U.S. patent application number 09/998429 was filed with the patent office on 2002-05-30 for interleukin-12 inducer and medical composition.
Invention is credited to Yagita, Akikuni.
Application Number | 20020064522 09/998429 |
Document ID | / |
Family ID | 18066096 |
Filed Date | 2002-05-30 |
United States Patent
Application |
20020064522 |
Kind Code |
A1 |
Yagita, Akikuni |
May 30, 2002 |
Interleukin-12 inducer and medical composition
Abstract
A pharmaceutical composition comprising activated hemicellulose
(AHCC), a method for inducing IL-12 in a living body having tumor
cells by administering the composition, and a method for treating
cancer by administering the composition are provided.
Inventors: |
Yagita, Akikuni; (Tokyo,
JP) |
Correspondence
Address: |
SUGHRUE MION, PLLC
2100 Pennsylvania Avenue, NW
Washington
DC
20037-3213
US
|
Family ID: |
18066096 |
Appl. No.: |
09/998429 |
Filed: |
December 3, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09998429 |
Dec 3, 2001 |
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09447049 |
Nov 23, 1999 |
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09447049 |
Nov 23, 1999 |
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08967821 |
Nov 12, 1997 |
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Current U.S.
Class: |
424/93.44 ;
424/195.15; 514/57 |
Current CPC
Class: |
A61K 36/06 20130101;
A61K 35/744 20130101; A61K 36/07 20130101; A61K 36/074 20130101;
A61K 36/06 20130101; A61K 35/744 20130101; A61P 43/00 20180101;
A61K 31/717 20130101; A61K 36/07 20130101; A61K 36/074 20130101;
A61P 35/00 20180101; A61K 2300/00 20130101; A61K 2300/00 20130101;
A61K 2300/00 20130101; A61K 2300/00 20130101 |
Class at
Publication: |
424/93.44 ;
424/195.15; 514/57 |
International
Class: |
A61K 035/84; A61K
031/717 |
Foreign Application Data
Date |
Code |
Application Number |
Nov 11, 1996 |
JP |
HEI. 8-315498 |
Claims
What is claimed is:
1. A pharmaceutical composition comprising activated hemicellulose
as an active ingredient in an amount effective to induce
interleukin-12 and a pharmaceutically acceptable carrier.
2. The pharmaceutical composition as claimed in claim 1, which
further contains components of fungal mycelium.
3. The pharmaceutical composition as claimed in claim 2, which
further contains bacterial components of hemolytic
streptococci.
4. A method for inducing interleukin-12 in vivo, comprising
administering a pharmaceutical composition containing activated
hemicellulose as an active ingredient and a pharmaceutically
acceptable carrier.
5. The method for inducing interleukin-12 in vivo as claimed in
claim 4, wherein said pharmaceutical composition further contains
components of fungal mycelium.
6. The method for inducing interleukin-12 in vivo as claimed in
claim 5, wherein said pharmaceutical composition further contains
bacterial components of hemolytic streptococci.
7. A method for treating cancer, comprising administering a
pharmaceutical composition containing activated hemicellulose
(AHCC) as an active ingredient and a pharmaceutically acceptable
carrier by a single or simultaneous use in an amount which can
induce interleukin-12 in vivo.
8. The method for treating cancer as claimed in claim 7, wherein
said pharmaceutical composition further contains components of
fungal mycelium.
9. The method for treating cancer as claimed in claim 8, wherein
said pharmaceutical composition further contains bacterial
components of hemolytic streptococci.
10. The pharmaceutical composition according to claim 1, further
comprising shark cartilage.
11. The method according to claim 4, further comprising
administering shark cartilage.
12. The pharmaceutical composition as claimed in claim 1, wherein
the activated hemicellulose is selected from the group consisting
of a .beta.-D-glucan and an .alpha.-D-glucan.
13. The pharmaceutical composition as claimed in claim 1, wherein
the activated hemicellulose is a mixture of a .beta.-D-glucan and
an .alpha.-D-glucan.
14. The method for inducing interleukin-12 in vivo as claimed in
claim 4, wherein the activated hemicellulose is selected from the
group consisting of a .beta.-D-glucan and an .alpha.-D-glucan.
15. The method for inducing interleukin-12 in vivo as claimed in
claim 4, wherein the activated hemicellulose is a mixture of a
.beta.-D-glucan and an .alpha.-D-glucan.
16. The method for treating cancer as claimed in claim 7, wherein
the activated hemicellulose is selected from the group consisting
of a .beta.-D-glucan and an .alpha.-D-glucan.
17. The method for treating cancer as claimed in claim 7, wherein
the activated hemicellulose is a mixture of a .beta.-D-glucan and
an .alpha.-D-glucan.
Description
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention relates to a substance that can induce
interleukin-12 in vivo, and to a medical composition containing the
same.
[0003] 2. Description of the Related Art
[0004] Interleukin-12 (IL-12) was originally found as one of
cytokinins that can activate NK cells. Subsequent studies revealed
that it also promoted growth of and activated T cells that had
cytotoxicity specific to tumor cells (Killer T cells), and further
it promoted the production of interferon .gamma.(IFN .gamma.) that
stimulated activation of killer T cells. Thus IL-12 has attracted
attention as a substance effective in treating human cancer
patients.
[0005] Recently, large-scale production of IL-12 by using a gene
manipulation technique was realized in the U.S. (Recombinant IL-12
(rt-IL-12)). Following that, in order to directly deliver IL-12 to
cancer cells, a method for directly introducing the IL-12 producing
gene into tumor cells, by using gene introduction techniques, has
been investigated.
[0006] However, sensitivity of rt-IL-12 used in the method is low
and administration of a large-amount is needed, for example, to
treat human cancer. Such large-amount dosage causes various side
effects including fever and inappetence. Besides these serious side
effects, several problems regarding this method are pointed out,
that is, the gene manipulation procedure is so complicated that it
is labor intensive and lacks economical feasibility.
[0007] For using IL-12 to prevent tumor growth or cause regression,
there are two methods; one is to externally administrate IL-12, and
the other is to induce in vivo production of IL-12. Such induced
IL-12 does not raise abnormal immune response, thereby resolving
intrinsic problems of rt-IL-12. At the same time, such IL-12 is
highly effective, thus extensive tumor loss regression effect can
be expected. However, before the instant invention an effective
substance that could induce IL-12 of its own in vivo had not been
found.
SUMMARY OF THE INVENTION
[0008] In view of the above circumstances, it is an object of the
present invention to provide a method for inducing IL-12 in vivo in
a tumor bearing patient and a substance having such an induction
effect, and further to provide a medical composition obtained by
utilizing the same.
[0009] According to the present invention, there is provided an
interleukin-12 inducer containing activated hemicellulose (AHCC)
and a medical composition containing the same.
DETAILED DESCRIPTION OF THE INVENTION
[0010] Hereunder, the detailed description is made of the present
invention.
[0011] Activated HemiCellulose Compound (AHCC) of the present
invention is a known compound as a biologically active substance
which is obtained by enzyme treatment of plant fiber existing in
the cell wall of fungal mycelia. Preferable AHCCs for use in the
present invention are selected from (1) .beta.D-glucan, (2)
.alpha.-D-glucan, and (3) a mixture of .beta.D-glucan and
.alpha.-D-glucan. AHCC contains in addition to heteroglucan such as
.beta.-(1-3)D-glucan, .beta.-(1-6)D-glucan and
.alpha.-(1-4)D-glucan; peptidoglycan, proteoglucan, lectin, nucleic
acid and indigestive polysaccharide. Dojin News, No. 34, pages 2-4
(1985); the entire content of which is hereby incorporated by
reference.
[0012] However, it had not been previously known that AHCC could
induce IL-12, until the fact was newly found by the present
inventor.
[0013] The IL-12 inducer of the present invention may consist only
of the above described AHCC, but preferably further contains
components of fungal mycelium (Eubasido-mycetes). Examples of such
components of mushroom's mycelium include PSK that is a component
of a polypore's mycelium (Polyporacede) and used as a known
anti-cancer agent, SPG that is a component of Schizophyllum commune
mycelium's mycelium, and lentinan that is a component of a
shiitake's mycelium (Lentinula edodes), but are not limited
thereto.
[0014] Further, such components of fungal mycelium include, for
example, that of agarisku, Ganoderma lucidum, ningyotake,
kawariharatake, niousimeji, kabenoanatake, Griforia frondosa,
Hericium erinaceum, an oyster fungal (Pleurotus ostreatus),
mannnenntake (Ganoderma lucidum), Panellus serotinus, kobutake,
Lenzites betulina, a matsu-take (Tricholoma matsutake), bekkoutake,
nametake and Frammulina velutipes.
[0015] The IL-12 inducer of the present invention may be composed
of only above described AHCC and components of fungal mycelium, but
preferably contains bacterial components of hemolytic streptococci
in addition to the above. Examples of such bacterial components of
hemolytic streptococci include, OK-432 that is a known anti-cancer
agent, but are not limited thereto.
[0016] These are known substances as biological response modifiers
(BRMs).
[0017] It has been revealed that in progressed cancer or end-stage
cancer, tumor regression or disappearance could not be obtained by
established conventional treatments of modern medicine such as
surgery, administration of an anti-cancer agent, radiotherapy and
hormonotherapy. On the other hand, the IL-12 inducer of the present
invention is effective for tumor regression and disappearance in
progressed or end-stage cancer. Effectiveness can be determined by,
for example, assay of body fluid or parts, NMR, surgery or
palpitation. This fact was newly discovered by the present
inventor. This is the first unique effect of the present
invention.
[0018] No side effects were found in the administration of the
IL-12 inducer of the present invention. Rt-IL-12 produced by the
conventional gene manipulation method has low sensitivity and
therefore requires administration in a large volume, which often
induces various side effects and exerts upon patients serious
damage. On the other hand, the reason why there is no concern for
side effects, is because the IL-12 inducer of the present invention
can activate the IL-12 production ability naturally existing in a
living body as its basic action mechanisms, it is not necessary to
externally administer a substance causing side effects.
[0019] This fact is newly found by the present inventor and is the
second unique effect of the present invention.
[0020] The medical composition of the present invention contains
the above described IL-12 inducer as the main component. The
medical composition of the present invention can be used, for
example, as an anti-cancer agent but not limited thereto.
[0021] The formulation of the medical composition of the present
invention to be administered to a human or animal is not
specifically limited. The medical composition of the present
invention may be, for example, retained on carriers and suitably
prepared into various formulations commonly used in medicine.
[0022] As such carriers, at least one selected from solid,
semi-solid or liquid diluent, filler and other support for
formulation may be used at a ratio of for example, 0.1% to 99.5%,
preferably 0.5% to 90%. The medical composition of the present
invention may be safely administered perorally or parenterally. The
route of parenteral administration includes local administration
such as intratissue administration, subcutaneous administration,
intramuscular administration, intra arterial/intravenous
administration and per rectum administration. Formulations suitable
for the above administration routes may be prepared using known
practical means.
[0023] For example, when used as an anti-cancer agent, the dosage
is preferably determined according to age, body weight,
administration route used, type of disease and severity. In the
case of administration for human patients, it is, for example,
generally administered perorally at a dosage of 100 to 20,000
mg/day as the active compound, preferably 1,000 to 10,000 mg/day as
the active compound. For parenteral administration, the dosage
largely differs according to the administration route, but in
general, 100 to 1,000 mg/day, preferably 200 to 500 mg/day may be
used. According to each case, a lower dosage may be enough, or a
larger dosage may be required. Dosage can be divided into two to
four doses per day. Depending on the patient and specific
constituents of the anticancer formulation, the effective dose
range may vary. Tumor stasis or regression or other clinical
indicators can be used to determine an appropriate dose.
[0024] For peroral administration, solid or liquid formulation may
be used such as pulvis, powder, granule, tablet, capsule, syrup,
elixir and suspension.
[0025] Pulvis is prepared by pulverizing the active substance to
suitable fineness. Powder is prepared by pulverizing the active
substance to suitable fineness, and then mixing it with medical
carrier prepared to the same fineness, for example, dietary
carbohydrate such as starch and mannitol, and other vehicles. If
necessary, a corrective, preservatives, dispersing agent, tinction,
aromatic and others may be added therein.
[0026] Capsule is prepared by filling the above described
pulverized pulvis, powder or granulated tablets into an outer
capsule, for example, a gelatin capsule. Before filling, lubricant
or drifting agent, for example, colloidal silica, talc, magnesium
stearate, calcium stearate and solid polyethylene glycol may be
arbitrarily mixed therein. Efficacy of medicine in capsule
formulation after intake is improved by adding therein a
disintegrator or solubilizing agent such as carboxymethyl
cellulose, calcium carboxymethyl cellulose, low-substituted
hydroxypropyl cellulose, sodium crosskarumelose, sodium
carboxystarch, calcium carbonate and sodium carbonate.
[0027] Soft capsule may be prepared by suspending fine powders of
the present product in plant oil, polyethylene glycol, glycerin,
and a surfactant and encapsulate them within gelatin sheet.
[0028] Granules may be prepared by mixing the pulverized active
substance and above described vehicle, a disintegrator and, if
necessary, binder (for example, sodium carboxymethyl cellulose,
hydroxypropyl cellulose, methyl cellulose, hydroxypropylmethyl
cellulose, gelatin, polyvinylpyrrolidone, polyvinylalchol, and the
like), humectant (for example, syrup, starch, gum arabic, cellulose
solution, macromolecule solution, and the like), kneading them, and
letting them pass through a sieve. Alternative to granulate
powders, granule may be obtained by pulverizing slug of
insufficient shapes which had raised at tableting. Dissolution
delaying agent (for example, paraffin, wax, hardened castor oil,
and the like), a reabsorption agent (for example, quaternary salts
or the like) or adsorbent (for example, bentonite, Kaolin,
dicalcium phosphate, and the like) may be mixed therewith in
advance.
[0029] Tablets may be prepared by adding lubricant including
stearic acid, stearate, talc, mineral oil, and the like to thus
obtained granules and then tableting. Thus obtained intact tablets
may be covered with film coating or sugar coating.
[0030] The mixing process of the active substance of the present
invention and fluid inactive carrier may be immediately followed by
the tableting process without above described granulation process
or slug process. Coatings that can be used include transparent or
semi-transparent protect coating of closed coating of shellac,
coating of sugar or macromolecules and finish coating consisting of
wax.
[0031] Other peroral formulation, including syrup, elixir and
suspension can be prepared in dosage per unit so that a
predetermined amount of the medical substance is contained in a
predetermined amount of each formulation. Syrup may be prepared by
dissolving the active agent in a suitable flavored water solution.
Elixir may be prepared by using non-toxic alcoholic carrier.
Suspension may be prepared by dispersing the active substance in
non-toxic carriers. A suspending agent or emulsifier (for example,
ethoxylated isostearyl alcohols and polyoxyethylene sorbitol
esters), preservative, corrective (for example, peppermint oil and
saccharin) and other agents may be arbitrarily added thereto.
[0032] If necessary, the dosage unit for peroral administration may
be contained in microcapsules. In this method, the active substance
is coated or buried in macromoleculars or wax, thereby prolonging
action time or delaying the release.
[0033] Subcutaneous, intramuscular, intra-arterial and intravenous
administration can be given by using liquid dosage unit
formulation, for example injection consisting of solution or
suspension. These formulation is prepared by dissolving or
suspending a predetermined amount of the active substance in
non-toxic liquid carrier suitable for objective injection route
including aqueous or oleaginous solvent and then sterilizing the
solution or suspension. Alternatively, a predetermined amount of
the powder or freeze-dried active substance may be placed in a vial
and the vial and contents thereof may be sterilized and sealed. In
this case, the active substance is to be dissolved or mixed
immediately before the administration, and spare vials or carriers
can be reserved. Non-toxic salts or salt solution to prepare an
isotonic injection may be added and further a stabilizer,
preservative, suspending agent emulsifier and others may be
combinedly used.
[0034] The formulation for per rectal administration may be
prepared by mixing the active substance with hydrophobic or
hydrophilic suppository base including, for example, polyethylene
glycol, cacao butter, higher esters (for example, myristyl ester of
palmitic acid) and mixture thereof.
[0035] AHCC, components of fungal mycelium, and bacterial
components of hemolytic streptococci of the present invention have
the effect of inducing IL-12. Accordingly, a method of inducing
IL-12 in vivo by administering these substances is within the scope
of the present invention.
[0036] Further, AHCC, components of fungal mycelium, and bacterial
components of hemolytic streptococci of the present invention have
the effect to induce IL-12. Accordingly, a method to cure cancer by
administering them in single or multiple administration at a dose
that can induce IL-12 is within the scope of the present
invention.
EXAMPLES
[0037] The present invention may be better illustrated with
reference to the following examples. However, the present invention
is not limited thereto.
Example 1
[0038] Example of single administration of AHCC
[0039] A human patient suffering from esophagus cancer (72-
year-old, male) showing infiltration at cervical lymph nodes and
intraperitoneal lymph nodes, no indication for surgery,
unresponsive to radiotherapy, unable to perform oral intake of
other than water.
[0040] To this patient, AHCC was continuously administered at a
dosage of 3.0 g/day. One month after the start of the
administration, the patient became able to eat 30% gruel or 50%
gruel. The level of serum SCC tumor marker was 23 ng/mL before the
administration (normal level: 2.0 ng/mL), but improved to 1.3 ng/mL
one month after. By further continuing the administration, he
became able to eat 100% gruel three months after the administration
commencement, when the tumor was confirmed to have completely
disappeared by fluoroscopic and CT examinations of esophagus.
[0041] After a three-month administration of AHCC, serum NK
activity was as high as 68% (normal value: lower than 40%), and
serum IL-12 level was also as high as 78 pg/mL (normal value: lower
than 7.2 pg/mL). These result are listed in Table 1.
[0042] In Table 1, CD4 represents helper T cells, and CD8
represents killer T cells. The CD4/CD8 ratio represents degree of
increase in killer T cells, and a value less than 1 represents
increase in killer T cells. The range of normal values is 1.0 to
1.5. The CD4/CD8 ratio in Example 1 was 0.75, showing that
cytotoxic killer T cells was increased.
Example 2
[0043] Example of single administration of AHCC
[0044] In a human patient suffering from orchioncus (36- year-old,
male), primary cancer in the right testis was excised. After the
surgery, metastasis of an infant's head size to a peritoneal lymph
node occurred. AHCC at a dosage of 3.0 g/day was continuously
administered orally to this patient. After one month, the size of
tumor decreased approximately by half, and after three months, the
tumor completely disappeared.
[0045] After three months administration, NK activity was low at
13%, but IL-12 level was extremely high at 120 pg/mL. It was
suggested that the anti-tumor effect of AHCC was not through NK
activity. These results were listed in Table 1.
1 TABLE 1 Serum CD4/ Human NK IL-12 Treatment CD8 patient Symptoms
Activity level evaluation ratio Ex- 72-year- esophagus 68% 78 CR;
0.75 am- old; cancer; surgery ng/mL complete ple male impossible;
regression 1 unresponsible; end-stage cancer Ex- 36-year- right
testis 13% 120 CR 0.52 am- old; tumor; infant's ng/mL complete ple
male head size regression 2 metastasis to retroperitoneal lymph
node; end-stage cancer
Examples 3 to 6
[0046] Examples of combined administration of AHCC with shark
cartilage
[0047] To the human cancer patients listed in Table 2, AHCC at a
dosage of 3.0 g/day and concomitantly shark cartilage (.beta.
shark) at 20 g/day were continuously administered orally. After
three months administration, treatment evaluation and NK Activity,
IL-12 level and CD4/CD8 ratio were evaluated.
[0048] According to Examples 3 and 6, tumor regression of 50% or
more was obtained in either case. However, the NK activity in
either example was within the normal range, indicating that the NK
activity was not elevated. In either of Examples 3 to 6, the IL-12
level was high significantly exceeding the normal range. It was
suggested that IL-12 was involved in tumor regression. Further,
from the results of previous immunological investigations, it has
been shown that concomitant use of shark cartilage had no effect on
the NK activity and did not elevate the IL-12 level.
2 TABLE 2 Serum Human NK IL-12 Treatment CD4/CD8 patient Symptoms
activity level evaluation ratio Example 72- stomach 24% 240 ng/mL
CR 0.34 3 year- cancer; complete old; progressed regression male
stage Example 57- caecum 62% 230 ng/mL CR 0.42 4 year- cancer;
complete old; carcinomatous regression male peritonitis; end-stage
cancer Example 69- stomach 62% 103 ng/mL CR 0.62 5 year- cancer;
complete old; metastasis to regression male liver; end-stage cancer
Example 71- hepatic 68% 78 ng/mL PR; 6 year- cancer; metastasis
old; metastasis to disappear female lung- end-stage cancer
Examples 7 and 8
[0049] Examples of combined administration of AHCC, PSK and shark
cartilage
[0050] To the human cancer patients listed in Table 3, first,
continuous oral administration of AHCC at a dosage of 3.0 to 6.0
g/day combined with shark cartilage at a dosage of 20 g/day. Until
three months, tumor regression was not found and the IL-12 level
was not elevated.
[0051] Then, to the human cancer patients listed in Table 3, in
addition to the continuous oral administration of AHCC at a dosage
of 3.0 to 6.0 g/day combined with shark cartilage at a dosage of 20
g/day, PSK (Sankyo Co. Ltd., Krestin) at 3.0 g/day was further
combinedly administered. After addition of PSK administration, the
IL-12 level was elevated and at the same time, partial regression
(PR) effect of 50% or higher for tumor was obtained.
[0052] It was shown that concomitant use of shark cartilage had no
effect on the NK activity and did not elevate the IL-12 level.
Further, since single administration of PSK at 3.0 g/day had not
shown a regression effect for lung tumor, the observed regression
effect was thought to be achieved by the concomitant use of AHCC
and PSK. It was suggested that PSK also promoted the IL-12
production.
3 TABLE 3 Serum Human NK IL-12 Treatment CD4/CD8 patient Symptoms
activity level evaluation ratio Example 67- left lung 32% 240 ng/mL
PR; 0.43 7 year- cancer; right lung old; metastasis to metastasis
male right lung; disappear metastasis to liver- end-stage cancer
Example 73- right lung 29% 340 ng/mL PR; 0.43 8 year- cancer; lung
old; metastasis to metastasis female left lung; disappear
metastasis to liver end-stage cancer
Comparative Examples 1 and 2
[0053] Examples of concomitant use of OK-432, PSK and SPG (or
Lentinan)
[0054] As shown in Table 4, the effect of multiple immunotherapy
was tested in Comparative example 1, by subcutaneous administration
of OK-432 (Chugai Pharmaceutical Co. Ltd., Picibanil) at a dosage
of 5 KE/W, oral administration of PSK (Sankyo Co. Ltd., Krestin) at
3.0 g/day and further intramuscular injection of SPG (Kaken
Pharmaceutical Co. Ltd., Sonifilan) at vial/W. In Comparative
Example 2, the effect of multiple immunotherapy was also tested in
the same manner as in Comparative Example 1, except that in stead
of SPG, Lentinan (Yamanouchi Pharmaceutical Co. Ltd., Lentinan) was
intravenously injected at 400 mg/w.
[0055] In either example, dramatic tumor regression was achieved.
Further, the IL-12 level was high in either example. It was
suggested that the anti-cancer effect obtained by the multiple
immunotherapy may be due to the increased production of IL-12.
4 TABLE 4 Serum Human NK IL-12 Treatment CD4/CD8 patient Symptoms
activity level evaluation ratio Comparative 23- stomach 32% 240
ng/mL CR 0.72 example 1 year- cancer; complete old; carcinomatous
regression male peritonitis; end-stage cancer Comparative 72-
hepatic 40% 260 ng/mL PR 3/4 0.32 example 2 year- cancer; of old;
carcinomatous hepatic male peritonitis cancer end-stage disappear-
cancer ance
[0056] For patients with progressed cancer or end-stage cancer,
example in which tumor regression or disappearance was achieved by
administering BRM preparation to induce the IL-12 production has
not been previously reported. This was newly found by the present
inventor. It was clarified that the observed effect was not only
mediated by the NK activity but also by the induction of IL-12 and
an increase of killer T cells. It was also found that when
anti-cancer effect is to be enforced by induction of IL-12,
concomitant administration of shark cartilage that inhibits
neovascularization was also effective.
[0057] Furthermore, it was found that additional PSK administration
was effective to promote anti-cancer effect of AHCC. This promotion
effect was especially remarkable in lung cancer, hepatic cancer,
stomach cancer, large intestine cancer, pancreatic carcinoma and
kidney cancer.
[0058] It was found that IL-12 could be induced by concomitant
administration of BRM preparations other than IL-12 or by
concomitant administration of three drugs of OK-432, PSK and SPG
(or Lentinan).
[0059] At present circumstances, even by making the most use of
treatments in the modern medicine, including surgery,
administration of anti-cancer agent, radiotherapy and
hormonotherapy, few effect can be expected in the treatment of
progressed cancer or end-stage cancer. Administration of an IL-12
inducer of the present invention or a medical composition
containing the same as the major component is highly effective in
the practical use, showing high efficacy in the treatment of the
progressed cancer or end-stage cancer or in the improvement of
QOL.
* * * * *