JP2001163799A - Low antigenic humectant, low antigenic external preparation and low antigenic beverage - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a low antigenic humectant, a low antigenic external preparation and a low antigenic beverage not inducing an anaphylactic reaction, having a high moisture retaining effect. SOLUTION: This low antigenic humectant comprises >=50 wt.% of a peptide composition having <=20,000 molecular weight and an amino acid sequence of (Gly-X-Y)n obtained by specifically decomposing a gelatin component or a collagen component with a collagenase enzyme. A low antigenic external preparation of cosmetic, or the like, contains >=0.005 wt.% of the low antigenic humectant.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a low-antigenic humectant, a low-antigenic external preparation and a low-antigen preparation which do not induce an anaphylactic reaction and which are obtained by specifically decomposing a gelatin component or a collagen component using a collagenase enzyme. Drink.

[0002]

2. Description of the Related Art Various cosmetics and quasi-drugs such as basic cosmetics, makeup cosmetics, hair cosmetics, body cosmetics and the like have been developed to keep the human body clean or to dress beautifully. As a humectant or a stabilizer for a system, collagen or gelatin or a decomposition product obtained by treating them with an acid or heat is used. Many amino acids that make up collagen molecules have hydrophilic side chains, and because they can absorb a lot of water molecules, they have a high moisturizing effect, are familiar with the skin, and are less likely to cause allergic reactions. Based on widely used.

[0003]

On the other hand, the number of patients with allergic diseases, which are said to be civilized diseases, has recently been increasing in countries in Europe and the United States.
Even in Japan, the number is increasing rapidly, and it is said that even one in three people has some kind of allergic disease. Against the background of such an increase in the number of allergic patients, patients who have side effects such as anaphylaxis to gelatin and collagen, which were considered to have little antigenicity / allergenicity (having gelatin-specific IgE antibodies), Recently, it is gradually increasing, and it is starting to become a social problem. In fact, scholarly presentations on these have only been scattered since the 1990s (Kelso, JM et al., J. Al.
lergy Clin. Immunol., 91, 867-872, Sakaguchi,
M. et al., Infection / Inflammation / Immunity, Vol. 26, pages 48-50).

[0004] In addition to collagen and gelatin, those commonly used as humectants include polyhydric alcohols such as glycerin and propylene glycol, urea, lanolin, hyaluronic acid, vitamin E and the like. Recently, ceramides have also attracted attention, but polyhydric alcohols have discomfort such as stickiness, urea has been reported to be irritating due to high osmotic pressure, and lanolin has been reported to have side effects such as contact dermatitis. I have.

In recent years, dry skin, sensitive skin, rough skin, atopic dermatitis and the like have been increasing due to external factors such as drying, ultraviolet rays, and stress, and internal factors such as aging of the skin due to aging. Because it is closely related to skin moisturizing, the development of a safer moisturizer has been required.

In view of the above circumstances, the present inventors have conducted intensive studies on gelatin or collagen derivatives that do not exhibit antigenicity or allergenicity.
As a result, the collagenase enzyme alone or immobilized on various carriers is directly acted on the raw material containing the gelatin component or the collagen component, and the specific enzymatic degradation is carried out. It has been found that a peptide composition having a molecular weight range of 1,000 or less and retaining (Gly-XY) _n , which is a characteristic amino acid sequence of the above, can be obtained in high yield (JP-A-7-82299).

Furthermore, the present inventors have conducted intensive studies and as a result, by adding some ingenuity to the above-mentioned production process, not only peptides having a molecular weight of 1,000 or less but also substantially no antigenicity / allergenicity are exhibited. , Molecular weight about 1,000-20,000
It has been found that peptide compositions in the range of can be prepared. This low antigenic peptide composition has an effect of stabilizing various physiologically active substances and biologically active substances, similarly to conventional gelatin, collagen and their decomposed products (JP-A-9-176196, JP-A-11-176196). No. -12196), especially as a vaccine stabilizer.

However, conventionally, it has been considered that the moisturizing effect of collagen and gelatin becomes weaker as the molecular weight is reduced.
No use of a peptide composition having a molecular weight of 20,000 or less shown in JP-A-9-176196 and JP-A-11-12196 as a humectant was considered.

SUMMARY OF THE INVENTION The present invention has been made to solve the above problems, and it is a low antigenic humectant, a low antigenic external preparation and a low antigen which do not induce an anaphylactic reaction and have a high moisturizing effect. The purpose is to provide a sexual beverage.

[0010]

Means for Solving the Problems The present inventors have proposed a peptide composition obtained by specifically decomposing a gelatin component or a collagen component using a collagenase enzyme, even if it has a molecular weight of 20,000 or less. It has been found that not only does it not substantially exhibit the property / allergenicity, but also has a high moisturizing effect.

Therefore, the low antigenic humectant according to the present invention comprises:
A gelatin component or a collagen component is specifically decomposed with a collagenase enzyme and has a molecular weight of 20,0.
It is characterized by containing a peptide composition having an amino acid sequence of (Gly-XY) _n of not more than 50% by weight of 50% by weight or less. In the formula of (Gly-XY) _{n in} the amino acid sequence, X and Y are any amino acid residues other than Gly, for example, P
ro or Hyp, and n is a natural number.

The low antigenic humectant according to the present invention may contain at least 50% by weight of a liposome of the peptide composition. Moreover, the low antigenic humectant according to the present invention may contain 50% by weight or more of a microencapsulated version of the peptide composition. In the low antigenic humectant according to the present invention, it is preferable that the peptide composition contains n = 1, 2, or 3 in an amount of 5% by weight or more.

The low-antigenic external preparation according to the present invention is characterized by containing 0.005% by weight or more of the low-antigenic humectant. The low-antigenic external preparation according to the present invention may be an external preparation for atopic dermatitis, a dry skin (xerosis), a baby, a sensitive skin, or a skin care for nursing care or a cosmetic. And eye drops for dry eyes. The external preparation with low antigenicity according to the present invention may be a quasi-drug.
Cosmetics include cleansing cosmetics, hair cosmetics, basic cosmetics, make-up cosmetics, aromatic cosmetics, tanning / sunscreen cosmetics, nail cosmetics, eyeliner cosmetics, lip cosmetics, oral cosmetics, bath cosmetics, and the like. Specific examples include lotions, emulsions, serums, packs, foundations, lipsticks, soaps, hand creams, shampoos, rinses, treatments, and the like. Examples of quasi-drugs include medicated cosmetics, hair restorers, and the like, in addition to eye drops for dry eyes.

The low antigenic humectant according to the present invention is non-sticky, has good spreadability, has high skin permeability, and improves the moisturizing power of the skin. The external preparation with low antigenicity according to the present invention is useful for improving the moisturizing power of skin or eyes with reduced moisturizing power.

[0015] The low antigenic beverage according to the present invention is characterized by containing the low antigenic humectant in an amount of 0.005% by weight or more. Examples of the low antigenic beverage include an energy drink. The low antigenic beverage according to the present invention improves the moisturizing power of the mouth and throat and moisturizes it effectively.

The gelatin or collagen component, which is the starting material of the low-antigenic humectant according to the present invention, comprises cow, pig,
Fish bones such as bones, skins, tendons, and sharks of animals such as birds and whales can be prepared as raw materials. Collagenase enzymes include Clostridium histolyticum, Streptomyces parvulu
An enzyme that specifically cleaves the amino side of glycine of (Gly-XY) _n , which is derived from bacteria such as s, actinomycetes or fungi, is used. In addition, these enzyme genes are genetically engineered into specific vectors and produced by other cells or animals such as lactic acid bacteria and yeast, and are recombinantly produced enzymes that have similar substrate specificity. Enzymes may be used.

A particular point to note when using the collagenase enzyme in the present invention is the purity of the collagenase enzyme. Normally, collagenase enzymes prepared from various cells may be contaminated with other proteases (proteases). If a large amount of this impure enzyme is contained, proteins other than the gelatin component or collagen component in the raw material will be degraded, and the gelatin or collagen component itself will be non-specifically decomposed by the impure enzyme, so that it will be purified. The quality of the peptide composition is reduced. Consequently, it is likely to cause anaphylaxis. Therefore, it is necessary to pay close attention to the purity of the collagenase enzyme used, together with its substrate specificity.

The collagenase enzyme may be used in a free form, or may be used as an immobilized enzyme in which the collagenase enzyme is bound to various carriers by a physical adsorption method or a chemical bonding method. As a method for enzymatic degradation with a collagenase enzyme, (a) a batch method, (b) a column method, or (c) a method combining these can be used.

The production lines according to the methods (a) to (c) and the form of the collagenase enzyme to be used can be freely combined. The production of the low-antigenic humectant according to the present invention can be carried out according to the method described in JP-A-7-82299, but other methods are also possible. Rather, it is preferable to select a method according to the gelatin component or collagen component as a raw material, or to select a method suitable for maintaining the specificity and purity of the collagenase enzyme.

More specifically, one example of the method for producing the low antigenic humectant according to the present invention is to use gelatin or collagen as a starting material and improve the enzyme recovery as shown in the following Examples. And a bioreactor method using a batch method or a column method using an immobilized collagenase enzyme. That is, the collagenase enzyme is bound to various carriers, for example, chitopearl or the like, by a physical adsorption method or a chemical bonding method, and the gelatin solution or the decomposition solubilized at a constant temperature in a normal system packed in a column for chromatography is used. Enzymatic degradation is carried out through denatured collagen at a temperature that does not occur, preferably at 40-45 ° C. At this time, the rate of feeding the collagen raw material is appropriately selected depending on the activity of the immobilized enzyme and the required degree of decomposition.

Hereinafter, the present invention will be described in detail with reference to examples. However, these examples do not limit the scope of the present invention. Further, the method of using the peptide composition derived from gelatin or collagen as a humectant according to the present invention can be carried out according to an already known operation method.

[0022]

[Example 1] High purity gelatin (Miyagi Chemical Industry Co., Ltd.) 50
g in 1,000 ml of 20 mM Tris-HCl buffer (pH 7.4) /0.1
After dissolving in M NaCl while heating, the mixture was cooled to 50 ° C. The immobilized enzyme for enzymatic degradation was 100 mg of collagenase enzyme (a high-purity product purified from type IV, manufactured by Washington, Inc.).
It was prepared by binding to 50 g of chitopearl (manufactured by Fuji Boseki) using a two-crosslinking reagent. The amount of binding to the carrier before and after binding
It was calculated by measuring the change in absorbance at 280 nm.
The binding rate was 99% or more. At the time of use, this immobilized enzyme is filled into a double column type bioreactor with a pH sensor installed between columns, and 20 mM Tris-HCl
Washing and equilibration were carried out well with a buffer (pH 7.4) /0.1 M NaCl buffer. In the pH measurement system, the pH sensor installed between the two columns detects the change,
The system is such that concentrated Tris buffer flows in from the connecting tube.

The high-purity collagen obtained in the above steps is
The column was applied to the column of the double collagenase enzyme immobilization prepared in the above step, and the enzyme was decomposed by the column method. During this time, the flow rate was controlled at 50-80 ml / min, and the column temperature was controlled at 39 ± 1 ° C. Final (2
The end of the enzyme reaction from the column
Filtration was performed with a 0.45 μm filter.

The filtrate is spray-dried (spray dryer)
And then gel filtration using a gel filter (trade name: Superdex 30pg, manufactured by Pharmacia) or reverse phase chromatography using an ODS column (manufactured by YMC) to obtain a molecular weight of 1,000 or less. Alternatively, a peptide composition having a molecular weight of about 20,000 or less was purified. These peptide compositions were prepared in Example 1
Is a low antigenic humectant.

The molecular weight distribution of each peptide composition obtained in the above process was determined by high performance liquid chromatography: HPLC (LC-10A, manufactured by Shimadzu Corporation, column: Superdex peptide).
Was measured. Each sample was filtered through a 0.2 μm membrane filter before injection into the HPLC column. For each peptide composition obtained from Example 1, that is, the peptide fraction having a molecular weight of about 20,000 or less and the peptide fraction having a molecular weight of 1,000 or less, the average molecular weight,
Table 1 shows the ratio of peptides having a molecular weight range of 500 or less.
Summarized in

[0026]

[Table 1]

Each of the peptide compositions obtained in the above steps, that is, a peptide composition having a molecular weight of about 20,000 or less and a peptide composition having a molecular weight of 1,000 or less are lyophilized and then lyophilized from the NH ₂ -terminal amino acid and NH ₂ terminus. The second amino acid was tested by Edman degradation. As a result, it was found that 95.7% and 97.5% of the amino acids at the NH ₂ terminus of both were glycine, respectively, and retained the (Gly-XY) _n structure which is a characteristic amino acid sequence of collagen according to the present invention. Prove that you have. Each peptide composition obtained in the above step can be used as a low antigenic humectant.

An assay method for the disappearance of the antigenicity / allergenicity of the peptide composition (low antigenic humectant) obtained in the above step and the results thereof will be described.

[Preparation of Gelatin Antiserum (IgG Type)] Gelatin derived from cow skin and pig skin was dissolved in PBS to 2 mg / ml, and a solution obtained by filtering through a 0.22 μm filter was used in the same amount as Freund's complete adjuvant. The emulsion was prepared by mixing, and 1 ml was injected into three rabbits. Three weeks later, a solution of the same peptide composition was mixed with an equal volume of incomplete Freund's adjuvant to form an emulsion, which was also injected into rabbits. This operation was repeated three times, and an antiserum was obtained one week after the final immunization.

[Preparation of Gelatin Antiserum (IgE Type)] A solution obtained by dissolving gelatin derived from cow skin and pig skin to 2 mg / ml in PBS and sterilizing by filtration with a 0.22 μm filter was subjected to aluminum hydroxide (Alum). To precipitate,
It was adjusted to 100 μg / ml after washing, and 1 ml was injected into the skin of three guinea pigs. Four weeks later, 3 to 5 days after the booster was performed in the same manner, antiserum was obtained.

[Preparation of Gelatin-Sensitized Immunoballs] Gelatin derived from cowskin or pigskin is immobilized on the functional group (NH ₂ group) of an aminated polystyrene ball (manufactured by Sumitomo Bakelite Co., Ltd.) activated with a crosslinking reagent. A gelatin-sensitized immunoball was prepared by performing a blocking operation using bovine serum albumin or a surfactant.

[0032]

[Test 1] [Enzyme immunoassay (antigenicity test-1)] (Assay of antigenicity by inhibition reaction) Into a gelatin-sensitized immunoball, (1) the peptide composition having a molecular weight of about 20,000 or less obtained in Example 1 Product (low antigenic humectant of Example 1),
(2) a peptide having a molecular weight of 1,000 or less obtained in Example 1 (low antigenic humectant of Example 1), (3) a partially degraded gelatin having a molecular weight of 200 to 7,000 obtained by thermal decomposition (comparative example), (4) 200 μl of each of enzymatically decomposed gelatin having a molecular weight of 500 to 12,000 (comparative example) and (5) gelatin (comparative example), which were enzymatically decomposed with trypsin and pepsin, were added.
Then, 200 μl of either the above-mentioned IgG type rabbit gelatin antiserum or IgE type guinea pig gelatin antiserum was added thereto and reacted at 37 ° C. for 30 minutes to obtain (1) to (5) in the reaction system between the antiserum and the gelatin antigen. ) Competition reaction of each component was performed.

Then, the cells were washed, and a horseradish peroxidase (HRP) -labeled complex of a goat anti-rabbit IgG antibody (Cosmo Bio) or a horseradish peroxidase (HRP) -labeled complex of a goat anti-guinea pig IgE antibody (Cosmo Bio). ) Was subjected to a secondary reaction. After reacting at 37 ° C. for 1 hour, the activity of the HRP-labeled complex remaining bound to the immunoball is measured to determine (1) to (5) the antigenicity and allergenicity of each component and the degree of the competitive reaction. Considered from. Table 2 shows the results. From the results in Table 2,
The low-antigenic humectant of Example 1 of (1) and (2) has an inhibition rate of 0%, whereas the comparative examples of (3) to (5) have antigenicity, whereas It can be seen that it does not have

[0034]

[Table 2]

[0035]

[Test 2] [Passive Cutan anaphylaxis
eous Anapylaxis: PCA) (antigenicity test 2)] Using sterile physiological saline, guinea pig anti-bovine gelatin antiserum 1/2 dilution series (1/10, 1/20, 1/40, 1/80, 1 / 160) were prepared, and 50 μl of each of the diluted sera was injected into the back skin of two SD rats (male, 8 weeks old) (4 in total) whose hairs were shaved. Twenty-four hours later, one of them received 1.0 ml of a 0.6% Evans blue solution containing 1 mg of the peptide composition having a molecular weight of about 20,000 or less obtained in Example 1 (the low-antigenic humectant of Example 1). It was injected via the tail vein. As a positive control for the peptide composition, a second SD
Rats were similarly injected with 1.0 ml of a 0.6% Evans blue solution containing 1 mg of bovine gelatin via the tail vein. 60
After 4 minutes, all 4 animals were sacrificed, the back skin was peeled off, and purple spots were observed.
Their size was measured.

Judgment was made when the purple spot diameter was 10 mm or more (++).
Or (+++), 9 mm to 5 mm to (+), 4 mm to 1
mm was (±), and the case where no purpura was generated was (-). Table 3 shows the results. From the results in Table 3, it can be seen that, in the case of bovine gelatin, purpura occurs even in a dilution series of 1/160, whereas in the case of the peptide composition having a molecular weight of about 20,000 or less (low antigenic humectant) obtained in Example 1, Shows that purpura does not occur even in a 1/10 dilution series, indicating no antigenicity.

[0037]

[Table 3]

[0038]

[Test 3] [Fluorescent enzyme immunoassay (antigenicity test 3)] (Assay of allergenicity by inhibition reaction) From 6 patients exhibiting allergic symptoms to gelatin (patients A to F in Table 4) When performing a fluorescent enzyme immunoassay for measuring a gelatin-specific IgE antibody using the collected blood serum and the above-mentioned gelatin-sensitized immunoball, the specific IgE antibody of a patient who was positive by the fluorescent enzyme immunoassay was determined. The extent to which the titer was inhibited by the peptide composition of Example 1 (low antigenic humectant) was determined by measuring the fluorescence intensity of the fluorescent substrate degraded by the labeling enzyme. As a second antibody for detecting a gelatin-specific IgE antibody, a mouse anti-human IgE antibody labeled with β-galactosidase was used, and the enzyme activity was assayed using a fluorescent substrate.

As a result, as shown in Table 4, peptides having a molecular weight of about 20,000 or less and peptides having a molecular weight of 1,000 or less obtained in Example 1 (low antigenic humectant of Example 1)
No decrease in the antibody titer (fluorescence intensity) due to the inhibition reaction was observed for both components, and it was found that they had no reactivity with the gelatin-specific IgE antibody. On the other hand, the original raw material gelatin, heat-decomposed gelatin or gelatin decomposed by non-specific protease causes strong inhibition,
It was shown to react well with gelatin-specific IgE antibodies, revealing part of the cause of anaphylaxis.
By performing this test 3, it is possible to know whether the peptide composition (low antigenic humectant) has reactivity with gelatin-specific IgE that induces type I allergy.

[0040]

[Table 4]

[0041]

[Test 4] [Percutaneous absorption test (investigation by microautoradiography)] 10 mg of a peptide composition (low-antigenic humectant) having a molecular weight of about 20,000 or less according to Example 1 labeled with ³ H was precisely weighed. Propylene glycol,
A transdermal preparation was prepared by adding 1.49 g of purified water and 0.2 g of ethanol to 0.3 g of a liquid obtained by mixing glycerin and PEG 1500 at a weight ratio of 6: 4: 5. The preparation for transdermal administration was applied with a spatula to the rat on the previous day, which was shaved under ether anesthesia, while dropping a small amount at the center of the back.
A microautoradiogram was prepared using the excised skin, and the distribution of radioactivity in the skin was examined.It was observed throughout the stratum corneum, granular layer, spinous layer, and basal layer, and even to the dermis. A state of reaching was observed. This confirmed that the peptide composition (low antigenic humectant) of Example 1 had high transdermal absorbability.

[0042]

[Formulation Example 1] [Lotion] A molecular weight of about 20,000 according to Example 1.
After dissolving 0.77 g of the following peptide composition (low antigenic humectant) and 7.7 g of PEG 1500 in 50 ml of purified water, 9.24 g of propylene glycol and 6.16 g of glycerin were added and mixed well. A solution obtained by dissolving 0.154 g of paraben in 15.4 ml of ethanol was added thereto, and purified water was added to make a total amount of 154 ml, and the mixture was further mixed well. As a result, a low-antigenic lotion having high moisturizing properties and good spreadability at the time of use and not sticky was obtained.

[0043]

[Formulation Example 2] [Emulsion] propylene glycol 5.0 g,
3.0 g of PEG and 1.0 g of triethanolamine were added to 60 ml of purified water, and the temperature was adjusted to 70 ° C. to prepare an aqueous phase. 2.0 g of stearic acid, 1.0 of cetyl alcohol
g, petrolatum 2.0 g, squalane 5.0 g, and glycerol tri-2-ethylhexanoate 2.0 g.
The mixture was dissolved at 5 ° C, and 2.0 g of sorbitan monooleate and 0.1 g of paraben were added thereto, and the mixture was adjusted to 70 ° C. This oil phase was added to the previously prepared aqueous phase, and further, a peptide composition (low antigenic humectant) obtained by liposomeizing the peptide composition having a molecular weight of about 20,000 or less according to Example 1 (0.
After adding 15 ml of 2 g phospholipid / ml) and stirring and mixing well, the emulsified particles were homogenized with a homomixer, followed by degassing, filtration and cooling. As a result, a low-antigenic emulsion having a high moisturizing property and a good stickiness at the time of use was obtained.

[0044]

[Formulation Example 3] [Moisturizing serum] Molecular weight of about 2 according to Example 1
5.0 or less peptide composition (low antigenic humectant) 5.0
g, sorbitol 8.0 g, propylene glycol 5.
0 g and 7.0 g of PEG 1500 in 66.7 ml of purified water
Was dissolved. 1.0 g of POE oleyl alcohol ether, 0.2 g of olive oil, and 0.1 g of paraben were dissolved in 7.0 g of ethanol, and the aqueous phase of Formulation Example 2 was added and dissolved. As a result, a low-antigenic moisturizing essence having high moisturizing properties and good spreadability when used was obtained.

[0045]

Formulation Example 4 [Hand cream] Peptide composition having a molecular weight of about 20,000 or less (low antigenic humectant) according to Example 1
5 g, glycerin 15.0 g, propylene glycol 3.0 g, and potassium hydroxide 0.2 g were purified water 66.2.
The mixture was heated and adjusted to 70 ° C. and the aqueous phase was prepared. 3.0 g of stearic acid, 3.0 g of stearic acid monoglyceride
g, 3.0 g of petrolatum, 6.0 g of liquid paraffin, and 0.1 g of paraben, and the mixture was adjusted to 70 ° C. The oil phase was added to the previously prepared aqueous phase, and the mixture was thoroughly stirred and mixed. The homogenized particles were homogenized with a homomixer, followed by degassing, filtration, and cooling. As a result, a low-antigenic hand cream with high moisturizing properties and good spreadability at the time of use was obtained.

[0046]

[Formulation Example 5] [Lotion for dry skin] 2.0 g of the peptide composition (low antigenic humectant) having a molecular weight of about 20,000 or less according to Example 1 was dissolved in 50 ml of purified water, and 0.1 g of paraben was added to ethanol. One dissolved in 10.0 ml was added. Further, add purified water to make the total amount 100 ml.
And mixed well. As a result, a low-antigenic dry skin lotion for dry skin was obtained, which had high moisturizing properties and had good spreadability when used.

[0047]

[Formulation Example 6] [Ophthalmic solution for dry eye] Peptide composition having a molecular weight of about 20,000 or less according to Example 1 (low antigenic humectant)
0.5 g was dissolved in 50 ml of purified water, and a solution obtained by dissolving 0.02 g of paraben in 2.0 ml of ethanol was added thereto. Further, add purified water to make the total amount 100 ml.
And mixed well. As a result, a low-antigenic dry eye drop having high moisturizing power was obtained.

[0048]

According to the low-antigenic humectant, low-antigenic external preparation and low-antigenic beverage of the present invention, not only they do not show antigenicity / allergenicity, but also feeling of use, permeability to skin and moisturizing. Excellent in nature.

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Claims (9)

[Claims] The present invention relates to a method for producing a protein comprising the steps of: (1) a gelatin component or a collagen component obtained by specifically decomposing a gelatin component or a collagen component using a collagenase enzyme;
Y) A low-antigenic humectant comprising 50% by weight or more of the peptide composition of _n . 2. The method according to claim 2, wherein the gelatin component or the collagen component is specifically decomposed using a collagenase enzyme, and has a molecular weight of 20,000 or less and an amino acid sequence of (Gly-X-
Y) 50 liposomes of _n peptide composition
A low-antigenic humectant, characterized in that the humectant is contained in an amount of at least% by weight. 3. The method according to claim 1, wherein the gelatin component or the collagen component is specifically decomposed using a collagenase enzyme, and has a molecular weight of 20,000 or less and an amino acid sequence of (Gly-X-
Y) A low-antigenic humectant comprising at least 50% by weight of microencapsulated _n- peptide composition. 4. The peptide composition according to claim 1, wherein n = 1, 2, or 3.
4. The low antigenic humectant according to claim 1, wherein the humectant is contained in an amount of 5% by weight or more. 5. An external preparation with low antigenicity, comprising 0.005% by weight or more of the low antigenic humectant according to claim 1, 2, 3, or 4. 6. The low antigenic external preparation according to claim 5, which is an external preparation for skin care for atopic dermatitis, dry skin, baby, sensitive skin or nursing care. 7. The low antigenic external preparation according to claim 5, which is a cosmetic. 8. The low antigenic external preparation according to claim 5, which is an eye drop for dry eye. 9. A low-antigenic beverage comprising 0.005% by weight or more of the low-antigenic humectant according to claim 1, 2, 3, or 4.