Sanitary product carrying lactoferrin

Abstract

To provide a method by which disorder of a vagina bacterial flora during menstrual period is prevented to improve the vagina bacterial flora.SOLUTION: One aspect of the present invention is a sanitary product carrying lactoferrin or a composition including lactoferrin and an additive. The sanitary product and a kit including lactoferrin or the composition including lactoferrin and the additive are also provided.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a sanitary product that can be used to improve the disruption of the vaginal bacterial flora during menstruation. [Background technology]

[0002] It is known that oral or topical administration of lactoferrin improves the female reproductive tract bacterial flora to a healthy state. It has been reported that administering lactoferrin vaginal preparations to patients with intractable vaginosis results in a Lactobacillus-dominated vaginal flora, improving symptoms (Non-Patent Documents 1, 2, and 3). Meanwhile, it is known that the vaginal bacterial flora fluctuates with the menstrual cycle (Non-Patent Document 4). Hormonal changes just before and during menstruation and during pregnancy can reduce vaginal acidity, facilitating the proliferation of bacteria that cause infections. Under normal, healthy conditions, women of childbearing age have a Lactobacillus-dominated vaginal flora. However, it has been reported that the bacterial flora diversifies during menstruation, returning to the original Lactobacillus-dominated state upon menstruation, repeating this cycle (Non-Patent Document 5). The speed at which the bacterial flora returns to its original state varies depending on the individual's health condition, age, etc., but if the disruption of the bacterial flora during menstruation can be restored to its original Lactobacillus-dominant state as quickly as possible, it is believed that the risk of contracting vaginal infections caused by other microorganisms can be reduced accordingly. Furthermore, recent research has shown that disruption of the bacterial flora in the female reproductive tract is one of the causes of infertility, and normalization of the bacterial flora is an important factor for normal pregnancy and childbirth (Non-Patent Document 2). However, to date, there have been no reports of agents or methods for improving the bacterial flora that focus on the deterioration of the bacterial flora during menstruation. [Prior art documents] [Non-patent literature]

[0003] [Non-Patent Document 1] Pino A et al., Microbial Ecology in Health and Disease, 2017, 28,1-11,1357417 Bacterial biota of women with bacterial vaginosis treated with lactoferrin, open prospective randomized trial. [Non-patent document 2] Otsuki K. et al., Biochem. Cell Biol.2017, 95, 31-33, Effects of lactoferrin in 6 patients with refractory bacterial vaginosis. [Non-patent document 3] Sessa R. et al., Biochem. Cell Biol.2016, 00, 1-7, Effect of bovine lactoferrin on Chlamydia trachomatis infection and inflammation. [Non-patent document 4] Fujisawa T. et al., Bifidobacteria Microflora, 1992,11, 1, 33-38, Effect of Menstrual Cycle and Different Age on Vaginal Microflora of Healthy Women. [Non-Patent Document 5] Hickey RJ. et al., Int. J. Obstetrics and Gynaecology, 2013, 695-706, Effects of tampons and menses on the composition and diversity of vaginal microbial communities over time. [Non-patent document 6] Walters, W. et al., mSystems, 2016; 1(1), e00009-15. Improved bacterial 16S rRNA gene (V4 and V4-5) and fungal internal transcribed spacer marker gene primers for microbial community surveys. [Non-Patent Document 7] Kyono K et al., Reprod Med Biol. Jul; 17(3): 297-306. Analysis of endometrial microbiota by 16S ribosomal RNA gene sequencing among infertile patients: a single-center pilot study. Summary of the Invention [Problem to be solved by the invention]

[0004] An object of the present invention is to provide a method for improving the disturbance of vaginal bacterial flora during menstruation. [Means for solving the problem]

[0005] As a result of intensive research aimed at solving the above problems, the present inventors discovered that the deterioration of the vaginal bacterial flora can be prevented or improved by directly administering lactoferrin into the vagina during menstruation, leading to the completion of the present invention. That is, by using a sanitary product carrying lactoferrin or a composition containing lactoferrin and an auxiliary substance, the growth of iron-requiring bacteria that occurs during menstruation is inhibited by lactoferrin, an iron-binding protein, thereby preventing disruption of the vaginal bacterial flora during menstruation and improving the vaginal bacterial flora.

[0006] According to the present invention, the following is provided: [1] A sanitary product carrying lactoferrin or a composition containing lactoferrin and an auxiliary substance. [2] The sanitary product according to [1] above, wherein the sanitary product is a tampon or a napkin. [3] The sanitary product according to [1] or [2] above, wherein the composition is in the form of a powder, an oily liquid, or an oily semi-solid. [4] The sanitary product according to any one of [1] to [3] above, wherein the amount of lactoferrin in the composition is 0.1 to 99.9% by weight of the composition. [5] The sanitary product according to any one of [1] to [4] above, wherein the amount of lactoferrin in the composition is 1 to 99% by weight of the weight of the composition. [6] The sanitary product according to any one of [1] to [5] above, wherein the amount of lactoferrin in the composition is 10 to 90% by weight of the weight of the composition. [7] The sanitary product according to any one of [1] to [6] above, characterized in that the amount of lactoferrin carried in the sanitary product is 5 to 1,000 mg / piece. [8] The sanitary product according to any one of [1] to [7] above, characterized in that the amount of lactoferrin carried in the sanitary product is 10 to 500 mg / piece. [9] The sanitary product according to any one of [1] to [8] above, characterized in that the amount of lactoferrin carried in the sanitary product is 20 to 200 mg / piece.

[10] A kit comprising a sanitary product and a composition comprising lactoferrin or lactoferrin and an auxiliary substance.

[11] The kit according to

[10] above, wherein the sanitary product is a tampon or a napkin.

[12] A method for improving the disruption of vaginal bacterial flora during menstruation by using the sanitary products described in [1] to [9] above. [Effects of the Invention]

[0007] The sanitary product of the present invention quickly normalizes the disturbance of the vaginal flora during menstruation. [Brief explanation of the drawings]

[0008] [Figure 1]FIG. 10 is a diagram showing an embodiment of preparing the sanitary product of the present invention by incorporating lactoferrin, or a composition containing lactoferrin and an auxiliary substance, between the thin layers of the absorbent portion during the molding stage of the sanitary product. [Figure 2] FIG. 10 is a diagram showing an embodiment of preparing the sanitary product of the present invention by incorporating lactoferrin, or a composition containing lactoferrin and an auxiliary substance, between the thin layers of the absorbent portion during the molding stage of the sanitary product. [Figure 3] FIG. 1 shows an embodiment of preparing the sanitary product of the present invention by dripping or spraying a composition containing lactoferrin and an auxiliary substance into the absorbent part of a molded sanitary product to impregnate it. [Figure 4] FIG. 1 shows an embodiment of preparing the sanitary product of the present invention by dripping or spraying a composition containing lactoferrin and an auxiliary substance into the absorbent part of a molded sanitary product to impregnate it. [Figure 5] FIG. 10 is a diagram showing an embodiment of preparing the sanitary product of the present invention by impregnating an absorbent body with a composition containing lactoferrin and an auxiliary substance immediately before use of the sanitary product. [Figure 6] FIG. 10 is a diagram showing an embodiment of preparing the sanitary product of the present invention by impregnating an absorbent body with a composition containing lactoferrin and an auxiliary substance immediately before use of the sanitary product. [Figure 7] FIG. 10 is a diagram showing an embodiment of preparing the sanitary product of the present invention by applying a composition containing lactoferrin and an auxiliary substance to an absorbent body immediately before use of the sanitary product. [Figure 8] FIG. 10 is a diagram showing an embodiment of preparing the sanitary product of the present invention by applying a composition containing lactoferrin and an auxiliary substance to an absorbent body immediately before use of the sanitary product. [Figure 9] FIG. 10 is a diagram showing an embodiment of preparing the sanitary product of the present invention by injecting a composition containing lactoferrin and an auxiliary substance into the gap between the applicator, which is an insertion aid for the sanitary product, and the absorbent body immediately before use. DETAILED DESCRIPTION OF THE INVENTION

[0009] Any lactoferrin can be used in the present invention as long as it improves the vaginal flora. Lactoferrin is a polymer with a molecular weight of approximately 80,000 and has the ability to chelate with two trivalent iron ions. The "lactoferrin" used in the present invention includes all forms, from iron-free to completely saturated with iron ions. Furthermore, any lactoferrin can be used in the present invention, regardless of its origin. For example, lactoferrin extracted from mammalian milk such as humans or cows, and recombinant lactoferrin or its salts produced by genetic engineering can be used. Commercially available lactoferrin purified from cow's milk is available from suppliers such as Morinaga Milk Industry (Japan), Tatura (Australia), and Tatua (New Zealand). A method for purifying lactoferrin from milk is disclosed in detail in, for example, U.S. Patent No. 9,115,211 (issued August 25, 2015). Essentially, lactoferrin contained in skim milk or whey can be easily purified by adsorbing and desorbing it onto a cation exchange resin, followed by steps such as desalting, freeze-drying, or spray-drying.

[0010] In the present invention, one type of lactoferrin may be used alone, or two or more types may be used in combination.

[0011] The sanitary products of the present invention contain lactoferrin or a composition containing lactoferrin and an auxiliary substance. In either case, the lactoferrin content per sanitary product can be any amount within the range that quickly normalizes the disruption of vaginal bacterial flora during menstruation, but is preferably 5 to 1,000 mg / product, more preferably 10 to 500 mg / product, and particularly preferably 20 to 200 mg / product.

[0012] The amount of lactoferrin in the composition contained in the sanitary product of the present invention can be selected as desired within a range that quickly normalizes the disruption of vaginal bacterial flora during menstruation, and is preferably 0.1 to 99.9 wt% of the weight of the composition, more preferably 1 to 99 wt% of the weight of the composition, and particularly preferably 10 to 90 wt% of the weight of the composition.

[0013] The auxiliary substance contained in the composition carried in the sanitary product of the present invention may be in the form of a powder, granules, oily solid, oily semi-solid, oily liquid, or the like. As such auxiliary substances, the components and additives exemplified below may be selected and used in combination as desired within the scope that does not impair the effects of the present invention. (1) Various oils and fats Avocado oil, almond oil, fennel oil, perilla oil, olive oil, orange oil, orange roughage oil, sesame oil, cacao butter, chamomile oil, carrot oil, cucumber oil, beef tallow fatty acids, kukui nut oil, safflower oil, shea butter, liquid shea butter, soybean oil, camellia oil, corn oil, rapeseed oil, persic oil, castor oil, cottonseed oil, peanut oil, turtle oil, mink oil, egg yolk oil, palm oil, palm kernel oil, Japan wax, coconut oil, beef tallow, lard, squalene, squalane, pristane, and hydrogenated products of these oils and fats (such as hardened oils). (2) Waxes Beeswax, carnauba wax, spermaceti, lanolin, liquid lanolin, reduced lanolin, hard lanolin, candelilla wax, montan wax, shellac wax, rice wax, etc. (3) Mineral oil Liquid paraffin, Vaseline, paraffin, ozokeride, ceresin, microcrystalline wax, etc. (4) Fatty acids Natural fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, linoleic acid, linolenic acid, docosahexaenoic acid, eicosapentaenoic acid, 12-hydroxystearic acid, undecylenic acid, tall oil, and lanolin fatty acids; and synthetic fatty acids such as isononanoic acid, caproic acid, 2-ethylbutanoic acid, isopentanoic acid, 2-methylpentanoic acid, 2-ethylhexanoic acid, and isopentanoic acid. (5) Alcohol Natural alcohols such as ethanol, isopropanol, lauryl alcohol, cetanol, stearyl alcohol, oleyl alcohol, lanolin alcohol, cholesterol, phytosterol, and phenoxyethanol; and synthetic alcohols such as 2-hexyldecanol, isostearyl alcohol, and 2-octyldodecanol. (6) Polyhydric alcohols Ethylene oxide, ethylene glycol, diethylene glycol, triethylene glycol, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, polyethylene glycol, propylene oxide, propylene glycol, polypropylene glycol, 1,3-butylene glycol, pentyl glycol, glycerin, pentaerythritol, threitol, arabitol, xylitol, ribitol, galactitol, sorbitol, mannitol, lactitol, maltitol, and the like. (7) Esters Isopropyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, oleyl oleate, decyl oleate, octyldodecyl myristate, hexyldecyl dimethyloctanoate, cetyl lactate, myristyl lactate, diethyl phthalate, dibutyl phthalate, lanolin acetate, ethylene glycol monostearate, propylene glycol monostearate, propylene glycol dioleate, etc. (8) Gums, sugars or polymeric compounds Gum arabic, xanthan gum, gum benzoin, gum dammar, guaiac butter, Irish moss, gum karaya, gum tragacanth, carob gum, quince seed, agar, casein, lactose, fructose, sucrose or its esters, trehalose or its derivatives, dextrin, gelatin, pectin, starch, carrageenan, carboxymethyl chitin or chitosan, hydroxyalkyl (C2-C4) chitin or chitosan to which an alkylene (C2-C4) oxide such as ethylene oxide has been added, low molecular weight chitin or chitosan, chitosan salt, sulfated chitin or chitosan, phosphorylated chitin or chitosan, alginic acid or its salt, hyaluronic acid or its salt, chondroitin sulfate or its salt, Heparin, ethyl cellulose, methyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, carboxyethyl cellulose, sodium carboxyethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, nitrocellulose, crystalline cellulose, polyethylene, polyvinyl alcohol, polyvinyl methyl ether, polyvinylpyrrolidone, polyvinyl methacrylate, polyacrylates, polyalkylene oxides such as polyethylene oxide and polypropylene oxide or crosslinked polymers thereof, carboxyvinyl polymers, polyethyleneimine, silicone, polysiloxane, etc.

[0014] As described above, the composition carried by the sanitary product of the present invention can contain lactoferrin and auxiliary substances, and if necessary, any of the various solvents, preservatives, solubilizers, stabilizers, etc. commonly used in pharmaceuticals and cosmetics can be added in amounts that will quickly normalize the disruption of the vaginal bacterial flora during menstruation.Other drugs may also be added if necessary.

[0015] The composition carried by the sanitary product of the present invention is preferably in a dosage form convenient for intravaginal administration, such as a powder, oily liquid, or oily semisolid, and can be prepared by mixing and stirring the lactoferrin and auxiliary substances described above. Note that, because lactoferrin is unstable at high temperatures and humidity, the composition is preferably prepared in a dry state.

[0016] The sanitary product of the present invention can be in any form that allows lactoferrin to be delivered into the vagina, such as a tampon or napkin. When the sanitary product of the present invention is a tampon or napkin, the lactoferrin content therein can be any amount within the range that quickly normalizes the disruption of vaginal bacterial flora during menstruation, but is preferably 5 to 1,000 mg / unit, more preferably 10 to 500 mg / unit, and particularly preferably 20 to 200 mg / unit.

[0017] The sanitary product of the present invention can be prepared by loading lactoferrin or a composition containing lactoferrin and an auxiliary substance onto a sanitary product such as a tampon or napkin. The loading method includes the following methods. The following methods are intended to illustrate the present invention and are not intended to limit the present invention in any way. 1. Lactoferrin alone, for example, 0.2 g of lactoferrin, is airtightly enclosed between the thin layers of the absorbent body during the molding process of the sanitary product (Figure 1) (Figure 2). 2. A composition containing lactoferrin and auxiliary substances, for example, 0.1 g of a powder containing 90% by weight of lactoferrin, is airtightly enclosed between the thin layers of the absorbent body during the molding process of the sanitary product (Figure 1) (Figure 2). 3. A composition containing lactoferrin and an auxiliary substance, for example, 0.5 g of an oily liquid containing 20% ​​by weight of lactoferrin, is watertightly enclosed between the thin layers of the absorbent body during the molding process of the sanitary product (Figure 1) (Figure 2). 4. A composition containing lactoferrin and an auxiliary substance, for example, 1 g of an oily liquid containing 10% by weight of lactoferrin, is dripped or sprayed onto the absorbent portion of the molded sanitary product to impregnate it (Figure 3) (Figure 4). 5. A composition containing lactoferrin and an auxiliary substance, for example, 0.2 g of an oily liquid containing 20% ​​by weight of lactoferrin, is impregnated into the absorbent material of the sanitary product immediately before use (Figure 5) (Figure 6). 6. Apply 0.4 g of a composition containing lactoferrin and an auxiliary substance, for example, an oily semi-solid preparation containing 10% by weight of lactoferrin, to the absorbent material of the sanitary product immediately before use (Figure 7) (Figure 8). 7. Immediately before use, inject 0.2 g of a composition containing lactoferrin and an auxiliary substance, such as an oily liquid or semi-solid containing 20% ​​by weight of lactoferrin, into the gap between the applicator, which is the insertion aid for the sanitary product, and the absorbent body (Figure 9).

[0018] Sanitary products containing the lactoferrin of the present invention or a composition containing lactoferrin and an auxiliary substance can be used depending on the menstrual condition. For example, 4 to 5 tampons and 7 to 18 napkins can be used per day throughout the menstrual period. [Example]

[0019] The present invention will be described in more detail below with reference to examples. [Example]

[0020] Compositions containing lactoferrin and auxiliary substances Various compositions were prepared for use in the sanitary product of the present invention. Examples of formulations are shown below, but because they were prepared by mixing and stirring, only the amounts included are shown. Appropriate amounts of lactoferrin (manufactured by Tatura, Australia) and auxiliary substances (various oils and fats, waxes, mineral oils, fatty acids, alcohols, polyhydric alcohols, esters, gums, sugars, polymeric compounds, etc.) were mixed together. The lactoferrin content ranged from 0.1 to 90% by weight. Specific formulation examples are shown below. (Formulation Example 1) Oily semi-solid agent Lactoferrin 10% Liquid paraffin 75% Sodium carboxymethylcellulose 8% Polyethylene 6% Pectin 1% (Formulation example 2) Oily semi-solid agent Lactoferrin 40% Vaseline 60% (Formulation example 3) Oily liquid Lactoferrin 0.1% Liquid paraffin 99.9% (Formulation example 4) Oily liquid Lactoferrin 20% Butylene Glycol 8% Glycerin 72% (Formulation example 5) Oily liquid Lactoferrin 30% Squalane 70% (Prescription Example 6) Powder Lactoferrin 80% Hydroxypropyl methylcellulose 20% (Prescription Example 7) Powder Lactoferrin 90% Xanthan gum 10% [Example]

[0021] Loading of lactoferrin or a composition containing lactoferrin and an auxiliary substance into sanitary products (lactoferrin) 0.1 g of lactoferrin (Tatura, Australia) was added between the layers of the absorbent body during the tampon molding process, and the absorbent body was then molded into a cylindrical shape and compressed to obtain the tampon of the present invention (Figure 1). (lactoferrin) 0.2 g of lactoferrin (manufactured by Tatura, Australia) was added between the thin layers of the absorbent body during the shaping stage of the napkin, and then the napkin of the present invention was obtained (Figure 2). (oil-based liquid) 20 g of lactoferrin (Tatura, Australia) was added to 80 g of squalane and stirred to prepare a composition. 0.5 g of the composition was added dropwise or sprayed onto the absorbent portion of a molded tampon to obtain the tampon of the present invention (Figure 3). (oil-based liquid) 10 g of lactoferrin (Tatura, Australia) was added to 90 g of liquid paraffin and stirred to prepare a composition. 2 g of the composition was added dropwise or sprayed onto the absorbent portion of a molded napkin to obtain the napkin of the present invention (Figure 4). (oil-based semi-solid agent) A composition was prepared by adding 10 g of lactoferrin (manufactured by Tatura, Australia), 8 g of cellulose gum, 6 g of polyethylene, and 1 g of pectin to 75 g of liquid paraffin and mixing them. Just before using a tampon (with applicator), 0.38 g of the composition was injected into the gap between the applicator and the absorbent body to obtain a tampon of the present invention (FIG. 9). [Example]

[0022] Clinical trials The clinical trial involved subjects who agreed to participate in the study, and compared the vaginal flora before and after using lactoferrin-infused tampons during three menstrual cycles over a nine-week period. The lactoferrin-infused tampon was prepared by injecting 0.38 g (equivalent to 38 mg of lactoferrin) of the oily semi-solid formulation of Formulation Example 1 containing 10% by weight of lactoferrin (manufactured by Tatura, Australia) into the gap between the applicator and absorbent body of a Sofy Soft Tampon Regular (manufactured by Unicharm Corporation). The subjects began using lactoferrin-infused tampons from the second or third menstrual cycle and changed the tampons every four hours. Samples were collected by self-collection using a swab brush (trade name "OMNIgene VAGINAL" (DNA Genotek Inc., Canada)) from a vaginal flora DNA collection kit. The collected vaginal mucosal fluid was transferred to 1 ml of a preservative solution (trade name "MMB collection tube" (DNA Genotek Inc., Canada)) for bacterial inactivation and stabilization, and stored at room temperature. Subject 1 refrained from consuming foods containing lactic acid bacteria and fermented foods as much as possible from the start of her first menstruation before the intervention, and samples were taken on the seventh day of menstruation.She then used lactoferrin-infused tampons during her second and third menstrual cycles, and samples were taken on the seventh day of menstruation for each cycle.The results showed that use of lactoferrin-infused tampons increased vaginal Lactobacillus% during the third menstrual cycle (Table 1).

[0023] [Table 1]

[0024] The long-term effects were further examined in Subject 2. Subject 2 used lactoferrin-infused tampons from the first menstrual cycle, and samples were collected on the seventh day of menstruation for three cycles. The results showed that the use of lactoferrin-infused tampons for three cycles resulted in an increase in vaginal Lactobacillus% (Table 2).

[0025] [Table 2]

[0026] In Example 3, vaginal bacterial flora analysis was carried out as follows. Self-collected vaginal mucosal fluid was transferred to 1 ml of a preservative solution for bacterial inactivation and stabilization (MMB collection tube, DNA Genotek Inc., Canada). To extract bacterial genomic DNA, proteinase K and lysozyme were added to the preservative solution to lyse the bacteria. Genomic DNA was extracted using a DNA extraction kit (Agencourt Genfind v2 Blood & Serum DNA Isolation Kit, Beckman Coulter Inc., USA). The concentration of the extracted DNA was measured using the Qubit dsDNA HS Assay Kit (ThermoFisher Scientific KK).Bacterial flora analysis was performed using 16S amplicon sequencing with a next-generation sequencer. Based on the Earth Microbiome Project protocol (Non-Patent Document 6), bacterial DNA was amplified using primers consisting of a sequence amplifying the V4 region of the 16S rRNA gene and an Illumina Nextera XT adapter sequence (Non-Patent Document 7). For PCR, a mixture of 25 ng / μL DNA, 200 μmol / L of each deoxyribonucleotide triphosphate, 400 nmol / L of each primer, 2.5 U of FastStart HiFi polymerase, 20 mg / mL BSA (Sigma), and a buffer containing 0.5 mol / L betaine (Sigma) and MgCl2 (Roche) was prepared. PCR was performed using a thermal cycler (SimpliAmp Thermal Cycler, Thermo Fisher Scientific). After denaturation at 94°C for 2 minutes, 30 cycles of 94°C for 20 seconds, 50°C for 30 seconds, and 72°C for 1 minute were performed, followed by a final reaction at 72°C for 5 minutes. PCR products were purified using Agencourt AMPure XP (Beckman Coulter Inc., USA). Libraries were then prepared using the Nextera XT Index kit (Illumina Inc., USA) according to the Illumina 16S Metagenomic Sequencing Library Preparation protocol (https: / / support.illumina.com / documents / documentation / chemistry_documentation / 16s / 16s-metagenomic-library-prep-guide-15044223-b.pdf). The prepared library was sequenced by 2 × 200-bp paired-end sequencing using a kit with the trade name "MiSeq Reagent Kit v3" (Illumina KK).Data analysis involved checking the quality of the entire sequence using “fastqQC” ( https: / / www.bioinformatics.babraham.ac.uk / projects / fastqc / ), and fungal genus-level identification using “USEARCH” ( https: / / www.drive5.com / usearch / ) and “QIIME” ( http: / / qiime.org / ).

[0027] This application is based on Japanese patent application No. 2020-013871 filed on January 30, 2020, and all contents described in the specification and claims of No. 2020-013871 are incorporated herein by reference.

Claims

[Claim 1] A sanitary product carrying lactoferrin or a composition containing lactoferrin and an auxiliary substance.

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