KR20020091641A - Pharmaceutical composition comprising a swellfish extract for anticancer therapy - Google Patents
Pharmaceutical composition comprising a swellfish extract for anticancer therapy Download PDFInfo
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Abstract
Description
본 발명은 복어 추출액을 함유하는 항암 치료용 약학 조성물에 관한 것으로서 특히, 복어알의 수성 추출액을 이용하여 유방암, 위암, 예암, 간암, 난소암 등 다양한 암을 치료할 수 있는 약학 조정물에 관한 것이다.The present invention relates to a pharmaceutical composition for treating anticancer containing blowfish extract, and more particularly, to a pharmaceutical modifier capable of treating various cancers such as breast cancer, stomach cancer, chemo, liver cancer, and ovarian cancer using an aqueous extract of puffer fish.
일반적으로, 복어에는 테트로도톡신(Tetrodotoxin)이라고 불리우는 독성이 강한 성분이 함유되어 있다는 것이 오랫동안 알려져 왔다. 복어 독의 주요 기원은 궁반동방돈(활무늬 반점이 있는 복어), 충문동방돈(벌래무늬가 있는 복어) 및 암색동방돈의 고환, 난소, 간장, 비장, 안구 및 혈액으로서, '독약본초'에는 복어 독이 온하며 대독 즉, 극독하며 진통, 항심율실상, 혈압강하 등을 치료하고 문등병으로 인한 동통과 뇨포피염(尿布皮炎)을 치료하는 효능이 있다고 적혀있다. 복어 독의 화학적 성분은 극독성의 비단백 신경독소로서, 그 구조는 일종의 아미노산수산퀴놀린형의 화합물이다.In general, it has long been known that puffer fish contains a highly toxic ingredient called Tetrodotoxin. The main origins of the pufferfish poison are the testicular, ovary, soy, spleen, eyeballs and blood of the tongbangdon (livefish with lively spots), the Chungmundongdon (fishfish with swelling) and the dark Eastern piglet. It is said that pufferfish poison is warm, and it is effective to treat severe poisoning, that is, extreme pain, anorexia nervosa, blood pressure lowering, and pain caused by leprosy, and urinary bleeding (尿布 皮炎). The chemical component of the blowfish poison is a highly toxic nonprotein neurotoxin, the structure of which is a compound of the amino acid quinoline type.
복어 독의 약리 작용은 「독약 본초」등에 기록되어 있을 뿐 아니라 많은 연구가 이루어져 있는 바, 복어 독의 대표적인 약리 작용으로서 다음과 같은 것들이 알려져 있다.The pharmacological action of pufferfish poison is not only recorded in the poisonous herb, but also many studies have been conducted.
첫째, 세포막의 나트륨 통로에 관한 영향으로서 복어독은 고선택성과 소친화성으로 신경흥분막에서의 나트륨 미립자의 통로를 차단시킴으로써 그 독성을 나타내는 것으로 알려져 있다.First, as an effect on the sodium channel of the cell membrane, blowfish poison is known to exhibit its toxicity by blocking the passage of sodium microparticles in the neural excitable membrane with high selectivity and small affinity.
둘째, 세포분열에 대한 영향으로서 복어 독은 작은 쥐의 골수세포미핵 및 분열지수의 산생에 현저한 영향을 주며 장춘(長春)(Vincristine Siltate, Vincristine. Leurocristine. On-cavin. Vcr. Nsc-67574. Lcr. Leucicl. Kyocristine)과 비교하면 미핵지표상에서는 장춘의 수준에 달하지 못하지만 분열지수상으로는 장춘을 능가하는 효과가 있어서 비교적 강한 세포유사분열을 억제하는 중독제 혹은 억제제이다.Second, as an effect on cell division, blowfish poison has a significant effect on the production of myelocytic nuclei and cleavage index of small rats, and it is known as Vincristine Siltate, Vincristine. Leurocristine.On-cavin.Vcr.Nsc-67574.Lcr Compared with Leucicl.Kyocristine), it is an addict or inhibitor that inhibits relatively strong cell-like division because it does not reach the level of Changchun on the US nuclear indicator, but it exceeds the Changchun on the division index.
셋째, 진통 효과에 관한 것으로 복어 간 중에서 증류시켜 뽑아낸 복어 독산(酸) 주사액은 그 진통 효과가 모르핀, 두령정(杜令丁, Pethidine Hyclrochoride)의 진통 효과에 상당하여 둔통이나 예통에 대하여 완화 작용을 할 수 있다.Thirdly, it relates to analgesic effect. Pufferfish toxic acid extract extracted from the puffer fish liver has the analgesic effect corresponding to the analgesic effect of morphine and durinjeong (pethidine hyclrochoride). can do.
이외에도 복어 독은 국소마취약과 함께 사용하였을 때 마취시간을 연장시키는 작용, 심혈관계에 관한 작용 등이 알려져 있다.In addition, blowfish poison is known to prolong the anesthesia time when used with local anesthetics, to work on the cardiovascular system.
본 발명은 상기와 같이 복어 독에 관하여 알려진 약리 작용 중 세포분열을 억제하는 작용이 있다는 점에 착안하여 복어 독 성분을 함유하는 추출액을 제조하여 세포의 이상 증식으로 인한 암의 치료에 사용될 수 있는 복어 추출액을 함유하는 항암 치료용 약학 조성물을 제공하는데 그 목적이 있다.The present invention focuses on the fact that there is an action of inhibiting cell division among known pharmacological actions related to blowfish poison as described above. An object of the present invention is to provide an anticancer pharmaceutical composition containing an extract.
본 발명의 다른 목적은 복어 추출액을 사용하여 암 환자의 통증을 제어하는 것이다.Another object of the present invention is to control the pain of cancer patients using blowfish extract.
도 1은 래트 1차 배양 정상 간 세포에 대한 복어 추출액의 세포분열 억제 효과 실험 결과 그래프,1 is a graph showing the results of inhibition of cell division of blowfish extract on rat primary cultured normal liver cells;
도 2는 마우스 정상 비장 세포에 대한 복어 추출액의 세포분열 억제 효과 실험 결과 그래프,2 is a graph showing the results of cell division inhibition effect experiment of puffer fish extract on mouse normal spleen cells
도 3은 간 암세포에 대한 복어 추출액의 세포분열 억제 효과 실험 결과 그래프이다.Figure 3 is a graph showing the results of cell division inhibitory effect of the blowfish extract on liver cancer cells.
상기와 같은 목적을 달성하기 위하여 본 발명은, 복어 추출액을 활성성분으로 함유하고 약학적으로 허용되는 첨가제를 함유하는 항암치료용 약학 조성물로서, 활성성분은 상기 복어 추출액 외에 항암제로 공지된 5-플루오로우라실, 메토트렉세이트, 아드리아마이신, 탁솔로 이루어진 군에서 선택된 하나 이상의 항암제를 추가로 함유할 수 있다. 그리고 상기 복어추출액은 복어를 개복하여 알 1kg을 취한후 물 3 liter를 넣고, 24시간 동안 약 100℃로 가열하면서 추출한 후 부유물을 제거하기 위해 통상의 방법으로 원심분리한 후 그 상청액을 취하여 제조된다.In order to achieve the above object, the present invention is a pharmaceutical composition for anticancer treatment containing a blowfish extract as an active ingredient and a pharmaceutically acceptable additive, the active ingredient is 5-fluorine known as an anticancer agent in addition to the blowfish extract It may further contain one or more anticancer agents selected from the group consisting of uracil, methotrexate, adriamycin, taxol. The puffer fish extract is prepared by opening the puffer fish, taking 1 kg of eggs, adding 3 liters of water, extracting while heating to about 100 ° C. for 24 hours, and then centrifuging in a conventional manner to remove suspended solids. .
이하, 첨부된 도면을 참조하여 본 발명의 바람직한 실시예를 자세히 설명하기로 한다.Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to the accompanying drawings.
도 1은 래트 1차 배양 정상 간 세포에 대한 복어 추출액의 세포분열 억제효과 실험결과 그래프이고, 도 2는 마우스 정상 비장 세포에 대한 복어 추출액의 세포분열 억제효과 실험결과 그래프이며, 도 3은 간 암세포에 대한 복어 추출액의 세포분열 억제효과 실험결과 그래프이다.1 is a graph showing the results of inhibition of cell division of blowfish extract on rat primary cultured normal liver cells, Figure 2 is a graph showing the results of cell division inhibition effect of pufferfish extract on mouse normal spleen cells, Figure 3 is a liver cancer cell Inhibitory effect of the blowfish extract on cell division.
본 발명은 복어 추출액을 활성 성분으로 함유하는 항암 치료용 약학 조성물에 관한 것이다. 이러한 본 발명의 복어 추출액은 복어를 물로 가열하면서 추출하여 얻으며, 이 복어 추출액 외에 환자의 복용상의 편의를 위하여 기타 약학적으로 허용되는 첨가제, 예를 들면 안정화제, 방향제, 교미제 등을 첨가할 수 있다.The present invention relates to a pharmaceutical composition for treating anticancer containing a puffer fish extract as an active ingredient. The puffer fish extract of the present invention is obtained by extracting the puffer fish while heating with water, and other pharmaceutically acceptable additives, such as stabilizers, fragrances, copulation agents, etc. can be added for the convenience of the patient in addition to the puffer fish extract. have.
또한, 본 발명의 항암치료용 약학 조성물은 항암제로 공지된 다른 활성성분을 추가로 함유하여 상승적 항암 효과를 가질 수 있다. 본 발명의 복어 추출액에 첨가될 수 있는 항암제의 종류에는 특별한 제한이 없으며, 구체적으로 5-플루오로우라실, 메토트렉세이트, 아드리아마이신, 탁솔 등을 들 수 있다.In addition, the anticancer pharmaceutical composition of the present invention may further contain a synergistic anticancer effect by further containing other active ingredients known as anticancer agents. The type of anticancer agent that can be added to the puffer fish extract of the present invention is not particularly limited, and specific examples thereof include 5-fluorouracil, methotrexate, adriamycin, and taxol.
본 발명의 복어 추출액이 항암제로 사용되기 위해서는 정상 세포에 대해서는 세포분열 억제 작용이 약하고, 암 세포에 대해서는 강력한 세포분열 억제 효과를 나타냄으로써 임상에서 사용될 수 있을 정도로 독성이 적어야 할 것이다. 따라서 본 발명의 복어 추출액의 정상 제포와 암 세포에 대한 세포분열 억제 효과를 각각 검색하기 위하여 래트의 정상 간세포와 마우스의 정상 비장 세포 및 간암 세포에 대한 세포 잔존율 시험(viability test)을 하기 실시예에 기재한 바와 같은 방법으로 행하였다.In order for the puffer fish extract of the present invention to be used as an anticancer agent, the cell division inhibitory effect on the normal cell is weak and the cytotoxic effect on the cancer cell should be low enough to be used in the clinic. Therefore, in order to detect the effect of inhibiting the division of the puffer fish extract of the present invention on the normal blastocyst and cancer cells, the cell viability test of the normal hepatocytes of the rat and the normal spleen cells and liver cancer cells of the mouse is performed in the following Examples It carried out by the method as described in the following.
실시예 1: 복어 추출액의 제조 Example 1 Preparation of Pufferfish Extract
복어를 개복하여 알 1kg을 취한 후 물 3 liter를 넣고 24시간 동안 약 100℃로 가열하면서 추출한다. 추출이 끝난 후 부유물을 제거하기 위해 통상의 방법으로 원심분리한 후 그 상청액을 취하여 본 발명의 복어 추출액을 제조하였다.Open the puffer fish, take 1kg of egg, add 3 liters of water, and extract it while heating to about 100 ℃ for 24 hours. After extraction, the blowfish extract of the present invention was prepared by centrifugation in a conventional manner to remove the suspended solids and taking the supernatant.
실시예 2-1: 래트 1차 배양 정상 간 세포에 대한 복어 추출액의 세포분열 억제 효과 실험 Example 2-1 Experiment of Inhibition of Cell Division of Puffer Fish Extract on Rat Primary Cultured Normal Liver Cells
래트의 1차 배양 정상 간 세포들을 포함하는 배지에 대해서 본 발명의 복어 추출액을 0, 30, 60, 120㎍/㎖ 농도로 각각 첨가하였을 때 얻어진 세포의 잔존율을 도 1에 도시하였다. 도 1을 참조하면, 횡축은 시간(hrs)을 나타내고 종축은 잔존율(% viability)을 나타내며, 그래프에서 "◆"는 복어 추출액을 농도 0으로 첨가한 경우의 세포 잔존율이고, "■"는 복어 추출액을 농도 30㎍/㎖으로 첨가한 경우의 세포 잔존율이고, "△"는 복어 추출액을 농도 60㎍/㎖로 첨가한 경우의 세포 잔존율이며, "×"는 복어 추출액을 농도 120㎍/㎖로 첨가한 경우의 세포 잔존율을 나타낸다.The residual ratio of the cells obtained when the puffer fish extract of the present invention was added at concentrations of 0, 30, 60, and 120 µg / ml, respectively, in a medium containing primary cultured normal liver cells of rats is shown in FIG. 1. Referring to FIG. 1, the axis of abscissas represents time (hrs) and the axis of ordinates represents% viability. In the graph, "◆" is the cell survival rate when puffer fish extract is added at concentration 0, and "■" is The cell residual ratio when the pufferfish extract was added at a concentration of 30 µg / ml, "△" is the cell residual ratio when the pufferfish extract was added at a concentration of 60 µg / ml, and "x" is 120 µg of the pufferfish extract. The cell residual ratio when added at / ml is shown.
실시예 2-2 :마우스 정상 비장 세포에 대한 복어 추출액의 세포분열 억제 효과 실험 Example 2-2: Experiment of Effects of Inhibiting Cell Division of Pufferfish Extract on Mouse Normal Spleen Cells
마우스 정상 비장 세포들의 배지에 대해서 본 발명의 복어 추출액을 0, 30, 60, 120㎍/㎖ 농도로 각각 첨가하였을 때 얻어진 세포의 잔존율을 도 2에 도시하였다. 도 2를 참조하면, 횡축은 시간(hrs)을 나타내고 종축은 잔존율(% viability)를 나타내며, 그래프에서 "◆"는 복어 추출액을 농도 0으로 첨가한 경우의 세포 잔존율이고, "■"는 복어 추출액을 농도 30㎍/㎖으로 첨가한 경우의 세포 잔존율이고, "△"는 복어 추출액을 농도 60㎍/㎖로 첨가한 경우의 세포 잔존율이며, "×"는 복어 추출액을 농도 120㎍/㎖로 첨가한 경우의 세포 잔존율을 나타낸다.The residual rate of the cells obtained when the puffer fish extract of the present invention was added at concentrations of 0, 30, 60, and 120 µg / ml, respectively, was shown in FIG. 2. Referring to FIG. 2, the horizontal axis represents time (hrs) and the vertical axis represents% viability. In the graph, "◆" represents cell survival rate when puffer fish extract is added at a concentration of 0, and "■" represents The cell residual ratio when the pufferfish extract was added at a concentration of 30 µg / ml, "△" is the cell residual ratio when the pufferfish extract was added at a concentration of 60 µg / ml, and "x" is 120 µg of the pufferfish extract. The cell residual ratio when added at / ml is shown.
실시예 3: 간 암세포에 대한 복어 추출액의 세포분열 억제 효과 실험 Example 3 Experiment of Cell Division Inhibition Effect of Puffer Fish Extract on Liver Cancer Cells
간 암세포들의 배지에 대해서 본 발명의 복어 추출액을 0, 30, 60, 120㎍/㎖ 농도로 각각 첨가하였을 때 얻어진 세포의 잔존율을 도 3에 도시하였다. 도 3을 참조하면, 횡축은 시간(hrs)을 나타내고 종축은 잔존율(% viability)을 나타내며, 그래프에서 "◆"는 복어 추출액을 농도 0으로 첨가한 경우의 세포 잔존율이고, "■"는 복어 추출액을 농도 30㎍/㎖으로 첨가한 경우의 세포 잔존율이고, "△"는 복어 추출액을 농도 60㎍/㎖로 첨가한 경우의 세포 잔존율이며, "×"는 복어 추출액을 농도 120㎍/㎖로 첨가한 경우의 세포 잔존율을 나타낸다.The residual rate of the cells obtained when the puffer fish extract of the present invention was added at concentrations of 0, 30, 60, and 120 µg / ml, respectively, was shown in FIG. 3. Referring to FIG. 3, the horizontal axis represents time (hrs) and the vertical axis represents% viability. In the graph, "◆" represents cell survival rate when puffer fish extract is added at a concentration of 0, and "■" represents The cell residual ratio when the pufferfish extract was added at a concentration of 30 µg / ml, "△" is the cell residual ratio when the pufferfish extract was added at a concentration of 60 µg / ml, and "x" is 120 µg of the pufferfish extract. The cell residual ratio when added at / ml is shown.
상기 정상 세포에 대한 실시예2-1, 실시예2-2과 암 세포에 대한 실시예3의세포 잔존율 시험 결과를 복어 추출액의 농도가 0㎍/㎖인 경우의 세포 잔존율을 100%로 하여 다른 농도에서의 세포 잔존율을 각각 계산한 값을 다음 표 1에 정리하였다.The cell residual ratio test results of Example 2-1, Example 2-2 and Example 3 of the normal cells were 100% of the cell residual ratio when the concentration of puffer fish extract was 0 µg / ml. The calculated values of the cell survival rates at different concentrations are summarized in Table 1 below.
상기 표 1에서 control을 100%로 볼 때 상대적인 값을 나타내고, 괄호안에는 원래의 값을 나타낸다. 그리고 0.4% tryphane blue로 cell viability test한 결과이고, hepG2는 MEM, hepatocyte는 williams'E CM, spleenocyte는 RPMI640으로 키운 것이다.Table 1 shows the relative values when the control is viewed as 100%, and the parentheses indicate the original values. Cell viability test results with 0.4% tryphane blue, hepG2 was raised to MEM, hepatocyte to williams'E CM, and spleenocyte to RPMI640.
상기 표 1의 결과로부터 본 발명의 복어 추출액은 정상 세포인 비장 세포에 대해서는 세포분열을 억제하는 효과가 적은 반면 간암세포에 대해서는 세포분열을 억제하는 효과가 크다는 것을 알 수 있다.From the results of Table 1, the puffer fish extract of the present invention has a small effect of inhibiting cell division for spleen cells, which are normal cells, but a large effect of inhibiting cell division for liver cancer cells.
또한, 정상 간 세포와 암 세포를 비교해보면, 고농도인 120㎍/㎖의 경우에는 모두 세포 분열이 억제되었으나 농도가 30 또는 60㎍/㎖인 경우에는 선택적으로 암 세포에 대해서 더욱 강력히 세포 분열을 억제하고 있어서 정확한 용량의 선택이 복어 추출액의 독성을 감소시키는 데 매우 중요다는 것을 알 수 있다.In addition, in comparison with normal liver cells and cancer cells, cell division was suppressed at high concentrations of 120 µg / ml, but more strongly at inhibiting cell division for cancer cells at concentrations of 30 or 60 µg / ml. It is understood that the correct dose selection is very important for reducing the toxicity of puffer fish extract.
이 실험 결과는 본 발명의 복어 추출액이 항암제로서 충분히 사용될 수 있을 정도로 독성은 적고, 암세포에 대한 선택적 세포분열 억제 효과는 탁월하다는 것을 보여준다.These experimental results show that the puffer fish extract of the present invention is low enough to be sufficiently used as an anticancer agent, and that the selective cell division inhibitory effect on cancer cells is excellent.
또한 본 발명의 복어 추출액을 하기 실시예4와 같이 암 환자들에게 투여하여 임상에서의 진통 효과 및 항암 효과를 관찰하였다.In addition, the puffer fish extract of the present invention was administered to cancer patients as in Example 4 to observe the analgesic and anticancer effects in the clinical.
실시예4: 말기 암 환자에 대한 임상 실험 Example 4 Clinical Trials in Terminal Cancer Patients
극심한 통증을 호소하는 유방암 환자 3명, 위암 환자 7명, 폐암 환자 2명, 간암 환자 3명, 난소암 환자 1명에게 통증을 호소할 때마다 그 통증의 정도에 따라서 본 발명의 복어 추출액 3 내지 60 ㎍ 정도의 분량을 물에 희석하여 음용시킨 결과 모든 환자에게서 탁월한 진통 효과를 얻을 수 있었다.Whenever pain is complained to 3 breast cancer patients, 7 stomach cancer patients, 2 lung cancer patients, 3 liver cancer patients and 1 ovarian cancer patient who complain of extreme pain, the puffer fish extract 3 to 3 according to the degree of pain As a result of diluting the amount of 60 μg in water and drinking it, excellent analgesic effect was obtained in all patients.
또한 위암 환자의 경우 음식물이 소화되는 정도가 현저히 개선되는 효과를 얻을 수 있었으며, 이는 복어 추출액의 항암효과로 인해 종양의 크기가 줄어든 데 기인한 것이다.In addition, gastric cancer patients were able to obtain a significant improvement in the degree of digestion of food, which is due to the reduction in tumor size due to the anticancer effect of puffer fish extract.
이상 살펴본 바와 같이, 본 발명의 복어 추출액은 암 환자에게 투여시 항암 효과를 얻을 수 있고 암 환자의 통증을 제어하는 효과도 얻을 수 있는 것이어서 통증을 호소하는 암 환자에게 투여시 항암 치료 효과는 물론이고, 진통 효과까지도 함께 얻어지는 장점을 가진 것이다.As described above, the puffer fish extract of the present invention can obtain an anticancer effect when administered to a cancer patient and can also control the pain of the cancer patient, as well as the anticancer treatment effect when administered to a cancer patient complaining of pain. It also has the advantage that even analgesic effect is obtained.
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
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| KR20040000037A (en) * | 2002-06-19 | 2004-01-03 | (주)케이씨티메디컬쎈터 | Composition for anticancer |
| KR100495173B1 (en) * | 2001-10-23 | 2005-06-13 | 윤황병 | Method for manufacturing of health food being use of nonpoisonous river puffer |
| KR100537437B1 (en) * | 2002-09-17 | 2005-12-21 | 김익수 | Anticancer drug composition containing swellfish extract |
| WO2006004377A1 (en) * | 2004-07-06 | 2006-01-12 | Pni Inc. | A polypeptide extraxt derived from swellfish and compositions for the prevention or treatment of cancer containing the extract |
| KR100603942B1 (en) * | 2004-05-10 | 2006-07-25 | 주식회사 푸드사이언스 | A seasoning composition for a cabbage kimch and a cabbage kimch prepared using the same |
| WO2007110221A1 (en) * | 2006-03-27 | 2007-10-04 | Wex Pharmaceuticals Inc. | Use of sodium channel blockers for the treatment of neuropathic pain developing as a consequence of chemotherapy |
| KR20200084704A (en) * | 2019-01-03 | 2020-07-13 | 대한바이오팜 주식회사 | Anti-Metastasis Composition comprising Pufferfish Extract |
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| JPH03153627A (en) * | 1989-11-11 | 1991-07-01 | ▲ゆ▼ 耀庭 | Medicament containing swellfish poison as pharmaceutically effective component, its preparation and extraction of said swellfish poison |
| EP1002535A1 (en) * | 1998-10-28 | 2000-05-24 | Hrissanthi Ikonomidou | New use of glutamate antagonists for the treatment of cancer |
| KR20020007710A (en) * | 2000-07-18 | 2002-01-29 | 김동춘 | Method for extracing tetrodotoxin |
| KR101145225B1 (en) * | 2009-12-02 | 2012-05-24 | 주식회사 아키폴리코퍼레이션 | A connector frame structure for exterior panel |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100495173B1 (en) * | 2001-10-23 | 2005-06-13 | 윤황병 | Method for manufacturing of health food being use of nonpoisonous river puffer |
| KR20040000037A (en) * | 2002-06-19 | 2004-01-03 | (주)케이씨티메디컬쎈터 | Composition for anticancer |
| KR100537437B1 (en) * | 2002-09-17 | 2005-12-21 | 김익수 | Anticancer drug composition containing swellfish extract |
| KR100603942B1 (en) * | 2004-05-10 | 2006-07-25 | 주식회사 푸드사이언스 | A seasoning composition for a cabbage kimch and a cabbage kimch prepared using the same |
| WO2006004377A1 (en) * | 2004-07-06 | 2006-01-12 | Pni Inc. | A polypeptide extraxt derived from swellfish and compositions for the prevention or treatment of cancer containing the extract |
| WO2007110221A1 (en) * | 2006-03-27 | 2007-10-04 | Wex Pharmaceuticals Inc. | Use of sodium channel blockers for the treatment of neuropathic pain developing as a consequence of chemotherapy |
| EP2394646A1 (en) * | 2006-03-27 | 2011-12-14 | Wex Medical Limited | Use of sodium channel blockers for the treatment of neuropathic pain developing as a consequence of chemotherapy |
| US9018222B2 (en) | 2006-03-27 | 2015-04-28 | Wex Medical Limited | Use of sodium channel blockers for the treatment of neuropathic pain developing as a consequence of chemotherapy |
| US10149852B2 (en) | 2006-03-27 | 2018-12-11 | Wex Pharmaceuticals Inc. | Use of sodium channel blockers for the treatment of neuropathic pain developing as a consequence of chemotherapy |
| US10624896B2 (en) | 2006-03-27 | 2020-04-21 | Wex Medical Limited | Use of sodium channel blockers for the treatment of neuropathic pain developing as a consequence of chemotherapy |
| US11419873B2 (en) | 2006-03-27 | 2022-08-23 | Wex Medical Limited | Use of sodium channel blockers for the treatment of neuropathic pain developing as a consequence of chemotherapy |
| KR20200084704A (en) * | 2019-01-03 | 2020-07-13 | 대한바이오팜 주식회사 | Anti-Metastasis Composition comprising Pufferfish Extract |
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