의약품 또는 건강식품에 통상적으로 쓰일 수 있는 안전하고 다양한 형태의 조성물을 얻을 수 있다. Through this process it is possible to obtain a safe and various types of compositions that can be commonly used in medicine or health food.
상기의 제조방법으로 제조된 석유황은 B 형 간염 바이러스가 있는 혈청에 첨가하여 처리하였을 때 B 형 간염 바이러스의 증식을 억제하는 활성을 갖는다.The petroleum sulfur produced by the above production method has the activity of inhibiting the proliferation of hepatitis B virus when added to and treated with serum containing hepatitis B virus.
상기의 항바이러스 활성을 갖는 조성물은, 전체 조성물 총 중량에 대하여 상기 석유황 또는 유황을 0.01 내지 80%, 바람직하게는 1 내지 50% 중량비를 갖는 약학조성물을 제공한다.The composition having the antiviral activity provides a pharmaceutical composition having 0.01 to 80%, preferably 1 to 50% by weight of the petroleum sulfur or sulfur relative to the total weight of the total composition.
또한 상기 항바이러스 활성을 갖는 조성물은 간염, 간경화증 및 간암 등의 간질환의 치료에 사용할 수 있다.In addition, the composition having the antiviral activity can be used for the treatment of liver diseases such as hepatitis, cirrhosis and liver cancer.
본 발명의 석유황 또는 유황을 포함하는 조성물은 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다. Compositions containing petroleum sulfur or sulfur of the present invention may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.
본 발명의 석유황 또는 유황을 포함하는 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는, 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다.Carriers, excipients and diluents that may be included in the compositions comprising petroleum sulfur or sulfur of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin , Calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
본 발명의 석유황 또는 유황을 포함하는 항바이러스 활성을 갖는 조성물의 제제는 경고제, 과립제, 로션제, 리니멘트제(liniments), 리모나데제(limonades), 방향수제, 산제, 시럽제, 안연고제, 액제, 엑스제, 엘릭시르제(elixier), 연고제, 유당제, 유동엑스제, 에멀션제, 현탁제, 점안제, 정제, 좌제, 주사제, 주정제, 침제, 전제, 파스타제(pasta), 카타플라스마제(cataplasma), 캡슐제, 트로키제(troches), 팅크제(tincture) 또는 환제(丸劑)가 바람직하나, 상기 제제에 한정되지 않으며, 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다.Formulations of the composition having an antiviral activity comprising petroleum sulfur or sulfur of the present invention are warning agents, granules, lotions, liniments, limonades, fragrances, powders, syrups, ointments, Liquids, extracts, elixiers, ointments, lactose, liquid extracts, emulsions, suspensions, eye drops, tablets, suppositories, injections, spirits, dips, premises, pasta, cataplasma (cataplasma), capsules, troches, tinctures or pills are preferred, but are not limited to the above formulations and are formulated in the form of oral, external, suppository and sterile injectable solutions. Can be used.
본 발명의 상시 석유황 또는 유황을 함유하는 조성물은 목적하는 방법에 따라 비경구투여하거나 경구 투여할 수 있으며, 하루에 유효성분으로서 체중 1kg당 0.001 내지 10g, 바람직하게는 0.01 내지 5g의 양을 1 내지 수회에 나누어 음용할 수 있다. 특정인에 대한 음용용량 수준은 그 사람의 체중, 연령, 성별, 건강상태, 식이, 음용방법, 배설율, 증상의 중증도에 따라 변화 될 수 있으며, 상기 음용량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.Permanent petroleum sulfur or sulfur containing composition of the present invention can be parenterally administered or orally administered according to the desired method, the amount of 0.001 to 10g, preferably 0.01 to 5g per 1kg body weight as an active ingredient per day We can drink in several times. Drinking dose level for a particular person may vary depending on the person's weight, age, sex, health status, diet, drinking method, excretion rate, the severity of symptoms, the drinking dose limits the scope of the invention in any aspect It is not.
또한, 본 발명은 항바이러스 활성을 나타내는 석유황 또는 유황 및 식품학적으로 허용 가능한 식품보조첨가제를 포함하는 건강기능식품을 제공한다.The present invention also provides a dietary supplement comprising petroleum sulfur or sulfur exhibiting antiviral activity and a food supplement acceptable food supplement.
본 발명의 상기 석유황 또는 유황은 간질환 예방을 목적으로 식품 또는 음료에 첨가될 수 있다. 이 때, 식품 또는 음료 중의 상기 석유황 또는 유황의 양은, 일반적으로 본 발명의 건강 기능 식품 조성물은 전체 식품 중량의 0.01 내지 15 중량%로 가할 수 있으며, 건강 음료 조성물은 100 ㎖를 기준으로 0.01 내지 10 g, 바람직하게는 0.1 내지 1 g의 비율로 가할 수 있다. The petroleum sulfur or sulfur of the present invention may be added to food or beverage for the purpose of preventing liver disease. At this time, the amount of petroleum sulfur or sulfur in the food or beverage, in general, the functional food composition of the present invention can be added to 0.01 to 15% by weight of the total food weight, the health beverage composition is 0.01 to 10 based on 100 ml g, preferably 0.1 to 1 g.
본 발명의 건강 음료 조성물은 지시된 비율로 필수 성분으로서 상기 석유황 또는 유황을 함유하는 외에는 액체성분에는 특별한 제한점은 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 ㎖당 일반적으로 약 1 내지 20g, 바람직하게는 약 5 내지 12g이다.The health beverage composition of the present invention has no particular limitation on the liquid component except for containing the petroleum sulfur or sulfur as essential components in the indicated ratios, and may contain various flavors or natural carbohydrates as additional components, such as ordinary drinks. . Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of natural carbohydrates is generally about 1-20 g, preferably about 5-12 g per 100 ml of the composition of the present invention.
상기 외에 본 발명의 조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명의 조성물들은 천연 과일 쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid and its Salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. The compositions of the present invention may also contain pulp for the production of natural fruit juices and fruit juice beverages and vegetable beverages. These components can be used independently or in combination. The proportion of such additives is not so critical but is generally selected from the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.
이하, 본 발명을 실시예에 의해 상세히 설명한다.Hereinafter, the present invention will be described in detail by way of examples.
단, 하기 실시예 및 실험예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실시예 및 실험예에 한정되는 것은 아니다.
However, the following Examples and Experimental Examples are only illustrative of the present invention, and the content of the present invention is not limited to the following Examples and Experimental Examples.
실시예 1. 석유황 분말의 제조예 1Example 1 Preparation Example 1 of Petroleum Sulfur Powder
석유황 200g을 물에 넣어 7일간 침지시킨 후, 건조기로 건조시키고 분말화하여 사용하였다. 침지시키는 물은 2일에 한번씩 교환하였다. 실험에 사용시 PBS에 녹여 멸균하여 사용하였다.
200 g of petroleum sulfur was immersed in water for 7 days, and then dried in a dryer and powdered. The water to be immersed was changed every 2 days. When used in the experiment was dissolved in PBS sterilized.
실시예 2. 석유황 및 유황 혼합분말의 제조예 2Example 2 Preparation Example 2 of Mixed Petroleum Sulfur and Sulfur Powder
석유황 100g을 물에 넣어 5일간 침지시키고, 건조기로 건조한 후에 이를 분말화하였다. 또한 유황 100g을 물에 넣어 5일간 침지시키고 건조, 분말화하여, 상기 제조된 석유황과 혼합기로 균일하게 혼합한 후에 여기에 100ml의 증류수를 가하여 반죽기로 골고루 반죽한 후에 이를 건조시켜 분말 200g을 얻었다. 실험에 사용시 PBS에 녹여 멸균하여 사용하였다.
100 g of petroleum sulfur was immersed in water for 5 days, dried in a dryer, and powdered. In addition, 100g of sulfur was immersed in water for 5 days, dried and powdered, uniformly mixed with the petroleum sulfur prepared above with a mixer, and then 100ml of distilled water was added thereto, and kneaded evenly with a kneader, and dried to obtain 200g of powder. When used in the experiment was dissolved in PBS sterilized.
실험예 1. HBV 바이러스 DNA 억제 실험Experimental Example 1. HBV virus DNA inhibition experiment
본 발명의 실시예 1 및 2 분말의 HBV 바이러스의 DNA에 대한 억제능을 측정하기 위하여, 마이크로플레이트 상에서 화학발광법을 이용하여 혈청 내에 존재하는 B형 감염 바이러스의 DNA를 정량검사하였다. In order to measure the inhibitory ability of HBV virus against DNA of the powders of Examples 1 and 2 of the present invention, the DNA of hepatitis B virus present in serum was quantitated by chemiluminescence on a microplate.
상기 실험은 혈청 내에 포함되어 있는 HBV 바이러스의 DNA와 결합할 수 있는 RNA 탐색자(RNA probe, ad & av stralms)를 이용하여 DNA:RNA 하이브리드를 만든 후, 이에 특이적인 항체가 포함되어 있는 마이크로플레이트에 포획(Capture)하고, 포획된 하이브리드를 알카린 포스파타제가 컨쥬게이션된 항체와 결합시킨 후, 이를 화학발광물질을 사용하여 혈청 내에 존재하는 HBV바이러스의 DNA의 양을 빛의 세기로 측정하고 표준곡선 (calibration curve)을 통해 그 농도를 결정하는 방법으로, 상기 실험을 위하여 하이브리드 캡쳐 HBV DNA 테스트 키트(Hybrid capture II HBV DNA test kit, Digene사제)를 사용하였다.The experiment was performed by using RNA probes (RNA probes, ad & av stralms) capable of binding to DNA of the HBV virus contained in the serum, and then making a DNA: RNA hybrid to a microplate containing specific antibodies thereto. After capturing and binding the captured hybrid to an antibody conjugated with alkaline phosphatase, the chemiluminescent material is used to measure the amount of DNA of the HBV virus present in the serum by light intensity and the standard curve ( As a method of determining the concentration through a calibration curve, a hybrid capture II HBV DNA test kit (manufactured by Digene) was used for the experiment.
상기 실험은 11명의 B형 감염 환자의 혈청을 가지고 실험하였으며, 활동 바이러스성 B형 감염 환자 혈청 중의 HBV 바이러스(국립보건원 소화기계바이러스과, 2002년 10월 18일 입수) DNA(실험군 S) 및 활동 바이러스성 B형 간염 환자 혈청에 PBS 용액으로 희석시킨 실시예 1의 석유황 용액(500㎍/㎖)을 처리하여 37℃에서 2시간 및 8시간동안 반응시킨 후 혈청 중의 HBV 바이러스 DNA(실험군 A)의 양을 비교하여 본 발명의 석유황 함유 조성물의 HBV 바이러스 DNA 억제효과를 확인하였다.
The experiment was performed with sera from 11 patients with type B infection, HBV virus (National Institute of Gastrointestinal Tract Virus, October 18, 2002) DNA and active virus in the sera of patients with active viral type B infection. The amount of HBV virus DNA (Experimental Group A) in serum after treatment with the petroleum sulfur solution (500 µg / ml) of Example 1 diluted with PBS solution to serum for hepatitis B patients for 2 hours and 8 hours at 37 ° C Comparison was made to confirm the HBV virus DNA inhibitory effect of the petroleum sulfur-containing composition of the present invention.
1-1. 대조군 및 실험군1-1. Control and experimental groups
칼리브레이터 1(Cal 1)은 HBV 음성의 인간 혈청내 운반체 DNA와 소듐 아지드를, 칼리브레이터 2(Cal 2)는 HBV 음성의 인간 혈청내 1.42×105 copies/㎖ (5pg/㎖) HBV 바이러스 플라스미드 DNA 와 운반체 DNA 및 소듐 아지드를, 칼리브레이터 3(Cal 3)는 HBV 음성의 인간 혈청내 2.83×107 copies/㎖ (100pg/㎖) HBV 바이러스 플라스미드 DNA 와 운반체 DNA 및 소듐 아지드를, 칼리브레이터 4(Cal 4)는 HBV 음성의 인간 혈청내 5.66×108 copies/㎖ (2000pg/㎖) HBV 바이러스 플라스미드 DNA 와 운반체 DNA 및 소듐 아지드를, 칼리브레이터 5(Cal 5)는 HBV 음성의 인간 혈청 내 1.70×109 copies/㎖ (6000pg/㎖) HBV 바이러스 플라스미드 DNA 와 운반체 DNA 및 소듐 아지드를 포함한다.Calibrator 1 (Cal 1) is the carrier DNA and sodium azide in HBV negative human serum, Calibrator 2 (Cal 2) is 1.42 × 10 5 copies / ml ( 5 pg / ml) in HBV negative human serum. HBV virus plasmid DNA with carrier DNA and sodium azide, Calibrator 3 (Cal 3) is 2.83 × 10 7 copies / ml (100 pg / ml) HBV virus plasmid DNA with HBV negative human serum and carrier DNA and sodium azide. Zide, Calibrator 4 (Cal 4), contains 5.66 × 10 8 copies / ml (2000 pg / ml) HBV virus plasmid DNA and carrier DNA and sodium azide in HBV-negative human serum. ) Contains 1.70 × 10 9 copies / ml (6000 pg / ml) HBV virus plasmid DNA in HBV negative human serum and carrier DNA and sodium azide.
음성대조군으로서 C2군은 HBV를 함유한 간염환자 혈청을 PBS와 혼합하여 37℃에서 2시간 방치한 것이고, C4군은 8시간 방치한 것이다.As a negative control group, the C2 group was mixed with PBS for hepatitis serum containing HBV and left at 37 ° C. for 2 hours, and the C4 group was left for 8 hours.
양성대조군으로서 Z2군은 HBV를 함유한 간염환자 혈청을 제픽스(라미뷰딘 1mg/ml)와 혼합하여 37℃에서 2시간 방치한 것이고, Z4군은 8시간 방치한 것이다.As a positive control group, Z2 group was mixed with HBV-containing hepatitis serum and zepix (ramimidine 1mg / ml) and left at 37 ° C for 2 hours, and Z4 group was left for 8 hours.
실험군 S는 활동바이러스성 B형 감염환자 혈청 20㎕에 PBS 10㎕를 처리한 것이며, 실험군 A는 활동바이러스성 B형 감염환자 혈청 20㎕에 실험예 2의 복합생약 용액(농도: 50g/1.5ℓ) 10㎕ 처리한 것이다.Experimental group S was treated with 10 µl of PBS in 20 µl of active viral type B infected patients, and experimental group A was treated with 20 µl of active viral type B infected patients with a mixed herbal solution of Experimental Example 2 (concentration: 50 g / 1.5 l). ) 10 μl.
1-2. HBV가 있는 혈청에 대한 시료 처리1-2. Sample Processing for Serum with HBV
먼저 65℃로 온도를 미리 맞추어 놓았던 마이크로플레이트 히터(microplate heater)에서 마이크로플레이트를 꺼낸 후 즉시 실러(sealer)를 제거하고, 검체를 미리 10- 15초간 볼텍싱하고 분주시 벽면과의 접촉을 피하면서 기포가 생기지 않도록 주의하면서, 칼리브레이터(Calibrators; Cal 1, Cal 2 각 3개, Cal 3, Cal 4 및 Cal 5 각 2개), 대조군(P3 및 P2), 실험군(실험군 S 및 실험군 A)을 각각 마이크로플레이트 각각 30㎕씩(HBV 양성 혈청 20㎕ 및 PBS 희석약제 10㎕) 분주하고, 대조군도 30㎕씩 (HBV 양성 혈청 20㎕ 및 PBS 10㎕)을 분주하였다.First remove the microplate from the microplate heater, which was previously set at 65 ° C, then immediately remove the sealer, vortex the sample for 10-15 seconds in advance and avoid contact with the wall during dispensing. Calibrators; 3 each of
마이크로플레이트 실러를 이용하여 마이크로플레이트를 덮고 37℃에서 120분간 배양시켰다. The microplate was covered using a microplate sealer and incubated at 37 ° C. for 120 minutes.
1-3. 변성 (Denaturation)1-3. Denaturation
변성 시약병(denaturation reagent bottle)에 지시염료(indicator dye)를 한 방울 넣고 섞은 후, 상기 1-1의 마이크로플레이트의 각 웰에 변성시약을 30㎕씩 분주하였다. 그 다음 실러로 웰을 덮은 후, 1분 동안 1100±100rpm으로 흔들어 혼합하였다. 이때 자색으로 용액이 변하였고, 65±2℃의 히터에서 30±3분 동안 반응시켰다.One drop of an indicator dye was added to a denaturation reagent bottle, and then 30 μl of a denaturing reagent was dispensed into each well of the microplate of 1-1. The wells were then covered with a sealer and mixed by shaking at 1100 ± 100 rpm for 1 minute. At this time, the solution was changed to purple, and reacted for 30 ± 3 minutes in a heater of 65 ± 2 ℃.
1-4. 탐침자 혼합액(Probe mixture) 준비1-4. Probe mixture preparation
하이브리드 캡쳐 키트 내의 HBV 탐침자가 든 시약병을 3-5초간 원심분리한 후, 탐침자 희석액 6.0㎖에 240㎕를 완전히 섞어 탐침자 혼합액을 준비하였다.After centrifuging the reagent bottle containing the HBV probe in the hybrid capture kit for 3-5 seconds, the probe mixture was prepared by thoroughly mixing 240 µl in 6.0 ml of the diluent of the probe.
1-5. 혼성화반응(Hybridization)1-5. Hybridization
상기 실험예 1-1의 마이크로플레이트의 실러를 제거하고 상기 실험예 1-3의 탐침자 혼합액을 30㎕씩 분주한 후 플레이트를 실러로 다시 덮고 1분동안 1100±100rpm으로 흔들어 혼합하였다. 이때 노란색으로 용액의 색깔이 변하게 되었고, 다시 65±2℃의 히터에서 30±3분 동안 반응시켰다.The sealer of the microplate of Experimental Example 1-1 was removed, and 30 µl of the probe mixture of Experimental Example 1-3 was dispensed, and the plate was again covered with a sealer and mixed by shaking at 1100 ± 100 rpm for 1 minute. At this time, the color of the solution was changed to yellow, and reacted again for 30 ± 3 minutes in a heater of 65 ± 2 ℃.
1-6. 하이브리드 캡쳐 반응 (Hybrid Capture reaction)1-6. Hybrid capture reaction
상기 1-4의 플레이트를 꺼낸 후, 캘리브레이터, 대조군, 약물처리한 검체들을 각각 캡쳐 마이크로플레이트(DIGENE사)로 75㎕씩 각 웰에 옮긴 후, 실러로 캡쳐 마이크로플레이트를 덮고 18 내지 25℃에서 60±5분간 1100±100rpm으로 흔들어 반응시켰다. 반응 후, 캡쳐 마이크로플레이트의 여액을 파이펫으로 제거한 후, 다시 2 내지 3 회 흡수지에 두들겨서 여액을 완전히 제거하였다. After removing the plates 1-4, the calibrator, the control, and the drug-treated samples were transferred to each well by 75 µl with a capture microplate (DIGENE), and then covered with a sealer and the capture microplate was 60 at 18 to 25 ° C. The reaction was shaken at 1100 ± 100 rpm for ± 5 minutes. After the reaction, the filtrate of the capture microplate was removed with a pipette and then beaten again on a blotting paper two or three times to completely remove the filtrate.
1-7. 하이브리드 캡쳐 탐색 (Hybrid Capture detection)1-7. Hybrid capture detection
소듐 아지드(sodium azide)를 포함하는 완충용액 중에서 알카린 포스파타제(alkaline phosphatase)가 컨쥬게이션된, RNA:DNA 하이브리드에 대한항체를 반응시킨 검출시약(키트내 탐색시약 1) 75㎕를 각각의 캡처 마이크로플레이트 웰에 분주하고, 마이크로플레이트 실러를 이용하여 캡처 마이크로플레이트 웰을 덮고 20~25℃에서 30분간 배양하였다. 이후 캡처 마이크로플레이트 웰의 여액을 완전히 제거한 후 캡처 마이크로플레이트 웰을 소듐아지드를 포함하는 회석세척액으로 넘치도록 채운 후 뒤집어서 버리는 방식으로 6회 세척하였다. Capture 75 μL of each reagent in the buffer containing sodium azide to which the antibody was reacted with an RNA: DNA hybrid conjugated with alkaline phosphatase (
1-8. 시그날 증폭 (Signal amplification)1-8. Signal amplification
세척한 캡처 플레이트를 깨끗한 흡수지 위에서 10 내지 15분정도 뒤집어 방치하여 남은 여액을 흡수시킨 후, 각각의 캡처 마이크로플레이트 웰에 화학발광물질(CDP-StarTM, Chemilumlnescent substrate, 키트 내 탐색시약 2)을 75㎕씩 분주하였다. 마이크로플레이트 실러를 이용하여 캡처 마이크로플레이트 웰을 덮고 실온에서 15분 동안 직사광선을 피하여 배양하였다. 반응이 끝난 후 15분 이내에 DML 2000 루미노미터 (Luminometer, DIGENE사)를 이용하여 혈청 내에 존재하는 HBV 바이러스의 DNA 양을 빛의 세기로 측정하였다.The washed capture plate was left inverted for 10-15 minutes on a clean blotter paper to absorb the remaining filtrate, and each capture microplate well was filled with a chemiluminescent material (CDP-Star ™ , Chemilumlnescent substrate,
실험에서, P3 및 P2 (양성대조군)는 감염성 HBV 바이러스 및 소듐 아지드를 포함한다.
In the experiments, P 3 and P 2 (positive control) included infectious HBV virus and sodium azide.
1-9. 결과1-9. result
음성대조군으로서 C군은 HBV를 함유한 간염환자 혈청을 PBS와 혼합하여 37℃에서 2시간 방치한 것과 8시간 방치한 것이다.Group C, a negative control group, was mixed with PBS for hepatitis serum containing HBV and left at 37 ° C. for 2 hours and for 8 hours.
양성대조군으로서 Z군은 HBV를 함유한 간염환자 혈청을 제픽스(라미뷰딘 1mg/ml)와 혼합하여 37℃에서 2시간 방치한 것과 8시간 방치한 것이다.As a positive control group, Z group was mixed with HBV-containing hepatitis serum and zepix (ramimidine 1mg / ml) and left for 2 hours at 37 ° C for 8 hours.
실험군 S는 활동바이러스성 B형 감염환자 혈청 20㎕에 PBS 10㎕를 처리한 것이며, 실험군 A는 활동바이러스성 B형 감염환자 혈청 20㎕에 실험예 2의 복합생약 용액(농도: 50g/1.5ℓ) 10㎕ 처리한 것이다. Experimental group S was treated with 10 µl of PBS in 20 µl of active viral type B infected patients, and experimental group A was treated with 20 µl of active viral type B infected patients with a mixed herbal solution of Experimental Example 2 (concentration: 50 g / 1.5 l). ) 10 μl.
하기 표 1의 결과를 보면, 복합생약을 처리한 실험군 A에서의 HBV DNA의 양이 실험군 C 및 Z보다 감소되어 HBV 바이러스를 억제함을 확인하였다.Looking at the results of Table 1, it was confirmed that the amount of HBV DNA in the experimental group A treated with the compound herbal was reduced than the experimental groups C and Z to inhibit the HBV virus.
또한, 표 2의 결과를 보면, 환자 11명의 혈청에 본 발명의 조성물을 처리한 경우, 9명의 혈청에서 PBS 처리시보다 HBV 바이러스 DNA가 현저히 감소되어, 본 발명의 조성물이 HBV 바이러스 증식억제에 효과가 있음을 확인하였다.
In addition, the results of Table 2 show that when the composition of the present invention was treated with the sera of 11 patients, the HBV virus DNA was significantly reduced compared to the PBS treatment with 9 sera, and the composition of the present invention was effective in inhibiting HBV virus growth It was confirmed that there is.
표 1, 표 2 및 도 1로부터, 본 발명의 조성물이 HBV 바이러스 DNA 억제하는데 유효함을 알 수 있다.
From Table 1, Table 2 and Figure 1, it can be seen that the composition of the present invention is effective for inhibiting HBV viral DNA.
실험예 2. 독성 실험Experimental Example 2. Toxicity Test
본 발명의 석유황의 독성을 시험하기 위하여, 동물실험을 수행하였다.In order to test the toxicity of the petroleum sulfur of the present invention, animal experiments were performed.
25±5g의 ICR계 마우스(중앙실험동물)와 235±10g의 특정병원부재(SPF) 스프라그-도올리(Sprague Dawley, Biogenomics사) 래트를 각각 3마리씩 3군으로 나누어 본 발명의 석유황(실시예 1) 각각 20mg/㎏, 10mg/㎏, 1mg/㎏의 용량으로 복강투여한 후 24시간 동안 독성여부를 관찰하였다.The petroleum sulfur of the present invention was divided into three groups of 25 ± 5g of ICR mice (central laboratory animals) and 235 ± 10g of SPF Sprague Dawley (Biogenomics) rats. Example 1) Toxicity was observed for 24 hours after intraperitoneal administration at 20 mg / kg, 10 mg / kg and 1 mg / kg, respectively.
실험 결과, 3군 모두에서 사망한 예를 전혀 관찰할 수 없었고, 체중 증가, 사료 섭취량 등에서 외견상 대조군과 별다른 증상을 찾아볼 수 없었다. 따라서 본 발명의 석유황이 안전한 약물임을 확인할 수 있었다.
As a result, no deaths were observed in all three groups, and no significant symptoms were found in weight gain and feed intake. Therefore, it could be confirmed that petroleum sulfur of the present invention is a safe drug.
임상예 1. 간경변치유효과Clinical Example 1. Hepatic Cirrhosis Effect
56세의 중국인 남자환자 유 **의 경우 2000년 B형 간염, 간경변, 간암 3기로 판정(중국 상해시 폐과병원 흉부외과, 도 2a 참조)되었으나, 2000년 6월 2일부터 본 발명의 석유황 함유 조성물을 1회에 석유황 1g 씩, 식후 1일 3회 10개월 복용한 결과, 2001년 4월 18일 CT 검사결과(도 2b 참조) 간경변 현상이 소실되었고, 간기능이 정상으로 회복됨을 확인하였다.
The 56-year-old Chinese male patient ** was determined to have three hepatitis B, cirrhosis, and liver cancer in 2000 (see Pulmonary Surgery, Lung Hospital, Shanghai, China, see FIG. 2A). 1g of petroleum sulfur at a time, three times a day after meals for 10 months, CT scan results on April 18, 2001 (see Fig. 2b) was confirmed that the liver cirrhosis disappeared, and the liver function is restored to normal.
임상예 2. 간기능 회복효과Clinical Example 2. Liver Function Restoration Effect
60세의 한국인 남자환자 허** 는 만성활동성 간염으로 서울대학병원 내과로부터 제픽스(라미부딘)를 3년 동안 복용해 오던 중 부작용으로 제픽스 복용을 중단 하였고 GOT, GPT 수치가 600-1000으로 급상승하였으나, 본 발명의 석유황 함유 조성물을 1회에 석유황 1g 씩, 식후 1일 3회 2주간 복용한 결과 GOT 수치는 49, GPT 수치는 35로 거의 간기능이 정상으로 돌아온 것을 확인하였다(표 3 참조).
A 60-year-old Korean male, Huh, who had been taking Gepix (Lamivudine) from Seoul National University Hospital for three years because of chronic active hepatitis, stopped taking Gepix due to side effects, and the GOT and GPT levels soared to 600-1000. When the petroleum sulfur-containing composition of the present invention was taken 1 g of petroleum sulfur at a time, two times three times a day after a meal, the GOT value was 49 and the GPT value was 35, and it was confirmed that the liver function was almost returned to normal (see Table 3).
본 발명의 석유황은 아래와 같은 제형으로 투여할 수 있으며, 아래의 제제 실시예는 본 발명을 예시하는 것일 뿐, 이에 의해 본 발명의 내용이 제한되는 것은 아니다. Petroleum sulfur of the present invention can be administered in the following formulations, the formulation examples below are merely to illustrate the invention, whereby the content of the invention is not limited.
하기의 상기 약학적 제제의 제제예를 설명하나, 이는 본 발명을 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.
Hereinafter, the formulation examples of the pharmaceutical preparations will be described, which are intended to explain in detail only, not to limit the present invention.
제제예 1. 주사제제의 제조Formulation Example 1 Preparation of Injection
실시예 1의 석유황............................1.0㎎Petroleum sulfur of Example 1 ...... 1.0 mg
소디움 메타비설파이트........................3.0㎎Sodium metabisulfite ........ 3.0mg
메틸파라벤...................................0.8㎎Methylparaben ............... 0.8 mg
프로필파라벤.................................0.1㎎Propylparaben ...................... 0.1 mg
주사용 멸균증류수...........................적량Sterile distilled water for injection ..............
상기의 성분을 혼합하고 통상의 방법으로 2㎖로 한 후, 2㎖ 용량의 앰플에 충전하고 멸균하여 주사제를 제조한다.
The above ingredients are mixed and made into 2 ml by a conventional method, and then filled into 2 ml ampoules and sterilized to prepare an injection.
제제예 2. 정제의 제조Formulation Example 2 Preparation of Tablet
실시예 1의 석유황.............................20㎎Petroleum sulfur of Example 1 ... 20 mg
유당........................................100㎎Lactose 100 mg
전분........................................100㎎Starch .............................. 100 mg
스테아린산 마그네슘.........................적량Magnesium Stearate ...............
상기의 성분을 혼합하고 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조한다.
The above components are mixed and tableted according to a conventional method for producing tablets to produce tablets.
제제예 3. 캡슐제의 제조Formulation Example 3 Preparation of Capsule
실시예 1의 석유황............................10㎎Petroleum sulfur of Example 1 ... 10 mg
유당........................................50㎎Lactose 50 mg
전분........................................50㎎Starch ........................................ 50 mg
탈크........................................2㎎Talc ........................................ 2mg
스테아린산마그네슘......................... 적량Magnesium Stearate ...............
상기의 성분을 혼합하고 통상의 캡슐제의 제조방법에 따라서 젤라틴 캡슐에 충전하여 캡슐제를 제조한다.
Capsules are prepared by mixing the above ingredients and filling into gelatin capsules according to a conventional method for preparing capsules.
제제예 4. 액제의 제조Formulation Example 4 Preparation of Liquid
실시예 1의 석유황............................100㎎Petroleum sulfur of Example 1 ... 100 mg
설탕........................................20ｇSugar .................................. 20g
이성화당....................................20ｇIsomerized sugar ......................................... 20 g
레몬향......................................적량Lemon Flavor ......................
정제수를 가하여 전체........................100㎖Purified water is added to the whole ........... 100ml
상기의 성분을 통상의 액제의 제조방법에 따라서 혼합하고 100㎖의 갈색병에 충전하고 멸균시켜서 액제를 제조한다.
The above components are mixed according to a conventional method for preparing a liquid, filled into a 100 ml brown bottle, and sterilized to prepare a liquid.
제제예 5. 건강 식품의 제조Formulation Example 5 Preparation of Healthy Food
실시예 1의 석유황...........................1000 ㎎ Petroleum sulfur of Example 1 ... 1000 mg
비타민 혼합물..............................적량Vitamin Blend ........................
비타민 A 아세테이트...............70 ㎍Vitamin A Acetate ............... 70 μg
비타민 E..........................1.0 ㎎Vitamin E ........... 1.0 mg
비타민 B1.........................0.13 ㎎Vitamin B1 ......... 0.13 mg
비타민 B2.........................0.15 ㎎Vitamin B2 ........... 0.15 mg
비타민 B6.........................0.5 ㎎Vitamin B6 ............ 0.5 mg
비타민 B12........................0.2 ㎍Vitamin B12 ........................ 0.2 μg
비타민 C..........................10 ㎎Vitamin C ......................................... 10 mg
비오틴............................10 ㎍Biotin ............... 10 μg
니코틴산아미드....................1.7 ㎎Nicotinic Acid Amide ... 1.7 mg
엽산..............................50 ㎍Folic acid ............... 50 ㎍
판토텐산 칼슘.....................0.5 ㎎Calcium Pantothenate ..................... 0.5 mg
무기질 혼합물...............................적량Inorganic mixtures ...............
황산제1철.........................1.75 ㎎Ferrous Sulfate ............... 1.75 mg
산화아연..........................0.82 ㎎Zinc Oxide ........... 0.82 mg
탄산마그네슘......................25.3 ㎎Magnesium Carbonate ......... 25.3 mg
제1인산칼륨.......................15 ㎎Potassium monophosphate ......................................... 15 mg
제2인산칼슘.......................55 ㎎Dicalcium Phosphate ............... 55 mg
구연산칼륨........................90 ㎎Potassium citrate ... 90 mg
탄산칼슘..........................100 ㎎ Calcium Carbonate ... 100 mg
염화마그네슘......................24.8 ㎎Magnesium Chloride ............... 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강식품 조성물 제조에 사용할 수 있다.
Although the composition ratio of the above-mentioned vitamin and mineral mixtures is mixed with a component suitable for a health food in a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method. The granules may be prepared and used for preparing a health food composition according to a conventional method.
제제예 6. 건강 음료의 제조Formulation Example 6 Preparation of Healthy Drink
실시예 1의 석유황..............................1000 ㎎Petroleum sulfur of Example 1 ..... 1000 mg
구연산........................................1000 ㎎Citric Acid ........................................ 1000 mg
올리고당......................................100 gOligosaccharide ......................... 100 g
매실농축액.....................................2 gPlum concentrate ........................... 2 g
타우린.........................................1 gTaurine ......................................... 1 g
정제수를 가하여..............................전체 900 ㎖Purified water is added ............................................. 900 ml
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간동안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2ℓ 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강음료 조성물 제조에 사용한다. After mixing the above components in accordance with a conventional healthy beverage production method, and stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed sterilization and then refrigerated and stored in the present invention For the preparation of healthy beverage compositions.
상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 수요계층, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.
Although the composition ratio is a composition that is relatively suitable for the preferred beverage in a preferred embodiment, the compounding ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.
본 발명이 제공하는 백반 및 석유황을 포함하는 복합생약은 HBV 바이러스 증식을 억제하는 효과가 뛰어나므로 간질환 치료활성을 갖는 조성물로서 의약품 및 건강기능식품에 사용할 수 있다.
Complex herbal medicine containing alum and petroleum sulfur provided by the present invention is excellent in inhibiting HBV virus proliferation, and thus can be used in pharmaceuticals and health functional foods as a composition having therapeutic activity for liver disease.
Claims (5)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020030056650A KR100861677B1 (en) | 2003-08-14 | 2003-08-14 | Composition comprising sulfur for treatment and prevention of liver disease |
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| Application Number | Priority Date | Filing Date | Title |
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| KR1020030056650A KR100861677B1 (en) | 2003-08-14 | 2003-08-14 | Composition comprising sulfur for treatment and prevention of liver disease |
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| KR20050019950A KR20050019950A (en) | 2005-03-04 |
| KR100861677B1 true KR100861677B1 (en) | 2008-10-06 |
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| KR1020030056650A KR100861677B1 (en) | 2003-08-14 | 2003-08-14 | Composition comprising sulfur for treatment and prevention of liver disease |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101393598B1 (en) | 2013-07-17 | 2014-05-09 | 임춘규 | Healthy food composition for healing a hangover |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01156916A (en) * | 1987-09-25 | 1989-06-20 | Ss Pharmaceut Co Ltd | Remedy for hepatic disease |
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2003
- 2003-08-14 KR KR1020030056650A patent/KR100861677B1/en not_active IP Right Cessation
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01156916A (en) * | 1987-09-25 | 1989-06-20 | Ss Pharmaceut Co Ltd | Remedy for hepatic disease |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101393598B1 (en) | 2013-07-17 | 2014-05-09 | 임춘규 | Healthy food composition for healing a hangover |
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