JPH0149129B2 - - Google Patents
Info
- Publication number
- JPH0149129B2 JPH0149129B2 JP56204135A JP20413581A JPH0149129B2 JP H0149129 B2 JPH0149129 B2 JP H0149129B2 JP 56204135 A JP56204135 A JP 56204135A JP 20413581 A JP20413581 A JP 20413581A JP H0149129 B2 JPH0149129 B2 JP H0149129B2
- Authority
- JP
- Japan
- Prior art keywords
- leukemia
- blood
- pantethine
- lysolecithin
- cells
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 208000032839 leukemia Diseases 0.000 claims description 30
- DJWYOLJPSHDSAL-UHFFFAOYSA-N Pantethine Natural products OCC(C)(C)C(O)C(=O)NCCC(=O)NCCSSCCNC(=O)CCNC(=O)C(O)C(C)(C)CO DJWYOLJPSHDSAL-UHFFFAOYSA-N 0.000 claims description 16
- DJWYOLJPSHDSAL-ROUUACIJSA-N pantethine Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSSCCNC(=O)CCNC(=O)[C@H](O)C(C)(C)CO DJWYOLJPSHDSAL-ROUUACIJSA-N 0.000 claims description 16
- 229960000903 pantethine Drugs 0.000 claims description 16
- 235000008975 pantethine Nutrition 0.000 claims description 16
- 239000011581 pantethine Substances 0.000 claims description 16
- ASWBNKHCZGQVJV-UHFFFAOYSA-N (3-hexadecanoyloxy-2-hydroxypropyl) 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(O)COP([O-])(=O)OCC[N+](C)(C)C ASWBNKHCZGQVJV-UHFFFAOYSA-N 0.000 claims description 12
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 9
- 239000000787 lecithin Substances 0.000 claims description 9
- 229940067606 lecithin Drugs 0.000 claims description 9
- 235000010445 lecithin Nutrition 0.000 claims description 9
- 210000004698 lymphocyte Anatomy 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 5
- 229940124597 therapeutic agent Drugs 0.000 claims description 5
- 239000010836 blood and blood product Substances 0.000 claims description 4
- 229940125691 blood product Drugs 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims 1
- 210000004369 blood Anatomy 0.000 description 22
- 239000008280 blood Substances 0.000 description 22
- 210000004027 cell Anatomy 0.000 description 16
- 230000000694 effects Effects 0.000 description 9
- 238000011282 treatment Methods 0.000 description 8
- 241000282414 Homo sapiens Species 0.000 description 4
- 230000007910 cell fusion Effects 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 102000014190 Phosphatidylcholine-sterol O-acyltransferase Human genes 0.000 description 2
- 108010011964 Phosphatidylcholine-sterol O-acyltransferase Proteins 0.000 description 2
- 238000004820 blood count Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- DEXFNLNNUZKHNO-UHFFFAOYSA-N 6-[3-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-3-oxopropyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)C(CCC1=CC2=C(NC(O2)=O)C=C1)=O DEXFNLNNUZKHNO-UHFFFAOYSA-N 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 238000011254 conventional chemotherapy Methods 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Description
【発明の詳細な説明】
本発明は白血病治療剤に関するものであり、更
に詳細には、生体由来のリンパ球及びリゾレシチ
ンを含有する健常人血液製剤よりなる白血病治療
剤に関するものである。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a therapeutic agent for leukemia, and more particularly, to a therapeutic agent for leukemia comprising a healthy human blood product containing lymphocytes of biological origin and lysolecithin.
白血病の医学的治療法として、従来化学療法剤
あるいはステロイドホルモンが使用されている
が、いずれも強い副作用のため長期投与が不可能
の場合があり、効果不足あるいは副作用のため不
幸な転帰を招く場合が少くない。本発明によるパ
ンテチンおよびレシチンはいずれも副作用がきわ
めてわずかであり、白血病に対して有効な治療法
(剤)を提供し得るものである。 Conventional chemotherapy drugs or steroid hormones have been used as medical treatments for leukemia, but they have strong side effects that sometimes make long-term administration impossible, and sometimes lead to unfortunate outcomes due to lack of efficacy or side effects. There are quite a few. Both pantethine and lecithin according to the present invention have very few side effects and can provide an effective treatment method (agent) for leukemia.
即ち、本発明は生体が腫瘍細胞を排除するに当
つては細胞依存性免疫能が関与していること、白
血病患者ではこの免疫能が低下していること及び
細胞依存性免疫に於ては免疫能の主役であるリン
パ球が白血病細胞と細胞融合することによつて作
用を発現すること等の事実に鑑み、本発明者は健
常人血液のリンパ球の細胞融合性を高めこの血液
を用いての白血病の治療に着目し完成するに至つ
たものである。すなわち本発明者は、細胞融合を
促進する生体の物質であるリゾレシチンの存在下
では健康人血液が白血球細胞を強力に変形破壊す
ることを見出し、この作用を白血病の治療に応用
して本発明を完成したものである。 That is, the present invention shows that cell-dependent immune capacity is involved in the elimination of tumor cells by the living body, that this immune capacity is reduced in leukemia patients, and that cell-dependent immunity In view of the fact that lymphocytes, which play a major role in this function, express their effects through cell fusion with leukemia cells, the present inventor has developed a method to increase the cell fusion property of lymphocytes in healthy human blood and use this blood to This work was completed by focusing on the treatment of leukemia. That is, the present inventors have discovered that healthy human blood strongly deforms and destroys white blood cells in the presence of lysolecithin, a biological substance that promotes cell fusion, and has developed the present invention by applying this effect to the treatment of leukemia. It is completed.
すなわち、本発明は、パンテチン又はパンテチ
ンとレシチン投与1〜4時間後に採取した健常人
血液製剤からなる白血病治療剤を提供するもので
ある。 That is, the present invention provides a therapeutic agent for leukemia comprising pantethine or a blood product from a healthy individual collected 1 to 4 hours after administration of pantethine and lecithin.
以下実験例に則して更に詳しく説明する。 A more detailed explanation will be given below based on experimental examples.
実験に用いた健常人(52才男性)の血液は、血
液型B型で白血球数は8300、このうちリンパ球を
30%含むものであり、一方、慢性骨髄性白血病患
者(79才女性)の血液は、血液型B型で、白血球
数は25700、このうち白血病細胞が91%を占め、
リンパ球は4%のものである。これ等を用いて次
の実験を行つた。 The blood of a healthy person (a 52-year-old man) used in the experiment had blood type B and a white blood cell count of 8300, of which lymphocytes were
On the other hand, the blood of a chronic myeloid leukemia patient (a 79-year-old woman) has blood type B and a white blood cell count of 25,700, of which leukemia cells account for 91%.
Lymphocytes account for 4%. The following experiment was conducted using these.
実験1 白血病患者の血液のみを37℃にて2時間
保温した後に染色し、白血病細胞のうちで変形
破壊された細胞を顕微鏡下で検索したが全く見
出されなかつた。Experiment 1 Only the blood of a leukemia patient was incubated at 37°C for 2 hours and then stained. Among the leukemia cells, deformed and destroyed cells were searched under a microscope, but no cells were found.
実験2 白血病患者の血液にリゾレシチンを25μ
g/mlの割合で添加し、37℃にて2時間保温し
実験1.と同様に観測すると白血病細胞のうちで
5%が変形破壊されることが確認された。Experiment 2: Add 25μ of lysolecithin to the blood of leukemia patients.
It was confirmed that 5% of the leukemia cells were deformed and destroyed when it was added at a rate of 1.3 g/ml, kept at 37° C. for 2 hours, and observed in the same manner as in Experiment 1.
実験3 健常人血液と白血病患者の血液を1:1
の割合で混合し37℃にて2時間保温したのち実
験1.と同様に観測し白血病細胞の29%が破壊さ
れていることが確認された。Experiment 3 Blood from healthy people and blood from leukemia patients 1:1
The mixture was mixed at a ratio of 100% and kept at 37°C for 2 hours, and then observed in the same manner as in Experiment 1. It was confirmed that 29% of the leukemia cells had been destroyed.
実験4 健常人血液と白血病患者の血液を1:1
の割合で混じたものにリゾレシチン25μg/ml
を添加すると同様な観測の結果、白血病細胞の
79%が変形破壊されることが確認された。Experiment 4 Blood from healthy people and blood from leukemia patients 1:1
Lysolecithin 25μg/ml mixed with
As a result of similar observation, the addition of
It was confirmed that 79% were deformed and destroyed.
すなわち、実験4.の成績は、健康人のリンパ球
がリゾレシチンの存在下では白血病細胞と効果的
に細胞融合し、白血病細胞を強力に変形破壊し、
腫瘍細胞を排除することを示すものである。しか
し、リゾレシチンには強い溶血作用があるため、
そのままでは人に投与することができない。そこ
で本発明者は、別途に健常人に対するパンテチン
あるいはパンテチンとレシチンの併用投与で生体
自らが生体の許容範囲内でリゾレシチンを増やす
ことに注目し、この作用を白血病の治療に応用し
て成功したものである。 In other words, the results of Experiment 4 showed that in the presence of lysolecithin, lymphocytes from healthy individuals effectively fused with leukemia cells, strongly deformed and destroyed the leukemia cells, and
It is shown to eliminate tumor cells. However, because lysolecithin has a strong hemolytic effect,
It cannot be administered to humans as is. Therefore, the present inventor separately focused on the fact that by administering pantethine or a combination of pantethine and lecithin to healthy individuals, the body itself increases lysolecithin within the body's tolerance range, and has successfully applied this effect to the treatment of leukemia. It is.
以下実施例を挙げて説明する。 This will be explained below with reference to examples.
実施例 1
健康人にパンテチン1000mgをキシリトール20ml
に溶解して静脈内投与し、2時間後に採血し、こ
の血液と白血病患者の血液を1:1の割合で混
じ、37℃にて2時間保温した後実験例と同様の観
測の結果、白血病細胞の74%が変形破壊されるこ
とを確認した。Example 1 1000mg of pantethine and 20ml of xylitol in a healthy person
The blood was collected 2 hours later, mixed with the blood of a leukemia patient at a ratio of 1:1, and kept warm at 37°C for 2 hours. As a result of the same observation as in the experimental example, leukemia was detected. It was confirmed that 74% of the cells were deformed and destroyed.
このことは、パンテチン投与により生体内の酵
素であるレシチンコレステロールアシルトランス
フエラーゼ活性が増大し、これにより生体内でリ
ゾレシチンが生成し(特公昭55−2279)、本物質
が健康人リンパ球と白血病細胞との融合を促進
し、白血病細胞が変形破壊されたことを示すもの
である。 This indicates that administration of pantethine increases the activity of lecithin cholesterol acyltransferase, an enzyme in the body, which produces lysolecithin in the body (Special Publication No. 55-2279). This promotes fusion with cells and indicates that leukemia cells have been deformed and destroyed.
実施例 2
健康人にパンテチン静脈内投与と同時にレシチ
ン5gを経口投与し2時間後に採取した血液と白
血病患者の血液とを1:1の割合で混合し観測の
結果、変形破壊された白血病細胞は89%にも至つ
た。このことは、生体内の酵素であるレシチンコ
レステロールアシルトランスフエラーゼ活性が増
大し、しかもこの酵素の基質であるレシチンが存
在するため、より多くのリゾレシチンが生成し、
細胞融合がより強く促進されたことを示すもので
ある。Example 2 5 g of lecithin was orally administered to a healthy person at the same time as intravenous administration of pantethine, and blood collected 2 hours later was mixed with the blood of a leukemia patient at a ratio of 1:1. As a result of observation, leukemia cells that had been deformed and destroyed were It reached 89%. This means that lecithin cholesterol acyltransferase activity, which is an enzyme in the body, increases and lecithin, which is a substrate for this enzyme, is present, so more lysolecithin is produced.
This shows that cell fusion was more strongly promoted.
以上の成績から、パンテチンを単独投与、また
はパンテチンとレシチンを併用投与した健康人の
血液は、白血病細胞を強く変形破壊する作用を持
ち、したがつて、この健康人血液を白血病患者に
輸血することにより白血病の治療が行えることは
確実である。 From the above results, the blood of healthy people administered with pantethine alone or in combination with pantethine and lecithin has the effect of strongly deforming and destroying leukemia cells, and therefore, it is recommended that this blood of healthy people be transfused to leukemia patients. It is certain that leukemia can be treated with this method.
尚、治療に際しての輸血量と頻度は患者の症状
によつても異るが、通常250〜500ml/1回成人、
数回の投与で効果が期待される。 The amount and frequency of blood transfusion during treatment varies depending on the patient's symptoms, but it is usually 250 to 500 ml/time for adults,
It is expected to be effective after several doses.
本発明の目的遂行のためのパンテチンの投与量
は1回1000mgを静脈内投与、およびレシチンは5
gを経口投与したが、個人差もあり、パンテチン
では、通常、脂質代謝障害の治療に用いられてい
る量から2000mg以下程度の投与量で適宜増減され
るべきものであり、またレシチンでは、通常、動
脈硬化の治療に用いられている量から7.5g以下
程度の量で適宜増減さるべきものであろう。又、
両物質とも投与ルートとしては、経口、注射等特
に限定さるべき要因はなく、通常の薬剤投与と何
ら変るところはない。 The dosage of pantethine for achieving the purpose of the present invention is 1,000 mg intravenously, and the amount of lecithin is 1,000 mg.
However, there are individual differences, and for pantethine, the dosage should be adjusted as appropriate to about 2000 mg or less from the amount normally used for the treatment of lipid metabolism disorders. The amount should be adjusted as appropriate to 7.5 g or less from the amount used for the treatment of arteriosclerosis. or,
There are no particular limitations on the route of administration for both substances, such as oral or injection routes, and there is no difference from normal drug administration.
健常人にパンテチン又はパンテチンとレシチン
を投与すると生体内でリゾレシチンが生成し、投
与1〜4時間後、特に2〜3時間後にリゾレシチ
ンの血中濃度が最高に達するので、この時期に血
液を採取する。 When pantethine or pantethine and lecithin is administered to a healthy person, lysolecithin is produced in the body, and the blood concentration of lysolecithin reaches its maximum 1 to 4 hours, especially 2 to 3 hours after administration, so blood should be collected at this time. .
Claims (1)
〜4時間後に採取した健常人血液製剤からなる白
血病治療剤。 2 血液製剤が生体由来のリンパ球及びリゾレシ
チンを有効成分として含有することを特徴とする
特許請求の範囲第1項の白血病治療剤。[Claims] 1. Pantethine or pantethine and lecithin administration 1
A leukemia therapeutic agent consisting of blood products from healthy individuals collected after ~4 hours. 2. The therapeutic agent for leukemia according to claim 1, wherein the blood product contains lymphocytes derived from a living body and lysolecithin as active ingredients.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP56204135A JPS58105922A (en) | 1981-12-17 | 1981-12-17 | Remedy for leukemia |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP56204135A JPS58105922A (en) | 1981-12-17 | 1981-12-17 | Remedy for leukemia |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS58105922A JPS58105922A (en) | 1983-06-24 |
| JPH0149129B2 true JPH0149129B2 (en) | 1989-10-23 |
Family
ID=16485410
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP56204135A Granted JPS58105922A (en) | 1981-12-17 | 1981-12-17 | Remedy for leukemia |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS58105922A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3357512A4 (en) | 2015-09-29 | 2019-05-29 | Osaka University | PROMOTER OF LEUKOCYTE INFILTRATION AND IMMUNO-ACTIVATOR OF TUMORS |
-
1981
- 1981-12-17 JP JP56204135A patent/JPS58105922A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS58105922A (en) | 1983-06-24 |
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