JP2010105933A - Hair-nourishing cosmetic - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a hair-nourishing cosmetic exhibiting hair-nourishing effects by the absorption from the scalp by being coated on the head part, improving finger combability and tensive and stiff feeling of the hair, and optionally exhibiting the effects for reducing squeaky feeling and dry feeling of the hair. <P>SOLUTION: The hair-nourishing cosmetic exhibiting the excellent finger combability, and reducing the squeaky feeling contains two kinds of silk hydrolyzates (a fibroin-originated silk hydrolyzate and a sericin-originated silk hydrolyzate) in a specific formulated ratio. The excellent hair-nourishing effects and the tensive and stiff feelings can be imparted by coating and using the nourishing cosmetic containing Porphyra yezoensis or a hydrolyzate thereof on the head part. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a hair nourishing cosmetic that exhibits a hair-growth effect by being absorbed from the scalp, and at the same time adheres to the hair, thereby improving the feeling of fingering and the feeling of elasticity.

  Along with changes in the social environment and an increase in the number of elderly people, an increasing number of people suffer from thinning and hair loss. Thinning and hair loss are generally said to have a large genetic factor. Causes include "imbalance of male and female hormone balance", "insufficient daily scalp care", "excessive stress", "rapid diet", "biased diet" Yes. Also, regardless of gender, an increasing number of people are worried about “decrease in elasticity” and “occurrence of softness” of hair due to aging.

  Hair grows as hair matrix cells repeat division and keratinize. In order for hair matrix cells to divide normally, it is necessary to absorb nutrients from the surrounding capillaries. However, due to aging and changes in the social environment as described above, when the capillaries of the scalp become thinner and the blood flow decreases, sufficient nutrients do not reach the hair matrix cells, resulting in `` thin hair '' , Phenomena such as a reduction in the “harshness” of hair occur. Therefore, in general, hair growth agents, hair nourishing agents, hair growth agents (hereinafter sometimes collectively referred to as “hair restoration cosmetics”) are components having a “cell activation effect” or “blood circulation promotion effect”. It contains a certain component and has a function of promoting hair matrix cell division.

  In addition, in order for hair to grow healthy, it is necessary to keep the scalp (pores) environment clean. For hair nourishing cosmetics, ingredients with “bactericidal and bacteriostatic effects” and “anti-inflammatory effects” Certain ingredients are also blended. Thus, hair nourishing cosmetics generally contain active ingredients such as “cell activation”, “blood circulation promotion”, “bactericidal and bacteriostatic”, “anti-inflammatory” as active ingredients. .

  People who suffer from “thinning”, “hair loss”, and a decrease in “harshness” of hair strongly desire to increase the amount of hair and impart “harshness”. Various hair growth agents, hair nourishing agents, and hair growth agents have been developed (for example, Non-Patent Documents 1 to 4).

  By the way, Susabinori and its degradation product (hydrolyzate) are mainly used in foods, and it is known that oral administration causes blood pressure lowering action and the like. For example, Patent Document 1 discloses that a polysaccharide-degrading enzyme produced by a microorganism belonging to the genus Vibrio is allowed to act on seaweeds belonging to the red alga Amori genus, so that Susavinori is obtained as a degradation product of seaweeds, and this degradation product is added. An edible composition is disclosed.

  Patent Document 2 also proposes a method for decomposing Susabiori. In this method, it has been proposed that pepsin is decomposed at around 50 ° C. for 12 hours or longer. The resulting degradation product (peptide mixture) has angiotensin converting enzyme inhibitory activity and has a specific amino acid sequence. It has been shown. It has been confirmed that the decomposed product of Susavinoly obtained in this way also has a blood pressure lowering action, a plasma cholesterol lowering action and the like by oral administration. However, there is no example in which Susabinori and its decomposition products are used for hair growth agents, hair growth agents, and hair nourishing cosmetics, and their effects are not known.

  Meanwhile, hair nourishing cosmetics generally contain alcohol in order to dissolve active ingredients. However, when alcohol adheres to the hair, the touch is deteriorated, a feeling of tingling or a feeling of roughness is generated, and the condition of the hair is deteriorated. Such a phenomenon often becomes a problem, and in hair nourishing cosmetics, it is also an important requirement to have an effect of suppressing a feeling of squeaky or rustling.

Various types of hair nourishing cosmetics that have an effect of suppressing a feeling of squeakiness or a soft feeling have been proposed so far. For example, Patent Document 3 discloses that a mixed solution of tea leaf extract and gentian extract reduces hair tingling. Further, Patent Document 4 proposes a hair nourishing cosmetic having an effect of suppressing a feeling of squeaky or rustling by blending a 2-methacryloyloxyethyl phosphorylcholine / butyl methacrylate copolymer solution and a gentian extract. .
"Hair Doctor" by Irwin I Lubowe, published by Hakuyosha, "Proper hair care and bald eradication method", 1962, pages 185-218 "Baldness is healed" by Masashi Inaba, published by Mainichi Shimbun, "The fact and treatment of baldness", published in 1977, pages 97-123 "What works for hair growth and hair growth", published by Katsuyuki Takeda, published by Seishun Publishing Co., Ltd. “TOMOTOMO October issue” written by Shingo Hiira, published by Shin Beauty Publishing Co., “Customers suffering from hair loss ... What advice should I give? ”Published 2005, pp. 75-77 JP, 06-225724, A Claims etc. Japanese Patent No. 3272621 Patent Claim etc. JP 09-077639 A Claims etc. JP, 2008-031129, A Claims etc.

  As mentioned above, although various hair nourishing cosmetics have been developed so far, their hair-growth effect is still not sufficient, and also about the improvement effect of `` Fingering '' and `` Harikoshi '' It was not satisfactory. For these reasons, there has been a need for a hair nourishing cosmetic that has an excellent hair-growth effect, has good fingering during use, and can impart a harsh feeling to the hair. In addition, it is actually desired to suppress the hair feeling caused by the alcohol contained in the hair nourishing cosmetics.

  The present invention has been made by paying attention to the above-mentioned actual situation, and the purpose thereof is to apply hair growth effect by absorption from the scalp by being applied to the head, and hair by adhesion to the hair. It is intended to provide a hair nourishing cosmetic that improves the “finger passage” and “harshness” of the hair, and also exhibits the effect of suppressing the feeling of tingling and rustling of the hair if necessary.

  The hair nourishing cosmetic of the present invention that has achieved the above object has a gist in that it is a blend of a fibroin-derived silk hydrolyzate and a sericin-derived silk hydrolysate. The blend ratio of the fibroin-derived silk hydrolyzate and sericin-derived silk hydrolyzate is 20: 1 to 1: 5, and the total of the fibroin-derived silk hydrolyzate and sericin-derived silk hydrolyzate is the whole hair nourishing cosmetic. It is preferable to mix | blend in the ratio of 0.001 to 2 mass% in the ratio occupied in this, and while being able to suppress a feeling of creaking and a soft feeling, the touching feeling of hair can be improved.

 Further, the hair nourishing cosmetic of the present invention can be blended with at least susabinori or hydrolyzed susabinori, if necessary, and the blending amount of the hair nourishing cosmetic is 0.001 to 0.3% by mass. It is preferable that the hair-growth effect and the harshness can be improved.

  According to the present invention, by blending two types of silk hydrolyzate with a specific blending ratio, the feeling of fingering after applying a hair nourishing cosmetic is improved, and it is possible to suppress the squeaky feeling and the soft feeling of hair. Thus, by incorporating susabinori or hydrolyzed susabinori, a hair nourishing cosmetic capable of exhibiting an excellent hair-growth effect and imparting a harsh feeling to the hair could be realized.

  Inventors examined from various angles in order to solve said subject. As a result, with regard to the problem to hair, by containing two kinds of silk hydrolyzate at a specific blending ratio, it suppresses the sensation of sensation, exhibits excellent fingering feeling, and is mainly used for food. The present invention has been found by applying a hair nourishing cosmetic that also contains susabinori or its hydrolyzate to the head to provide an excellent hair-growth effect and impart a harsh feeling. (Japanese Patent Application No. 2008-170872).

 It is useful that the hair nourishing cosmetic of the present invention contains a fibroin-derived silk hydrolyzate and a sericin-derived silk hydrolyzate. Alcohol, which is a common solvent for hair restorers, tends to induce hair tingling, so these fibroin-derived silk hydrolysates and sericin-derived silk hydrolysates have the effect of suppressing these problems. Is. In order to exert such effects, the blending ratio of the fibroin-derived silk hydrolyzate and the sericin-derived silk hydrolyzate is 20: 1 to 1: 5, and the fibroin-derived silk hydrolyzate and the sericin-derived silk hydrolyzate It is also preferable to blend in a proportion of 0.001 to 2% by mass with respect to the total of the hair nourishing cosmetic.

 However, if the blending ratio of fibroin-derived silk hydrolyzate and sericin-derived silk hydrolyzate is excessive, a sticky feeling will occur when applied to the hair, and the condition of the hair will decrease instead, so 2% by mass or less It is preferable to set it as the ratio to the whole hair nourishing cosmetics.

  On the other hand, susabinori and its hydrolyzate (hydrolyzed susabinori) have been used mainly in foods so far, and are known to have blood pressure lowering action, plasma cholesterol lowering action, etc. by oral administration. Yes. However, there is no example in which Susabinori or its hydrolyzate is used for a hair restorer, a hair growth agent, or a hair nourishing cosmetic, and its effect has not been known. Therefore, according to the study by the present inventors, by applying and applying to the head a hair nourishing cosmetic containing such susabinori or hydrolyzed susabinori, it exhibits an excellent hair restoration effect, It has been found that a “harshness” can be imparted to the hair.

  In order to effectively exhibit the effects as described above, it is preferable to add 0.001% by mass or more (ratio to the total amount of hair nourishing cosmetics) in the case of using hydrolyzed susbinori. However, if the amount of hydrolyzed Susavinori is excessive, a sticky feeling will occur when applied to the hair, and the “harshness” will be reduced instead. (Occupying ratio) is preferable.

 The fibroin-derived silk hydrolyzate is a product obtained by degrading silk to a molecular weight of about 400 by hydrolysis with an enzyme, acid or alkali. A sample containing 20% by weight as a pure component is used.

 The sericin-derived silk hydrolyzate is a product obtained by degrading silk to a molecular weight of about 5500 to 40,000 by hydrolysis with an enzyme, acid or alkali. A sample containing 5.5% by weight as a pure component is used.

 Susavinori contains susavinori whose content of active ingredients is unknown (active ingredients related to hair growth have not yet been specified) and is not completely decomposed in hydrolyzed susavinori. Since an appropriate blending amount is unknown, an appropriate amount may be blended appropriately according to the above criteria.

  The hair nourishing cosmetics of the present invention are fibroin-derived silk hydrolyzate and sericin-derived silk hydrolysate, and susbinori or hydrolyzed susbinori are essential ingredients, but other normal active ingredients contained in hair nourishing cosmetics Or may contain additives. Examples of such active ingredients include cell activators, blood circulation promoters, anti-inflammatory agents, bactericides, and bacteriostatic agents.

  Examples of the cell activator as the active ingredient include pantothenic acid and its derivatives (pantothenyl ethyl ether), N-acetyl-L-methionine, cephalanthin (Tamazaki tsumugi dialkaloid), adenosine triphosphate disodium, potassium aspartate, Photosensitive element No. 301, carrot extract, biotin, mononitroguaiacol, allantoin, pentadecane glyceride, yeast extract, garlic component, pearl protein extract, tiso extract, placenta extract, royal jelly and the like.

  As blood circulation promoters, carpronium chloride, assembly extract, capsicum tincture, cephalanthin, benzyl nicotinate, garlic extract, toki extract, γ-oryzanol, licorice, minoxidil, nematode, chixetsuninjin, ginseng, ginger, jiou, aloe, spironolactone , D-camphor, DL-camphor, DL-α-tocopherol, garlic iodide extract, DL-α-tocopherol linolenate, inositol hexanicotinate, nicotinic acid, DL-α-tocopherol nicotinate, butoxy nicotinate Examples include ethyl, methyl nicotinate, nonanoic acid vanillylamide, DL-α-tocopherol succinate, DL-α-tocopherol acetate, cantharis tincture and ginger tincture. .

  Anti-inflammatory agents include glycyrrhizic acid and its derivatives, glycyrrhetinic acid and its derivatives, fat-soluble glycyrrhetinic acids, licorice extract, azulene, guaiazulene, diphenhydramine and other antihistamines, sicon extract, age extract, oxon extract, chamomile extract, kumaza extract, birch extract Examples include extract, mallow extract, peach leaf extract, yarrow extract, yellow leaf extract, loquat leaf extract, bodaiju extract, hydrocortisone acetate, prednisolone and the like.

  Bactericides and bacteriostatic agents include isopropylmethylphenol, resorcin, triclosan, trichlorocarbanilide, sulfur, photosensitizer 201, benzalkonium chloride, benzethonium chloride, zinc pyrithione, alkyldiaminoethylglycine hydrochloride, salicylic acid, piroctone ora Min, hinokitiol, potassium sorbate, vitamin B6 hydrochloride (pyridoxine hydrochloride), phenol and the like.

  As additives for hair nourishing cosmetics, humectants, pigments, fragrances, preservatives, keratolytic agents, antioxidants, pH adjusting agents, acid / alkali agents, and the like can be appropriately blended.

  Examples of the humectant include polyhydric alcohols such as 1,3-butylene glycol, propylene glycol, and glycerin, collagen, collagen degrading peptide, elastin degrading peptide, keratin degrading peptide, soybean proteolytic peptide, wheat proteolytic peptide, Proteins and peptides such as casein-degrading peptides and derivatives thereof, amino acids such as arginine, serine, glycine, glutamic acid, trimethylglycine, aloe extract, plant extract components such as hamamelis water, loofah water, chamomile extract, licorice extract, Examples include sodium hyaluronate, citrate, chondroitin sulfate, sodium lactate, sodium 2-pyrrolidone-5-carboxylate and the like.

  Examples of the preservative include p-hydroxybenzoic acid esters, benzoates, phenoxyethanol, quaternary ammonium salts and the like.

  pH adjusters / acids / alkali agents include phosphoric acid, malic acid, tartaric acid, carbonic acid, fumaric acid, citric acid, lactic acid, glycolic acid, succinic acid, hydrochloric acid, sulfuric acid, nitric acid or salts thereof, sodium hydroxide, water Examples thereof include potassium oxide, disodium hydrogen phosphate, monoethanolamine, diethanolamine, triethanolamine, arginine, aqueous ammonia, aminomethylpropanol, and salts thereof.

  As the solvents for dissolving the hair nourishing cosmetic of the present invention, water, ethanol and decamethylcyclopentasiloxane are generally used. In addition to these, lower alcohols such as 2-propanol should be used. Can do. The dosage form of the hair nourishing cosmetic of the present invention is useful in liquid form.

  Next, the present invention will be described more specifically by way of examples. However, the following examples are not intended to limit the present invention, and all modifications can be made without departing from the spirit of the above and following descriptions. To be included in the scope.

[Example 1]
(Sensory evaluation method for finger feeling)
Each sample (formulation examples 1 to 19) shown in the following Tables 1 to 4 was applied to a hair bundle not subjected to chemical treatment (for example, permanent treatment or hair color treatment) at a bath ratio of 1: 1. After the hair bundle is naturally dried, the sense of fingering of the hair bundle is sensorially evaluated by the 10 panelists in the following three stages (evaluation points: 1 to 3 points), and the total is obtained and evaluated according to the following evaluation criteria. did. The results are shown in Tables 1-4.

  3 points: The feeling of fingering was clearly improved compared to before treatment.

  2 points: Slightly improved feeling of fingering compared to before treatment.

  1 point: No improvement in touch feeling was observed compared to before treatment.

[Evaluation criteria for feeling of fingering hair]
◎: 26 to 30 points ○: 21 to 25 points Δ: 16 to 20 points ×: 10 to 15 points [Example 2]
(Sensory evaluation method for the effect of suppressing tingling)
Each sample (formulation examples 1 to 19) shown in Tables 1 to 4 below was applied to a hair bundle not subjected to chemical treatment so as to have a bath ratio of 1: 1. After the hair bundle was naturally dried, the feeling of squeaking of the hair bundle was subjected to sensory evaluation in the following three stages (evaluation points: 1 to 3 points) with 10 professional panelists, and the total was obtained and evaluated according to the following evaluation criteria. . The results are shown in Tables 1-4.

  3 points ... I didn't feel any tingling.

  2 points ... I didn't feel any tingling.

  1 point ... I felt a squeaky feeling.

[Evaluation Criteria for Suppressing Effect of Hair's Kishimi-sense]
◎: 26-30 points ○: 21-25 points △: 16-20 points ×: 10-15 points

 As is clear from this result, if the blending ratio of the fibroin-derived silk hydrolyzate and the sericin-derived silk hydrolyzate is in the range of 20: 1 to 1: 5 (formulation examples 2 to 9), the hair feels squeaky. It can be seen that a good finger feeling can be obtained. Moreover, in the ratio which the sum total of a fibroin origin silk hydrolyzate and a sericin origin silk hydrolyzate occupies for the whole hair nourishing cosmetics, if it is a ratio (prescription examples 14-18) of hair, It can be seen that the feeling of squeaking can be suppressed and a good fingering feeling can be obtained. When the blending ratio of the fibroin-derived silk hydrolyzate and the sericin-derived silk hydrolyzate is 0.001% by mass or less (Formulation Example 13), a sufficient effect cannot be obtained. When it is done, a sticky feeling is produced, and the condition of the hair is lowered instead. Therefore, it is preferably 2% by mass or less (ratio to the entire hair nourishing cosmetic).

[Example 3]
(Evaluation method for hair growth effect)
As test animals, 6 week old C3H / He male mice (10 to 15 mice per group) were preliminarily raised for 1 week, and the day before the test, the skin surface of the animal's back about 8 cm ² under ether anesthesia was used for animals. The hair was shaved with an electric clipper (manufactured by Natsume Seisakusho Co., Ltd.) so as not to damage the skin. The samples shown in Table 5 below (Prescription Examples 3, 20 to 22) were applied to each back skin of the hair-removed animal once a day, every day except Saturdays and Sundays. The amount applied at one time was 150 μL / time, and after dropping with a micropipette, the whole part was spread with a fluororesin rod. The evaluation of hair regeneration was performed based on the daily change in the area ratio of the hair regeneration part to the hair removal part (hair growth area (%)).

  The hair growth area (%) was determined by the following procedure. From the time when hair growth was confirmed, a photograph of the application site was taken using a digital camera every day. Thereafter, the image was read by image processing software “Image J”, the entire application site and the hair growth site were selected using a pen tablet, and the area of each site was measured by the number of pixels. The hair growth area (%) was calculated from the number of pixels (s) of the hair growth site and the number of pixels (S) of the entire application site using the following formula (1). The results are also shown in Table 5.

   Hair growth area (%) = s / S × 100 (1)

 As is clear from these results, in Formulation Examples 3, 21, and 22 in which the hydrolyzed Susavinori was blended, a clear hair-growth effect was observed (indicated by “◯” in Table 5), and the formulation in which the hydrolyzed Susavinori was not blended In Example 20, it can be seen that the hair-growth effect is reduced (indicated by “x” in Table 5). That is, hydrolyzed Susavinori has a higher hair-growth effect than fibroin-derived silk hydrolyzate and sericin-derived silk hydrolyzate.

[Evaluation criteria for hair growth effect]
○: Hair growth area 35 days after application is 70% or more ×: Hair growth area 35 days after application is less than 70% [Example 4]
(Measurement method of elasticity of hair: confirmation test 1 of harshness)
Hair not subjected to chemical treatment was aligned to a length of 10 cm (weight: 0.125 g), and left for 12 hours at a temperature of 20 ° C. and a humidity of 60%. Subsequently, the following test was performed in a room with a temperature of 20 ° C. and a humidity of 60%. 0.125 g of each sample (Prescription Examples 23 to 34) shown in Tables 6 and 7 below was applied to the hair bundle. After wiping off the sample with a towel so that the total amount of the hair bundle and the sample is 0.1375 g, fix the hair bundle in parallel with the ground, apply a ruler from the vertical surface to the ground, and pull the hair bundle by gravity. The degree of drooping (measurement of elasticity) was measured at the center of the hair tip and evaluated according to the following criteria. Since such elasticity can be consistent with normal harshness, this evaluation criterion was used. The results are shown in Tables 6 and 7 below.

[Evaluation Criteria 1 for Harnessing Effect on Hair]
◎: Elasticity measurement value is 7.4 cm or more ○: Elasticity measurement value is 7.2 cm or more and less than 7.4 cm Δ: Elasticity measurement value is 7.0 cm or more and less than 7.2 cm ×: Elasticity measurement value is Less than 7.0 cm (Measurement method of bending stiffness of hair: confirmation test 2 of harshness)
(A) Target hair Using hair that has not undergone chemical treatment, the hair diameter [major axis (mm) and minor axis (mm)] is measured with a “hair diameter measurement system” (manufactured by Kato Tech Co., Ltd.), and the hair The cross section (mm ² ) was obtained from the following formula (2).

Cross section (mm ² ) = (π / 4) × major axis (mm) × minor axis (mm) (2)
At this time, eight hairs having the same cross-sectional area were selected, and the hairs were affixed on a 12-mm-wide vinyl chloride plate to prepare a bending stiffness measuring hair bundle (measuring hair bundle). In the measurement, the bending rigidity per hair was calculated.

(B) Initial value measurement (initial value measurement was performed to select a hair bundle having the same characteristics)
(1) Treatment of hair: Formulation Examples 23 to 34 were applied to the measurement hair bundle at a bath ratio of 1: 1.

  (2) Hair conditioning: The hair bundle for measurement was conditioned at (20 ° C., humidity 60%) for 24 hours or more.

  (3) Measuring equipment and conditions: A single hair bending tester “KES-SH” (manufactured by Kato Tech Co., Ltd.) was used for the measurement.

(4) The measurement was performed under conditions of a maximum curvature of 2 cm ⁻¹ , a torque sensitivity of 1.0 (1.00 gf · cm), and a maximum displacement speed range of 5 (0.42 cm ⁻¹ / sec). The evaluation criteria at this time are as follows. The results are shown in Tables 6 and 7 below.

[Evaluation criteria 2 for the effect of imparting a firmness to hair]
A: Bending rigidity per hair is 190 mgf · cm ² or more ○: Bending rigidity per hair is 185 mgf · cm ² or more and less than 190 mgf · cm ² Δ: Bending rigidity per hair is 180 mgf · cm ² As described above, less than 185 mgf · cm ² ×: Flexural rigidity per hair is less than 180 mgf · cm ² (Sensory evaluation method of harshness imparting effect: harshness confirmation test 3)
Each sample (formulation example 23, 27-34) shown in the following Table 7 was applied to the hair bundle not subjected to chemical treatment so as to have a bath ratio of 1: 1. After the hair bundle was naturally dried, the sense of firmness of the hair bundle was subjected to sensory evaluation in the following three stages (evaluation points: 1 to 3 points) with 10 professional panelists, and the total was obtained and evaluated according to the following evaluation criteria. . The results are also shown in Table 7.

  3 points: The sharpness was clearly improved compared to before treatment.

  2 points: The feeling of elasticity improved slightly compared to before treatment.

  1 point: No improvement in harshness was observed compared to before treatment.

[Evaluation criteria 3 for the effect of imparting harshness to hair]
◎: 26-30 points ○: 21-25 points △: 16-20 points ×: 10-15 points

 As is clear from this result, when hydrolyzed Susavinori is blended in an amount of 0.033 to 10.0% by mass (in terms of pure content: 0.001 to 0.3%) (Prescription Examples 23 and 28 to 32), The effect of imparting a firmness is high. However, it can be seen that when the blending ratio of hydrolyzed Susavino is excessive (Prescription Examples 33 and 34), a sticky feeling is produced.

Claims (5)

  A hair nourishing cosmetic characterized by comprising a fibroin-derived silk hydrolyzate and a sericin-derived silk hydrolyzate.   The hair nourishing cosmetic according to claim 1, wherein a blending ratio of the fibroin-derived silk hydrolyzate and sericin-derived silk hydrolyzate is 20: 1 to 1: 5.   The hair nourishing cosmetic according to claim 1 or 2, wherein the total amount of the fibroin-derived silk hydrolyzate and the sericin-derived silk hydrolyzate is 0.001 to 2% by mass in the total proportion of the hair nourishing cosmetic.   The hair nourishing cosmetic according to any one of claims 1 to 3, wherein at least susabinori or hydrolyzed susabinori is blended.   The hair nourishing cosmetic according to any one of claims 1 to 4, wherein a proportion of the blended amount of the hydrolyzed susabinori to the entire hair nourishing cosmetic is 0.001 to 0.3% by mass.