Process for producing a culture of Antrodia camphorata and product obtained thereby 机翻标题: 暂无翻译,请尝试点击翻译按钮。

公开号/公开日
US2003086908 A1 2003-05-08 [US20030086908] US6767543 B2 2004-07-27 [US6767543] / 2003-05-08 2004-07-27
申请号/申请日
2002US-10113903 / 2002-03-29
发明人
WU MEI-CHIAO; HUANG REN-CHANG; LIN SHIE-JEA; WANG BOR-CHEH
申请人
COUNCIL OF AGRICULTURE EXECUTI
主分类号
IPC分类号
A61K-035/12;C12N-001/14;C12P-001/02
摘要
(US6767543)
The present invention relates to the establishment of a cultivation condition that is suitable for the large-scale production of pharmacologically active filtrates from a culture of A. camphorata, in particular, by optimizing the agitation rate and/or pH value during the cultivation. 
The present invention also relates to a process for obtaining pharmacologically active compositions from a culture of A. camphorata through a series of fractionation. 
This invention is further directed to the uses of the above compositions in the preparation of pharmaceutical compositions.
机翻摘要
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地址
代理人
代理机构
优先权号
2000TW-0102716 2000-02-17 2000US-09566834 2000-05-08 2002US-10113903 2002-03-29
主权利要求
(US6767543)
1. A process for obtaining a pharmacologically active composition from a culture of Antrodia camphorata, comprising:
(a) preparing a first culture by inoculating a mycelial inoculum of an isolate of Antrodia camphorata into a medium suitable for the growth of said isolate;
(b) cultivating the first culture from step (a) for a period of time;
(c) harvesting a pharmacologically active solution by removing a major portion of insoluble substance from the cultivated culture of step (b);
 and
(d) subjecting the solution obtained from step (c) to selective separation based on molecular weight, such that a pharmacologically active composition containing fungus-produced compounds having molecular weights of no more than about 10 kDa is obtained.
We claim:
2. 
The process of claim 1, wherein the composition obtained in step (d) contains fungus-produced compounds having molecular weights of no more than about 3 kDa.
3. The process of claim 2, wherein the composition obtained in step (d) contains fungus-produced compounds having molecular weights of no more than about 1 kDa.
4. A process for obtaining a pharmacologically active composition from a culture of Antrodia camphorata, comprising:
(a) forming a first culture by inoculating a mycelial inoculum of an isolate of Antrodia camphorata into a medium suitable for the growth of said isolate;
(b) cultivating the first culture from step (a) for a period of time;
(c) harvesting a pharmacologically active solution by removing a major portion of insoluble compounds from the cultivated culture of step (b);
(d) subjecting the solution obtained from step (c) to selective separation based on molecular weight, such that a fraction containing fungus-produced compounds having molecular weights of no more than about 1 kDa is obtained;
 and
(e) subjecting the fraction obtained from step (d) to chromatographic separation based on polarity, such that a pharmacologically active composition containing fungus-produced compounds that are hydrophobic is obtained.
5. The process of claim 4, wherein the chromatographic separation step (e) is conducted by passing through a stationary water-immiscible phase that contains an effective amount of an absorbent capable of selectively adsorbing hydrophobic fungus-produced compounds, and the pharmacologically active composition is obtained by eluting the stationary water-immiscible phase with an organic solvent.
6. The process of claim 5, wherein the stationary water-immiscible phase comprises Amberlite  (Registered trademark)  XAD-4 resins as the absorbent.
7. The process of claim 5, wherein in the selective separation step (e), an organic solvent having a polarity lower than water is used to elute the stationary water-immiscible phase.
8. The process of claim 7, wherein the organic solvent has polarity lower than methanol.
9. The process of claim 8, wherein the organic solvent is selected from the group consisting of ethyl acetate and ethanol.
10. The process of claim 4, further comprising:
(f) subjecting the composition obtained in step (e) to a reverse-phase partition chromatography to obtain pharmacologically active fractions.
11. The process of claim 1, wherein the pharmacologically active composition obtained from step (d) has an activity in inhibiting the growth of tumor or cancer cells.
12. The process of claim 4, wherein the pharmacologically active composition obtained from step (d) has an activity in inhibiting the growth of tumor or cancer cells.
13. The process of claim 10, wherein the pharmacologically active fractions obtained from step (f) have an activity in inhibiting the growth of tumor or cancer cells.
14. The process of claim 1 or 4, wherein the cultivating step (b) includes the following sub-steps:
(i) subjecting the first culture obtained in step (a) to a first stage of agitation which is set at a first predetermined rate and for a first period of time to allow growth of the inoculated isolate, such that a second culture with proliferated mycelia is obtained;
 and
(ii) subjecting the second culture obtained from step (ii) to a second stage of agitation which is set at a second predetermined rate different from the first predetermined rate, so that the isolate grown in the second culture is cultivated under physiological stress.
15. The process of claim 14, wherein the second predetermined rate used in sub-step (ii) is higher than the first predetermined rate used in sub-step (i).
16. The process of claim 14, wherein in the sub-steps (i) and (ii), the first culture obtained in step (a) and the second culture obtained from step (i) are cultivated at a pH value adjusted to range from 4.5 to 5.4, respectively.
17. The process of claim 16, wherein the first culture obtained in step (a) and the second culture obtained from step (i) are cultivated at a pH value adjusted to range from 4.6 to 5.3, respectively.
18. The process of claim 16, wherein the first culture obtained in step (a) and the second culture obtained from step (i) are cultivated at a pH value adjusted to range from 4.7 to 5.2, respectively.
19. The process of claim 1 or 4, wherein the Antrodia camphorata isolate is selected from the group consisting of CCRC 930032 (ATCC PTA-1233), CCRC 35396, CCRC 35398 and CCRC 35716.
20. The process of claim 1 or 4, wherein the medium used in step (a) is potato dextrose broth or a synthetic medium containing fructose as a major carbon source.
21. The process of claim 20, wherein the medium used in step (a) is a synthetic medium containing fructose as a major carbon source.
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(US6767543)
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