JPH0236126A - Agent for protecting from radiation injury - Google Patents

Abstract

PURPOSE:To provide the subject radiation injury protecting agent effective in promoting the natural protecting function of a living body by using an active component comprising a nonapeptide, its derivative and its salt having high safety, originated from nature and known as a serum thymic factor. CONSTITUTION:The objective preventive or remedy for protecting a body from various injury caused by X-ray, gamma-ray, ultraviolet ray, etc., contains, as an active component, a nonapeptide having the amino acid sequence of formula, its ester at the carboxyl group of the C-terminal asparagine, its amide or their pharmacologically permissible salts. The radiation dose applicable to the diseased part in radiotherapy can be remarkably increased by the use of the protecting agent and the hemopoietic function disorder caused by the radiation can be restored by this agent.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a novel pharmaceutical for humans or animals, and more specifically, it relates to a drug or a drug that has a protective effect against various radiation-induced disorders. The present invention relates to a drug that promotes recovery from hematopoietic dysfunction caused by radiation irradiation.

[Background technology]

In recent years, damage caused by radiation such as high-energy X-rays, gamma rays, electromagnetic waves, or cosmic rays used for medical purposes, as well as ultraviolet rays contained in sunlight, has increased, especially due to radiation therapy used for malignant tumors, cancer, and leukemia. The problems it causes are viewed as a problem. Radiotherapy, along with surgery, is a fundamental cancer treatment method, but the early appearance of disorders in patients due to radiation exposure has weakened the evaluation and expectations for the usefulness of radiotherapy. Early disorders include hematopoietic dysfunction, local disorders such as fibrosis that occurs in organs, skin, and mucous membranes, and gastrointestinal disorders, but reducing and recovering from hematopoietic dysfunction is particularly important for improving patient prognosis and prolonging life. is required.

If we can develop preventive and therapeutic agents that can protect against the various disorders caused by radiation irradiation, it will be possible to dramatically increase the amount of radiation that can be irradiated to the affected area during radiation therapy, further increasing the effectiveness of radiation therapy for cancer. can contribute to this.

These include early effects of radiation such as skin erythema and pigmentation, late effects such as radiation burns on the skin, hematopoietic dysfunction, accelerated aging, and shortened lifespan, and especially secondary effects caused by radiation therapy. How to protect patients from the risk of carcinogenesis is an important issue.

In addition, radiation exposure of radiation handlers and nuclear reactor workers, and 7
There are concerns that the number of cancer patients will increase due to genetic effects and carcinogenic effects due to exposure to more powerful ultraviolet rays due to the depletion of the ozone layer in the upper atmosphere due to atmospheric gases.

Human skin is sensitive to ultraviolet rays in the wavelength range of 280 to 320 nm, and in particular, ultraviolet rays in the 305 to 310 nm+ range are said to cause skin cancer. It has been argued that the destruction of the ozone layer, which absorbs ultraviolet rays in this wavelength range, increases the amount of ultraviolet rays that fall on the ground, leading to an increase in skin cancer as mentioned above.
Developing drugs to prevent and treat such radiation exposure disorders has also become an important issue.

Although fused amine compounds and the like have been studied as drugs to protect living bodies from radiation exposure, they have not yet been clinically applied. Recently, as a radiation protection agent,
In the United States, Am1fostine (Waiter Ree
d Army In5t) is currently undergoing clinical trials, but there are problems with side effects.

[Disclosure of the invention]

The present inventors have developed various highly safe naturally derived peptides with the aim of developing a drug that enhances the body's natural defense ability, which is different from chemotherapeutic agents such as Am1fostine. We have actively searched for substances that are useful as prophylactic and therapeutic agents for protecting against radiation damage.

As a result, serum thymi
We have found that a nonapeptide (hereinafter abbreviated as FTS) known as queser 1que (hereinafter abbreviated as FTS) and its derivatives or salts thereof reliably prevent the death of X-ray irradiated mice and prolong their survival. The present invention was made based on this knowledge, and provides a preventive/therapeutic agent for protecting against various disorders caused by X-rays, γ-rays, ultraviolet rays, and the like.

The present inventors have previously demonstrated that FTS is suitable as a therapeutic agent for various diseases associated with immunodeficiency, such as multiple sclerosis, Guillain-Barre syndrome, inflammatory neuritis, multiple sclerosis, and other immune-mediated demyelinating diseases. They discovered that the nonapeptide known as FTS is effective in preventing radiation damage and providing such a therapeutic agent (Japanese Unexamined Patent Publication No. 58-52225).
The fact that it has a healing effect is completely unexpected from the prior art and was discovered for the first time by the present inventors. Thus, the present invention provides a nonapeptide pGlu-Ala-Lys-Ser-Gln-Gly- having the following amino acid sequence:
This invention provides a radiation protection agent characterized by containing Gly-3er-Asn or an ester, amide, or a pharmaceutically acceptable salt thereof at the carboxyl group of asparagine at the C-terminus as an active ingredient. be.

The nonapeptide used in the present invention can be produced without difficulty by a liquid-phase or solid-phase pegutide synthesis method commonly used for peptide synthesis (
Regarding these methods, please refer to Japanese Patent Application Laid-Open No. 16425/1983, USP 4301065). Alternatively, it can also be prepared by genetic engineering or cell engineering techniques.

The ester at the carboxyl group of asparagine at the C-terminus of the nonapeptide used in the present invention is
Pharmaceutically acceptable esters of carboxylic acids, such as methyl ester, ethyl ester, propyl ester, isopropyl ester, n-butyl ester, isobutyl ester, tert,-butyl ester, n-pentyl ester, Impentyl ester, neopentyl ester, tert-pentyl ester,
n-hexyl ester, 5ec-hexyl ester, heptyl ester, octyl ester, 5ec-octyl ester, tert-octyl ester, nonyl ester, decyl ester, undecyl ester, dodecyl ester, tridecyl ester, tetradecyl ester,
Hexadecyl ester, octadecyl ester, nonadecyl ester, eicosyl ester, cyclopentyl ester, cyclohexyl ester, cycloheptyl ester, cyclooctyl ester, allyl ester, isopropenyl ester, benzyl ester, o-
m s also halo-chlorobenzyl ester, o-m-
1 or p-fluorobenzyl ester, o m- or p-bromobenzyl ester, o-, m- or p-iodobenzyl ester % O-m- or p-methylbenzyl ester, O-m- or p-ethyl benzyl ester, o-m- or p-inglovir benzyl ester, cinnamyl ester, aminoethyl ester, o-m-,
or p-aminobenzyl ester, 〇-m-1 or p-
Nitrobenzyl ester, 0-m-1 or p-methoxybenzyl ester, 0m-1 or p-ethoxybenzyl ester, o-, m+, or p-amino 7enethyl ester, α-furfuryl ester, a-thienylmethyl ester, α-pyridyl methyl ester, α-pyridylethyl ester, piperidinomethyl ester, α-hepiperidyl methyl ester, morpholinoethyl ester, α-
Examples include morpholinyl methyl ester.

Further, the amide in the carboxyl group of asparagine at the C-terminus of the nonapeptide used in the present invention is a pharmaceutically acceptable carboxylic acid amide,
Examples include amide, methylamide, ethylamide, propylamide, isopropylamide, n-butyramide, isobutyramide, tart-butyramide, n
-Pentylamide, isopentylamide, neopentylamide, Iert-pentylamide, n-hexylamide, 5ec-hexylamide, heptylamide, octylamide, 5ec-octylamide, tert-octylamide, nonylamide, decylamide, undecylamide , dodecylamide, tridecylamide, tetradecylamide, hexadecylamide, octadecylamide,
nonadecylamide, eicosylamide, cyclopentylamide, cyclohexylamide, cyclohebutylamide, cyclooctylamide, allylamide, impropenylamide, benzylamide, Q m -, or p-
Chlorobenzylamide, o-m-5 or p-fluorobenzylamide, o-m+, or p-brombenzylamide % O% m-1 or p-iodobenzylamide, o
-m+, or p-methylbenzylamide, o-m+, or p-ethylbenzylamide, o-m-1 or p-isopropylbenzylamide, cinnamylamide, aminoethylamide, o-m-1 or p-amino benzylamide, o-m-1 or p-nitrobenzylamide, o+,
m+, or p-methoxybenzylamide, o-m-1 or p-ethoxybenzylamide, o-m-1- or p-
Aminophenethylamide, α-fur7lylamide, a-
Thienylmethylamide, α-pyridylmethylamide, α
-pyridylethylamide, and veridinomethylamide, α
-piperidylmethylamide, morpholinoethylamide,
σ-morpholinylmethylamide, methoxycarbonyl-
(α-mercaptomethyl)methylamide, ethoxycarbonyl-(α-mercaptomethyl)methylamide, and the like.

In addition, as the above-mentioned pharmaceutically acceptable salts, 7 of M.
Examples include acid addition salts at the amino group and base salts at the carboxyl group of the napeptide. Examples of acid addition salts include those with organic or inorganic acids, such as formic acid, acetic acid, propionic acid, trifluoroacetic acid, tartaric acid, hexamaric acid, malic acid, maleic acid,
Salts with carboxylic acids such as oxalic acid and naphthoic acid; salts with sulfonic acids such as methanesulfonic acid, p-toluenesulfonic acid, and naphthalenesulfonic acid; salts with inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, and phosphoric acid; can be given.

Examples of the above-mentioned base salts include salts with inorganic bases, such as alkali metal salts, alkaline earth metal salts, ammonium salts, and salts with organic bases, such as amines. salt, sodium salt,
Examples include potassium salt, calcium salt, ammonium salt, triethylamine salt, ethanolamine salt, tris salt, dicyclohexylamine salt, and the like.

The radiation protection agent according to the present invention is prepared using conventional formulation methods depending on its dosage form. That is, the active ingredients selected from the above-mentioned nonapeptides, their esters or amide derivatives, or their salts are formulated into an appropriate dosage form using pharmaceutically acceptable carriers, excipients, diluents, etc. Prepare. Dosage forms include external use, oral administration,
Various dosage forms suitable for administration routes such as parenteral administration can be provided.

The effects of the radiation protection agent according to the present invention have been confirmed and confirmed by the following experiments. i.e. mouse, rat,
Mammals such as guinea pigs and other animals are irradiated with whole body radiation using an X-ray irradiation device (manufactured by Shimadzu Corporation, Shinai 250I).
After that, the survival rate for 30 days was determined, and at that time, a predetermined amount of the above-mentioned 7-napeptide was administered intraperitoneally, intravenously, or intramuscularly for a predetermined period of time prior to radiation irradiation, or daily or every other day immediately after irradiation. The animals were administered by various routes such as , subcutaneously, and orally, and the weight of the animals was measured to observe whether they were alive or dead. According to the results of this experiment, for example, while all mice in the control group died, the survival rate in the group administered with the drug according to the present invention was 40 to 100%, depending on the irradiation dose.
In addition, in the drug administration group, only in the case of death,
A significant or marked survival benefit was observed compared to the control group. Regarding body weight, weight loss was also significantly suppressed in the drug administration group compared to the control group.

On the other hand, after whole-body irradiation of animals with lethal or sub-lethal doses of radiation, changes in blood cell counts over a certain period of time were measured over time to examine the effect of drugs on promoting recovery from hematopoietic dysfunction. As an indicator; blood cells include red blood cells, reticulocytes,
White blood cells such as lymphocytes and neutrophils, platelets, hemoglobin,
Hematocrit etc. It was found that administration of the drug according to the present invention significantly suppressed the decrease in these blood cells due to radiation irradiation and promoted recovery to the normal range. Furthermore, the immune response of immunocompetent cells in the drug-administered group,
That is, the ability of lung cells to respond to concanavalin A (Con A), and the ability of thymocytes to respond to interleukin-1 (IL-1).
') was orally examined until death in all cases, and was found to be clearly superior to that in the control group. In addition, the ability of immunocompetent cells to produce humoral factors, that is, the ability of peritoneal macrophages (MI) to produce IL-1,
Colony stimulating factor for lung cells, peritoneal M-
stimulating factor.

Similarly, the C3F) production ability was found to be higher in the drug-administered group than in the control group. That is, as is clear from these findings, the drug according to the present invention acts on hematopoietic organs such as bone marrow and lungs, and has the effect of suppressing hematopoietic dysfunction or promoting recovery, and as a result, it has the effect of prolonging the life or saving lives of animals. This is a valuable drug as a preventive and therapeutic agent for radiation damage.

Furthermore, during radiation therapy experiments on tumor-bearing mice, the anticancer effect was enhanced when the drug according to the present invention was administered before or after radiation irradiation, and the anticancer effect was enhanced by administering the drug according to the present invention before or after radiation irradiation. Side effects are reduced, and it becomes possible to effectively increase the dose of radiation that can be used to treat cancer. Furthermore, it is known that radiation irradiation causes cancer in mice, but radiation carcinogenesis in mice is prevented by administering the drug according to the present invention for a certain period of time.

In order to examine the toxicity of the active ingredient in the drug according to the present invention, the active ingredient was administered to mice at 100+B/Jz.
g was subcutaneously administered for 1314 consecutive days, but no abnormalities were observed in appearance. In addition, the active ingredient substance 3
0111 g/hg was administered subcutaneously every day for 21 days, but no abnormalities were observed in appearance, serum biochemistry, or pathological autopsy. As described above, the drug according to the present invention is a safe drug with extremely low toxicity.
It is possible to administer for a long period of time.

Examples of target animals to which the drug according to the present invention can be administered include humans, livestock such as cows, horses, pigs, sheep, goats, herons, dogs, and cats, lions, elephants,
Mammals kept in zoos such as giraffes, bears, gorillas, monkeys, chimpanzees, mice, rats, guinea pigs and other experimental animals, poultry such as chickens,
Pet birds, reptiles, domestic animals, fish, etc. can be cited. The dose was IJ21 for these animals? Usually 0.1Hg to 5001119/day, these are:
For example, the drug may be administered in divided doses once to six times a day, and the dose can be increased or decreased as appropriate depending on the age, medical condition, etc. of the recipient. The route of administration is not particularly limited, but intravenous, intramuscular, subcutaneous, or subcutaneous injections can also be administered.

In addition, by preparing an ointment, it can be applied to the eyes, oral cavity, nasal cavity, skin, etc.;
It can also be administered in the form of eye drops, nasal drops, nasal or oral absorption preparations, aerosols, sprays, oral preparations, etc. To prevent the active ingredient from being rapidly degraded or inactivated in vivo, the active ingredient may be combined with suitable formulation ingredients, such as
It is also possible to formulate a formulation using physiologically harmless solid or liquid materials such as alcoholic, oily or fatty such as lecithin, or suspensions thereof, liposomes, etc., to obtain a formulation that maintains its activity for a long time.

The drug according to the present invention can be used in combination with other drugs, such as biological response modifiers such as immunostimulants.
It can be administered together with glutathione preparations, adenine preparations, cepharanthine preparations, etc., which are said to have a leukopenia recovery effect, and can be added to the preparation to enhance the clinical effect as a combination drug.

The present invention will be explained in more detail by Examples and Experimental Examples below, but the present invention is not limited by these.

Example 1 1 mg of a vial preparation for injection FTS-CH, C00H-2H20 (manufactured by Mitsui Pharmaceutical Industries, Ltd.) was dissolved in distilled water, passed through a sterilized mouth, filled into a vial, and freeze-dried.

Example 2 511 g of an ampoule preparation for injection FTS-CHlCoOH.2H20 (manufactured by Mitsui Pharmaceutical Industries, Ltd.) was dissolved in physiological saline, passed through a sterilized mouth, and filled into an ampoule.

Example 3 2 rng of hypodermic injection FTS-CHlCoOH 2H,O (manufactured by Mitsui Pharmaceutical Industries, Ltd.) per unit dose was suspended in a 2% carboxymethylcellulose PBS (phosphate buffered saline) solution, and soybean phosphatide was added. Lipomal (H
uhtan+aki Oy/Leiras Pharm
aceuticals) or InLralipid (CutLsr La, an intravenous oil-in-water emulsion).
(manufactured by boratories). Lipoma
When using L, FTS dissolved in PBS and Lipom
Al was mixed in equal amounts.

When using Intralipid, FTS-dissolved PB
S solution 2.5ml 12STween 80 (Sigma
Chemicals) 0.1mQ and Intra
Lipid 4.6+x12 was mixed.

Example 4 Liposome preparations There are three types of liposome preparations with different charges, and these are further classified into four types based on their structure.

There are three types of charge: neutral, positive, and negative, and the structure is similar to that of multilamellar liposomes (lJlt/, multilamellar liposomes).
arvesicle), small unilamellar liposomes (S
UV.

small unilamellar vesicle
), and large unilamellar liposomes (LUV, lar
ga unilamellar vesicle), and one with a structure similar to LUV but with several membranes (RE
V, reverse-phase evapora-
Four types of ion vesicles are known.

■ A chloroform solution of FTS-neutral charge liposu-muphosphatidylcholines, phospholipids such as sphingomyelin, and cholesterol is mixed at a molar ratio of 2:1, 4:1, or 1:1, and then mixed. After removing the solvent under reduced pressure, add 1/1 to the amount of lipid.
00-1/1000 equivalent of FTS in PBS (phosphate buffered saline) was added and Vortex m1xe
After thorough mixing at r, MLV was obtained.

Furthermore, SUv was obtained by ultrasonication at a temperature above the phase transition temperature (Tc) of phospholipids.

Add calcium chloride aqueous solution to the obtained SUV and heat at 37°C.
After incubating for 1 hour with EDTA
and incubate for 30 minutes at 37°C to
When + was removed, LUV was obtained.

The method for preparing 12El/ is as follows. That is, after removing the solvent from a chloroform solution of lipids under reduced pressure, an appropriate amount of diethyl ether was added to the solution, which was thoroughly dissolved.
A PBS solution of S was added and subjected to ultrasonic treatment, resulting in a homogeneous single-phase solution. After concentrating the obtained solution under reduced pressure at room temperature, a PBS solution was added and thoroughly mixed using a Vortex n+1xer to obtain REV.

(2) FTS-encapsulated positively charged liposomes The preparation method is the same as that for the above-mentioned neutrally charged liposomes, except that the constituent components of the lipids are different.

Phosphatidylcholines, phospholipids such as sphingomyelin, cholesterol, and positively charged higher aliphatic amines such as stearylamine in a molar ratio of 7:2:l or 4.
:l:1 to obtain a lipid component, and FT in the same manner.
S was enclosed.

■ FTS Negatively Charged Lipos-Mufos 7 Phospholipids such as atidylcholines and sphingomyelin, cholesterol and negatively charged higher aliphatic esters such as dicetyl phosphate and sulfatide in a molar ratio of 7:2:1 or 4. :l:l to obtain a lipid component, and FTS was encapsulated in the same manner.

Example 5 Ointment FTS-CH, C0OH·2u*o (manufactured by Mitsui Pharmaceutical Industries, Ltd.) 21IIg was dissolved in purified water. Next, white petrolatum 2
5g, stearyl alcohol 20g, HCO-604g
Take 1 g of glyceryl monostearate, mix and add 12 g of propylene glycol, 0.1 g of methyl hydroxybenzoate, and 0 sludge of propyl hydroxybenzoate (containing FTS) and mix thoroughly to form an emulsion. After that, the mixture was prepared by continuing the mixing operation until it was cooled and solidified.

Example 6 Suppository FTS-CH3COOH-2H! 0 (manufactured by Mitsui Pharmaceutical Industries, Ltd.) lo + mg was dispersed in pre-warmed hard fat,
The total amount was 2g.

Implementation #7 Nasal capsules FTS O, 05+xf under sterile conditions for 29.95 minutes 9
Migdiol 812 neutral oil (manufactured by Dynamite Nobel). The solution was filled into conventional unit dose dispensers, which were loaded into drive capsules prior to use.

Example 8 Nasal Drop The following amounts of sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium chloride, and EDTA-disodium salt were dissolved in distilled water at room temperature. FTS was dissolved in this solution and filtered through a membrane filter.

F T S , 0.10u Sodium Hydrogen Phosphate・2HiO0-30119 Sodium Dihydrogen Phosphate・12Hx0 10. lhg Benzalkonium chloride 9.10mg Ethylenediaminetetraacetic acid-disodium salt (EDTA) 0.50
mg Sodium chloride 4゜50mg
Distilled water 987.
60mg pH value 5.
0±0.3 Example 9 Nasal spray preparation FTS-CH3COOH・2 u x o (manufactured by Mitsui Pharmaceutical Industries, Ltd.) 2119 was suspended in hydroxypropyl cellulose or hydroxypropyl methyl cellulose and mixed with a spray preparation using a spray preparation machine. did.

Examples of pharmacological experiments and toxicity experiments regarding the drug of the present invention are listed below.

Experimental Example 1800 Effect on Roentgen (R) Irradiated Mice A group of 10 to 15 male IO-week-old C3H/He mice were prepared.

The whole body of the mouse was irradiated for 8 minutes using an X-ray irradiation device (Shiai 250I [manufactured by Shimadzu Corporation]).

FTS-CH・, C0OH・2H80 used in Example 1
was subcutaneously administered to mice at 100 μg ↓ times a day.
It was administered continuously for 4 days. In the pre-administration group, administration was started 2 days before irradiation. For the post-administration group, the first administration was performed immediately after irradiation. As control groups, we prepared a group in which bisibanil 1KE was subcutaneously administered only once immediately after irradiation, and a group in which physiological saline was administered daily. The results are shown in Table 1. As is clear from Table 1, the drug according to the present invention was shown to clearly prevent or inhibit death of mice due to radiation irradiation,
Its value as a preventive and therapeutic agent for radiation damage has been demonstrated. In particular, the effect was more pronounced in the pre-administration group.

Experimental Example 2 Effect on 90OR irradiated mice After 9 minutes of X-ray irradiation in the same manner as in Example 1, 0, ], 2.3.4.
5.7.8.9.10S11% Total of 12 times on the 12th day, 1
Once a day, lOOu y=FTS-CHsCOOH・
2H30 was administered subcutaneously to mice. The results are shown in Table 2.

The FTS-administered group had prolonged survival despite exposure to a high radiation dose of 900R.

Experimental example 3 Effect example 1 on 600R irradiated mice,
The mice were irradiated with X-rays for 6 minutes in the same manner as in 2. From 2 days before irradiation, drug and shite, FTS-CH for 14 consecutive days.
, C00H-2H,O was subcutaneously administered in an IEI dose of 100 μl once. Although the X-ray irradiation was less than a lethal dose, 19
Days later, in the control group, out of 10 animals survived, and more than half of them died, whereas in the drug-administered group, 0 out of 10 animals survived. The results are shown in Table 3.

Experimental Example 4 Blood Test In addition to the irradiation of the mice for life and death observation conducted in Experimental Example 3, 60
0R X-ray irradiation was performed. Furthermore, another group of mice was prepared, and this group was subjected to 400R X-ray irradiation.

The 600 R irradiation group and the 400 R irradiation group were each divided into two groups, a group pre-administered with 100 μl of the drug and a control group. Blood was collected orally from each mouse, and
White blood cell count (WBC), red blood cell count (RBC), reticulocyte count (RET), platelet count (PLT), hemoglobin count (HGB), hematocrit value (HCT)
was measured.

Representative examples are shown in Table 4. It was observed that each blood parameter of the X-ray irradiated mice was clearly improved by drug administration compared to the control group.

Experimental Example 5 Weight Measurement The weight of the mice in each experimental group of Experimental Example 3 was measured every day, and changes in body weight were observed. The results are shown in Table 5, and it was found that the drug-administered group clearly weighed more than the control group.

Experimental Example 6 Toxicity test 5 mice of the active ingredient were administered to 1 group of 5 male mice of the ddY strain, 5 weeks old.
011g/kg and 100mg/kg each daily
Although the drug was administered subcutaneously for 4 days, no toxicity was observed.

Experimental Example 7 Toxicity Test 30 yxy/bg of the active ingredient was subcutaneously administered to 1 group of 5-week-old Wistar rats for 2113 consecutive days.
No toxicity was observed.

As mentioned above, in the medical field for protecting against radiation damage, where there are almost no effective drugs other than the few agents used to restore white blood cell count, the drug according to the present invention is useful for protecting the immune system or living body. It is revolutionary in that it has excellent preventive and therapeutic effects on radiation damage by activating the defense system. In addition, since nonabegtide (FTS) used in the present invention is an animal-derived peptide and a natural substance, FTS with a similar amino acid sequence
Unlike S analogues (analobes), they are completely non-toxic to living organisms, and there are no problems such as antigenicity or anaphylactic shock. Therefore, the drug according to the present invention can be used as a safe and useful medicine for humans and animals.

Claims (1)

[Claims] Contains as an active ingredient a Noah peptide having the following amino acid sequence [there is a gene sequence], or an ester, amide, or a pharmaceutically acceptable salt thereof at the carboxyl group of asparagine at its C-terminus. A radiation damage protective agent characterized by: