KR970702728A - Cancer Treatment and Metastasis Prevention - Google Patents

Cancer Treatment and Metastasis Prevention

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KR970702728A
KR970702728A KR1019960706101A KR19960706101A KR970702728A KR 970702728 A KR970702728 A KR 970702728A KR 1019960706101 A KR1019960706101 A KR 1019960706101A KR 19960706101 A KR19960706101 A KR 19960706101A KR 970702728 A KR970702728 A KR 970702728A
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hyaluronic acid
cancer
drug
daltons
molecular weight
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KR1019960706101A
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Korean (ko)
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윌리엄 제이 커래톨로
힐라 엘 프레드만
리차드 더블유 코르스메이어
모트 스티븐 알 르
루돌프 에드가 포크
사무엘 시몬 에스큘라이
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스피겔 알렌 제이
화이자 인코포레이티드
사무엘 시몬 에스큐라이
노르팔마코 인코포레이티드
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Publication of KR970702728A publication Critical patent/KR970702728A/en

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Abstract

본 발명은 출원인은 사람에서 암 특히 악성 종양 예로써 유방에서의 종양을 치료하는 신규한 방법을 제공하는데; 이 방법은 1) 암을 치료하는데 적합한 항-암제의 효과적인 비-독성 약량(예로서, 1 내지 2mg노반트론(tm)(Mitoxantrone) 또는 다른 화학요법제(인터페론 또는 NSAID)와 멸균수에 분자량이 750,000 달톤 이하(예로서 150,000-225,000달톤)을 가지는 제약학적 수용 가능한 염 적절하게는 히알루노네이트 나트륨(예로써 10-20mg 히알루노네이트나트륨) 효과량으로 구성된 제약학적 조성물의 비-독성 약량을 종양내로 직접 주입하고(종양의 크기는 종양내로 직접 주입될 수 있는 약량을 한정한다); 2) 복합된 제약학적 조성물의 약량을 적절하게는 전신에(적절하게는 정맥내로) 투여하고 이때 조성물의 구성은 ⅰ) 히알루론산형의 효과량(분자량이 750,000달톤(예로서 150,000-225,000달톤) 이하의 분자량을 가지는 히아루론산과 제약학적 수용 가능한 염)예로써 약 100-200mg 또는 그 이상(독성이 부족하고 히알루론산의 약량이 약 200mg/70kg 사람을 초과하는 경우에 함께 투여되는 임의 약물 (예로써 NSAID)의 부작용을 감소시키기 위해) ⅱ) 약물 : 이때 약물은 a) 비-스테로이드성 항염중제(NSAID) 약 30mg 내지 100mg(예로써 케토라락의 트로메타민염(상표 Toradol로 시판된)과 디클로페낙 또는 디클로페낙나트륨(예로써 상표 Voltarol)에서 선택되고, b) (1)에서 상술한 화학 요법제(항-암제 또는 암치료에 적합한 약물)과 이의 복합물의 효과적인 비독성 약물, 그리고 선택적으로 ⅲ)항-산화제 예로써 비타민 C(25mg 비타민C)로 구성된다.The present invention provides a novel method for treating cancer in humans, particularly malignant tumors such as breast in the breast; This method provides for the use of 1) an effective non-toxic dose of an anti-cancer agent suitable for treating cancer (eg, 1-2 mg novantron (tm) or other chemotherapeutic agent (interferon or NSAID) and molecular weight in sterile water. Pharmaceutically acceptable salts having 750,000 Daltons or less (e.g. 150,000-225,000 Daltons) Tumors are non-toxic doses of pharmaceutical compositions suitably composed of an effective amount of sodium hyaluronate (e.g. 10-20 mg sodium hyaluronate). Injected directly into the tumor (the size of the tumor defines the amount of the drug that can be injected directly into the tumor); and 2) the dosage of the combined pharmaceutical composition is suitably administered systemically (appropriately intravenously) and the composition of the composition Iii) effective amounts of hyaluronic acid type (hyaluronic acid and a pharmaceutically acceptable salt with a molecular weight of 750,000 Daltons (eg 150,000-225,000 Daltons)), e.g. about 100-200 mg or more ( To reduce the side effects of any drug (eg NSAID) administered together when the toxicity is low and the dose of hyaluronic acid exceeds about 200 mg / 70 kg human) ii) Drug: wherein the drug is a) non-steroidal anti-inflammatory About 30 mg to 100 mg (NSAID) (e.g., tromethamine salt from Ketorak (tradename Toradol) and diclofenac or diclofenac sodium (for example trademark Voltarol)), and b) the chemistry described in (1). It consists of an effective nontoxic drug of therapy (an anti-cancer drug or drug suitable for cancer treatment) and a combination thereof, and optionally iii) vitamin C (25 mg vitamin C) as an anti-oxidant.

Description

암치료와 전이예방(Cancer Treatment and Metastasis Prevention)Cancer Treatment and Metastasis Prevention

본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음Since this is an open matter, no full text was included.

Claims (19)

사람에서 전이의 예방/감소를 위해 사람에 암치료하는 방법에 있어서, 이 방법은 1) 제약학적 조성물의 비-독성 효과량을 종양에 직접 주사하는데 이때 조성물은 멸균수에 750,000 달콘 이하의 평균 분자량을 가지는 히알루론산 그리고/또는 제약학적 수용 가능한 염으로 구성된 집단에서 선택된 히알루론산형의 효과약량과 암을 치료하기에 적합한 항-암제 그리고/또는 약물의 비독성 효과량으로 구성되고, 그리고 2) 제약학적 조성물의 비-독성 효과량을 전신으로 투여하는데, 이때 조성물은 히알루론산과 이의 제약학적 수용 가능한 염 ⅰ)적절하게는 평균 분자량이 750,000 단톤 이하인 분자량을 가지는 히알루노네이트나트륨에서 선택된 히알루논산 효과량 ⅱ) a) 비-스테로이드성 항-염증제(NSAIDs) b) 화학요법제와 이의 복합제 그리고 ⅲ) 선택적으로 항-산화제로 구성된 약물에서 선택된 약물로 구성되는 것을 특징으로 하는 방법.In the treatment of cancer in humans for the prevention / reduction of metastasis in humans, the method comprises the following steps: 1) direct injection of a non-toxic effective amount of a pharmaceutical composition into a tumor, wherein the composition is in sterile water with an average molecular weight of 750,000 Dalcon or less An effective dose of the hyaluronic acid type selected from the group consisting of hyaluronic acid and / or a pharmaceutically acceptable salt having a non-toxic effective amount of an anti-cancer agent and / or drug suitable for treating cancer, and 2) pharmaceutical The systemically administers a non-toxic effective amount of the pharmaceutical composition, wherein the composition is hyaluronic acid and its pharmaceutically acceptable salt iii) an effective amount of hyaluronic acid selected from sodium hyaluronate having an average molecular weight of 750,000 Daltons or less. Ii) a) non-steroidal anti-inflammatory agents (NSAIDs) b) chemotherapeutic agents and combinations thereof and iii) optionally anti- Characterized in that the configuration at the drugs consisting of agents to the selected drug. 제1항에 있어서, 치료 빈도는 한달에 1-4회 또는 그 이상이 되는 것을 특징으로 하는 방법.The method of claim 1, wherein the treatment frequency is 1-4 times or more per month. 제1항에 있어서, 암은 유방암이고, 유방에 있는 악성 종양에 직접 주사와 전신투여의 빈도는 1-3회(한달) 또는 그 이상이 되는 것을 특징으로 하는 방법.The method of claim 1, wherein the cancer is breast cancer and the frequency of direct injection and systemic administration to the malignant tumor in the breast is 1-3 times (monthly) or more. 제1,2 또는 3항에 있어서, 전신투여는 정맥투여인 것을 특징으로 하는 방법.4. The method of claim 1, 2 or 3, wherein the systemic administration is intravenous administration. 제1,2 또느 3항에 있어서, 과온증이 있는 신체를 치료하는 것으로 구성된 것을 특징으로 하는 방법.4. A method according to claim 1, 2 or 3 which consists in treating the body with hyperthermia. 사람에게 전이의 감소를 위해 사람에 암치료하는 방법에 있어서, 이 방법은 1) 암으로 고통받는 환자에게 암을 치료하는 약의 효과량 단독 또는 750,000 달톤 이하의 평균 분자량을 가지는 히알루론산 그리고/또는 제약학적 수용 가능한 염으로 구성된 집단에서 선택된 히알루론산형의 효과약량과 같이 전신 투여하고; 그리고 2) 제약학적 조성물의 비-독성 효과량을 전신으로 투여하는데, 이때 조성물은 히알루론산과 이의 제약학적 수용 가능한 염 ⅰ) 적절하게는 평균 분자량이 750,000 달톤 이하인 분자량을 가지는 히알루노네이트 나트륨에서 선택된 히알루논산 효과량 ⅱ) a) 비-스테로이드성 항-염증제(NSAIDs) b) 화학요법제와 이의 복합제 그리고 ⅲ) 선택적으로 항-산화제로 구성된 약물에서 선택된 약물로 구성되는 것을 특징으로 하는 방법.A method of treating cancer in humans for reducing metastasis to humans, the method comprising: 1) hyaluronic acid and / or having an effective amount of a drug for treating cancer alone or an average molecular weight of 750,000 Daltons or less in a patient suffering from cancer Systemic administration of an effective dose of a hyaluronic acid type selected from the group consisting of pharmaceutically acceptable salts; And 2) systemically administering a non-toxic effective amount of the pharmaceutical composition, wherein the composition is selected from hyaluronic acid and its pharmaceutically acceptable salt iii) suitably selected from sodium hyaluronate having an average molecular weight of 750,000 Daltons or less. Hyaluronic acid effective amount ii) a) non-steroidal anti-inflammatory agents (NSAIDs) b) a chemotherapeutic agent and a combination thereof and iii) a drug selected from drugs consisting of an anti-oxidant. 제6항에 있어서, (1)와 (2)단계를 필요한 만큼 반복하는 것을 특징으로 하는 방법.7. The method of claim 6, wherein steps (1) and (2) are repeated as necessary. 암전이(전이 또는 전이효과로 인해 고통을 받는)를 가지는 암환자에게 이와 같은 감소를 위한 방법에 있어서, 이 방법은 1) 암으로 고통받는 환자에게 암을 치료하는 약의 효과량 단독 또는 750,000 달톤 이하의 평균 분자량을 가지는 히알루론산 그리고/또는 제약학적 수용 가능한 염으로 구성된 집단에서 선택된 히알루론산형의 효과약량과 같이 전신 투여하고; 그리고 2) 제약학적 조성물의 비-독성 효과량을 전신으로 투여하는데, 이때 조성물은 히알루론산과 이의 제약학적 수용 가능한 염 ⅰ) 적절하게는 평균 분자량이 750,000 달톤 이하인 부자량을 가지는 히알루노네이트 나트륨에서 선택된 히알루논산 효과량 ⅱ) a) 비-스테로이드성 항-염증제(NSAIDs) b) 화학요법제와 이의 복합제 그리고 ⅲ) 선택적으로 항-산화제로 구성된 약물에서 선택된 약물로 구성되는 이때 투약은 암치료기간 동안에 정규적 간격으로 반복되는 것을 특징으로 하는 방법.A method for such a reduction in cancer patients with cancer metastasis (which suffers from a metastasis or metastasis effect), the method comprising: 1) an effective amount of a drug to treat cancer alone or 750,000 daltons in a patient suffering from cancer Systemic administration with an effective dose of a hyaluronic acid type selected from the group consisting of hyaluronic acid and / or a pharmaceutically acceptable salt having an average molecular weight of: And 2) systemically administering a non-toxic effective amount of the pharmaceutical composition, wherein the composition is selected from hyaluronic acid and its pharmaceutically acceptable salt iii) suitably selected from sodium hyaluronate having a molecular weight below 750,000 daltons of average molecular weight. Hyaluronic acid effective amount ii) a) non-steroidal anti-inflammatory agents (NSAIDs) b) chemotherapeutic agents and combinations thereof and iii) drugs selected from drugs consisting of anti-oxidants, wherein the dosing is carried out during cancer treatment. Characterized in that repeated at regular intervals. 제8항에 있어서, 치료 방법은 1달에 1-4회 투여되는 것을 특징으로 하는 방법.The method of claim 8, wherein the method of treatment is administered 1-4 times per month. 1)전신투여용으로 비독성 약량은 ⅰ) 750,000 달톤 이하의 평균 분자량을 가지는 히알루론산 그리고/또는 제약학적 수용 가능한 염으로 구성된 집단에서 선택된 히알루론산형의 효과약량과; 그리고 ⅱ) a) 비-스테로이드성 항-염증제(NSAIDs) b) 화학요법제와 이의 복합제 그리고 ⅲ) 선택적으로 항-산화제로 구성된 약물에서 선택되고 2) 주사에 적합한 제약학적 조성물의 비-독성 효과량, 이때 약량은 주사 가능한 형이고 암을 치료하기에 적합한 항-암제 또는 약물의 효과량과 멸균수에 750,000 달톤 이하의 평균 분자량을 가지는 히알루론산 그리고/또는 제약학적 수용 가능한 염으로 구성된 집단에서 선택된 히알루론산형의 효과약량으로 구성된 것을 특징으로 하는 제약학적 조성물.1) the non-toxic dose for systemic administration is i) an effective dose of a hyaluronic acid type selected from the group consisting of hyaluronic acid and / or a pharmaceutically acceptable salt having an average molecular weight of 750,000 Daltons or less; And ii) a) non-steroidal anti-inflammatory agents (NSAIDs) b) a chemotherapeutic agent and a combination thereof and iii) a drug optionally consisting of an anti-oxidant and 2) a non-toxic effect of a pharmaceutical composition suitable for injection Amount, wherein the dosage is injectable and is selected from the group consisting of an effective amount of an anti-cancer agent or drug suitable for treating cancer and hyaluronic acid and / or a pharmaceutically acceptable salt having an average molecular weight of 750,000 Daltons or less in sterile water A pharmaceutical composition comprising an effective dose of hyaluronic acid type. 제10항에 있어서, (1) 약물은 NSAID인 것을 특징으로 하는 조성물.The composition of claim 10, wherein (1) the drug is an NSAID. 제10 또는 11항에 있어서, 히알루론산은 히알로노네이트 나트륨인 것을 특징으로 하는 조성물.12. The composition of claim 10 or 11, wherein the hyaluronic acid is sodium hyaluronate. 제약학적 조성물의 효과적인 비-독성 약량의 용도에 있어서, 약량은 암을 치료하는데 사용하기에 적합한 항-암제 그리고/또는 약물과 750,000 달톤 이하의 평균 분자량을 가지는 히알루론산 그리고/또는 제약학적 수용 가능한 염으로 구성된 집단에서 선택된 히알루론산혀으이 효과약량과 히알루론산과 이의 제약학적 수용 가능한 염 ⅰ) 적절하게는 평균 분자량이 750,000 달톤이하인 분자량을 가지는 히알루노네이트 나트륨에서 선택된 히알루논산 효과량 ⅱ) a) 비-스테로이드성 항-염증제(NSAIDs) b) 화학요법제와 이의 복합제 그리고 ⅲ) 선택적으로 항-산화제로 구성된 약물에서 선택된 약물로 구성되고 a) 환자에서 암을 치료하고 b) 암으로 고생하는 환자에 전이를 막고, 그리고 c) 임파계 또는 간으로 약물을 수송하기 위한 것을 특징으로 하는 용도.In the use of an effective non-toxic dosage of a pharmaceutical composition, the dosage is an anti-cancer agent and / or drug suitable for use in treating cancer with hyaluronic acid and / or a pharmaceutically acceptable salt having an average molecular weight of 750,000 Daltons or less. Hyaluronic acid selected from the group consisting of hyaluronic acid and hyaluronic acid and its pharmaceutically acceptable salts i) hyaluronic acid effective amount selected from sodium hyaluronate, suitably with an average molecular weight of 750,000 Daltons or less ii) a) -Steroidal anti-inflammatory drugs (NSAIDs) b) consisting of a drug selected from a chemotherapeutic agent and a combination thereof, and iii) a drug optionally consisting of an anti-oxidant, a) treating cancer in a patient and b) treating a patient suffering from cancer. Preventing metastasis, and c) transporting the drug to the lymphatic system or liver. 약량은 암을 치료하는데 사용하기에 적합한 항-암제 그리고/또는 약물 단독 또는 (Ⅰ) 750,000 달톤 이하의 평균 분자량을 가지는 히알루론산 그리고/또는 제약학적 수용 가능한 염으로 구성된 집단에서 선택된 히알루론산형의 효과약량과 복합하여 구성된 제약학적 조성물의 효과량과 (Ⅱ) 효과적인 약량은 히알루론산과 이의 제약학적 수용 가능한 염 ⅰ) 적절하게는 평균 분자량이 750,000 달톤 이하인 분자량을 가지는 히알루노네이트 나트륨에서 선택된 히알루논산 효과량 그리고 ⅱ) a) 비-스테로이드성 항-염증제(NSAIDs) b) 화학요법제와 이의 복합제 그리고 선택적으로 ⅲ) 항-산화제로 구성된 것에서 선택된 약물로써 a) 환자에게 암을 치료하고 b) 암으로 고생하는 환자에 전이를 막고, 그리고 c) 임파계 또는 간으로 약물을 수송하기 위한 것을 특징으로 하는 용도.The dosage is the effect of a hyaluronic acid type selected from the group consisting of anti-cancer agents and / or drugs alone or (I) hyaluronic acid having an average molecular weight of 750,000 Daltons or less and / or pharmaceutically acceptable salts suitable for use in treating cancer. The effective amount of the pharmaceutical composition composed in combination with the dosage and (II) the effective dosage are hyaluronic acid and its pharmaceutically acceptable salt iii) hyaluronic acid effect selected from sodium hyaluronate, suitably with an average molecular weight of 750,000 Daltons or less And ii) a) non-steroidal anti-inflammatory agents (NSAIDs) b) a drug selected from a combination of chemotherapeutic agents and combinations thereof and optionally iii) anti-oxidants, a) treating the patient with cancer and b) Prevent metastasis to the suffering patient, and c) transport the drug to the lymphatic system or liver. Use. 암치료에 적합한 항-암제 효과적인 비-독성 약량과 멸균수에 750,000 달톤 이하의 분자량을 가지는 히알루론산 그리고/또는 제약학적 수용 가능한 염과 이의 복합물에서 선택된 히알루론산의 효과량이 암으로 고통받는 환자에서 전이를 예방하기 위한 제약학적 조성물의 제조시에 사용되는 것을 특징으로 하는 용도.Anti-cancer agents suitable for cancer treatment Effective amounts of hyaluronic acid and / or pharmaceutically acceptable salts and combinations thereof with hyaluronic acid having a molecular weight of 750,000 Daltons or less in sterile water and effective amounts of hyaluronic acid selected from the combinations in patients suffering from cancer Use in the manufacture of a pharmaceutical composition for preventing the use. 제16항에 있어서, 주사형인 것을 특징으로 하는 용도.Use according to claim 16, characterized in that it is injectable. 히알루론산과 이의 제약학적 수용 가능한 염 ⅰ) 적절하게는 평균 분자량이 750,000 달톤 이하인 분자량을 가지는 히알루노네이트나트륨에서 선택된 히알루논산 효과량 ⅱ) a) 비-스테로이드성 항-염증제(NSAIDs) b) 화학요법제와 이의 복합제 그리고 ⅲ) 선택적으로 항-산화제로 구성된 약물에서 선택된 약물로 구성되는 것을 특징으로 하는 용도.Hyaluronic acid and its pharmaceutically acceptable salts i) hyaluronic acid effective amount selected from sodium hyaluronate, suitably with an average molecular weight of 750,000 Daltons or less ii) a) non-steroidal anti-inflammatory agents (NSAIDs) b) chemical And a drug selected from therapies, combinations thereof, and optionally drugs consisting of anti-oxidants. 제18항에 있어서, 정맥내 투여 간으한 형인 것을 특징으로 하는 용도.,Use according to claim 18, characterized in that the intravenous administration is simple. (Ⅰ)암치료에 적합항 항-암제의 효과적인 비-독성약량과 멸균수에 750,000 달톤 이하의 분자량을 가지는 히알루론산 그리고/또는 제약학적 수용 가능한 염과 이의 복합물에서 선택된 히알루론산의 효과량과 히알루론산과 이의 제약학적 수용 가능한 염, (Ⅱ) (ⅰ) 적절하게는 평균 분자량의 750,000 달톤 이하인 분자량을 가지는 히알루노네이트 나트륨에서 선택된 히알루논산 효과량 ⅱ) a) 비-스테로이드성 항-염증제(NSAIDs) b) 화학요법제와 이의 복합제 그리고 ⅲ) 성분(Ⅰ)로 구성된 조성물(1)와 성분(Ⅱ)로 구성된 조성물(2)의 2개 조성물의 제조시에 항-산화제로 구성된 약물에서 선택된 약물로 구성되는 제약학적 조성물은 a) 환자에서 암의 치료, b) 암으로 고통받는 환자에서 전이방지 그리고 c) 임파계와 간으로 약물 수송을 위한 것을 특징으로 하는 용도.(I) Effective amounts of hyaluronic acid and / or hyaluronic acid selected from a combination of hyaluronic acid and / or pharmaceutically acceptable salts having a molecular weight of 750,000 Daltons or less in sterile water and an effective non-toxic dose of anti-cancer agent suitable for cancer treatment Hyaluronic acid effective amount selected from lonic acid and its pharmaceutically acceptable salts, (II) (iii) sodium hyaluronate, suitably with a molecular weight of 750,000 daltons of average molecular weight or less, ii) a) non-steroidal anti-inflammatory agents (NSAIDs) b) a drug selected from a drug consisting of an anti-oxidant in the manufacture of two compositions, a chemotherapeutic agent and a combination thereof and a composition (1) consisting of component (I) and composition (2) consisting of component (II). A pharmaceutical composition consisting of a) for the treatment of cancer in a patient, b) for preventing metastasis in a patient suffering from cancer and c) for drug transport to the lymphatic system and liver. ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.※ Note: The disclosure is based on the initial application.
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CN1151118A (en) 1997-06-04
RU2162327C2 (en) 2001-01-27
AU696373B2 (en) 1998-09-10
WO1995030423A3 (en) 1995-12-21
JPH09512797A (en) 1997-12-22
CZ308996A3 (en) 1998-01-14
WO1995030423A2 (en) 1995-11-16
SK137996A3 (en) 1998-08-05
CA2122519A1 (en) 1995-10-30

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