WO2015043115A1 - 阿胶或阿胶深加工物质在制备改善发质的组合物中的应用 - Google Patents

阿胶或阿胶深加工物质在制备改善发质的组合物中的应用 Download PDF

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WO2015043115A1
WO2015043115A1 PCT/CN2014/000868 CN2014000868W WO2015043115A1 WO 2015043115 A1 WO2015043115 A1 WO 2015043115A1 CN 2014000868 W CN2014000868 W CN 2014000868W WO 2015043115 A1 WO2015043115 A1 WO 2015043115A1
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hair
ejiao
gelatin
deep processing
skin
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PCT/CN2014/000868
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English (en)
French (fr)
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周祥山
尤金花
田守生
嵇传良
张淹
王春艳
张路
李民
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山东东阿阿胶股份有限公司
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Priority to JP2016543292A priority Critical patent/JP6301479B2/ja
Priority to US15/024,381 priority patent/US9775794B2/en
Priority to KR1020167007919A priority patent/KR20160046897A/ko
Publication of WO2015043115A1 publication Critical patent/WO2015043115A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A61K8/65—Collagen; Gelatin; Keratin; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/36—Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/98—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
    • A61K8/981—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin of mammals or bird
    • A61K8/985—Skin or skin outgrowth, e.g. hair, nails
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/002—Preparations for repairing the hair, e.g. hair cure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/14—Extraction; Separation; Purification
    • C07K1/36—Extraction; Separation; Purification by a combination of two or more processes of different types
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/78—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P21/00—Preparation of peptides or proteins
    • C12P21/06—Preparation of peptides or proteins produced by the hydrolysis of a peptide bond, e.g. hydrolysate products
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof

Definitions

  • the present invention relates to new uses of Ejiao or Ejiao deep processing products, and in particular to the use of Ejiao or Ejiao deep processing materials in the preparation of compositions for improving hair quality.
  • Hair damage can be divided into the following types according to the factors: 1) physical damage: the daily hair combing, the pulling force of the straightening hair and the friction caused by the hair surface covered by the hair surface of the hair scales; 2) Chemical damage: perm, hair dye, bleach and other substances destroy the hair oil layer, penetrate the hair small scales into the fur, causing keratin disulfide bond rupture, resulting in hair hydrophobicity, strength and elasticity; 3) thermal damage :Hot hair or electric perm causes the hair to evaporate in the hair, causing the hair to be dry and fragile and easy to break. 4) Photodamage and natural aging: Cystine, tyrosine and tryptophan in hair keratin caused by ultraviolet light in natural light The photodegradation of the group causes damage to the hair.
  • Ejiao sweet and flat, return to the lungs, liver, kidney.
  • Ejiao Gan, tonic blood "Ejiao is the length of blood, supplements the blood of the five internal organs, and nourishes the yin of the five internal organs, and is used for blood deficiency. The blood is full and the hair is nourished and moisturized.
  • the innovation of the invention is to use gelatin to nourish and nourish and moisturize the skin and hair, and to apply the gelatin or gelatin deep processing material in the preparation of the improved hair composition.
  • the improved hair quality is reflected in the following two aspects: 1) improving the smoothness, brightness and hair growth of normal hair; 2) repairing due to physical factors (such as straightening), chemical factors (such as hair dyeing, bleaching) and heating Hair damage caused by (such as perm).
  • physical factors such as straightening
  • chemical factors such as hair dyeing, bleaching
  • heating Hair damage caused by such as perm.
  • One of the objects of the present invention is to provide an application of a gelatin or gelatin deep processing material in the preparation of a composition for improving hair quality, particularly in the preparation of a composition for treating the following diseases and improving the following symptoms:
  • the improved hair quality includes: 1) improving the smoothness, brightness and hair growth of normal hair; 2) repairing hair damage caused by physical factors, chemical factors and heating.
  • the hair damage according to the present invention refers to dryness, breakage, rough feeling and glossiness caused by physical and chemical changes such as a decrease in water content of the hair caused by natural or human factors, loss of protein degradation, and the like.
  • a second object of the present invention is to provide an application of a gelatin or gelatin deep processing material in the preparation of a hair growth or a composition for increasing the number of hair follicles.
  • the gelatin of the present invention is an gelatin which can be purchased directly from the market or prepared according to the prior art and which meets the medicinal standards or health food standards or food standards.
  • the gelatin is prepared by the following steps: dicing the simmered skin into a steaming machine, and first adding 1.5 times the weight of the rind After heating, the temperature in the steaming machine is between 117 ° C and 119 ° C. After 120 minutes, the glue is discharged, and the peeling is repeated three times. The juice after three times of peeling is filtered, centrifuged, and evaporated. The evaporated glue is placed in a sandwich pot and further concentrated (can be added with appropriate amount of rice wine, rock sugar and soybean oil) to a thick paste, condensed, diced, and dried to obtain.
  • the Ejiao deep processing material refers to a single substance or a plurality of single substances of amino acids, oligopeptides, polypeptides, proteins having a molecular weight of 100 to 350,000 Da obtained by degradation of Ejiao, and further comprising a chemical substance from the above single substance. A mixture of new and new substances obtained after modification.
  • the Ejiao deep processing material is prepared by the following steps: dicing the husk after the immersion treatment into a steaming machine, and adding the weight of the suede for the first time is 1.5.
  • the water is doubled, heated to a temperature between 117 ° C and 119 ° C in the steaming machine. After 120 minutes, the glue is discharged, and the skin is repeated three times.
  • the juice after three times of peeling is filtered, centrifuged, and evaporated.
  • the evaporated glue is placed in a sandwich pot and further concentrated to a gel form for use; the gelatin glue is taken, the pH is adjusted to 1.0-3.0, and pepsin is added at a temperature of 36-42 ° C for enzymatic hydrolysis, inactivation, and pH adjustment. 7.5-8.5 adding trypsin to enzymatic hydrolysis at 36-42 ° C, inactivation, and then inactivated enzymatic hydrolysate and then ultrafiltration with 5KD ultrafiltration column to obtain ultrafiltrate, low temperature concentration, drying, that is .
  • the final concentration of pepsin (3000 U/mg) added is 0.1-0.8% (w/w)
  • the final concentration of trypsin (250 U/mg) added is 0.1-0.8%. (w/w).
  • the composition refers to a composition prepared from an Ejiao or Ejiao deep processing material or an Ejiao or Ejiao deep processing material and at least one of the following forms.
  • the natural product refers to a constituent of an animal, a plant, an insect, a marine organism, and a microorganism or a metabolite thereof, and a plurality of endogenous chemical components in humans and animals, including but not limited to the following substances; : proteins, peptides, amino acids, nucleic acids, various enzymes, monosaccharides, oligosaccharides, polysaccharides, glycoproteins, resins, colloids, lignin, vitamins, fats, oils, waxes, alkaloids, volatile oils, flavonoids, glycosides Naturally occurring chemical constituents such as terpenoids, phenylpropanoids, organic acids, phenols, terpenes, lactones, steroids, phthalic acids, and antibiotics.
  • proteins, peptides, amino acids, nucleic acids various enzymes, monosaccharides, oligosaccharides, polysaccharides, glycoproteins, resins, colloids, lignin, vitamins, fats
  • compositions of the present invention may be in any pharmaceutical, food or cosmetic dosage form including, but not limited to, the following dosage forms: tablets, sugar-coated tablets, film-coated tablets, enteric coated tablets, capsules, Hard capsule, soft capsule, oral liquid, buccal, granule, granule, pill, powder, ointment, dan, suspension, powder, solution, injection, suppository, ointment, plaster, cream , sprays, drops, patches, tinctures.
  • the present invention provides a new medical application of Ejiao and opens up new application fields thereof. Specifically, the present invention provides an application of Ejiao or Ejiao deep processing materials in preparing a composition for improving hair quality, preparing hair growth, and increasing the number of hair follicles. .
  • Ejiao has a significant nourishing effect on hair, mainly as follows: Ejiao can increase the number and type of white blood cells in the anemia model induced by cyclophosphamide; the determination of amino acid content shows that Ejiao has the effect of increasing the amino acid content in animal hair; The growth length and the number of hair follicles showed that Ejiao has the effect of promoting hair growth and increasing the number of hair follicles.
  • Ejiao raw materials from the ingredients, safe to take, have a long history of use, suitable for patients of different ages need to improve hair quality.
  • Pharmacological tests and human tests have confirmed that the composition prepared from the Ejiao or Ejiao deep processing materials can significantly improve the amino acid content in the hair, repair the damaged scales, improve the softness of the hair and the surface gloss, thereby achieving the purpose of improving hair quality.
  • 1a-1d are photographs of hair growth of the Ejiao test group at a high dose of 0d, 4d, 20d and a low dose of 20d, respectively.
  • 2a-2c are photographs of hair growth of the model control group of the present invention at 0d, 4d, and 20d, respectively.
  • 3a-3c are photographs of hair growth of the negative control group of the present invention at 0d, 4d, and 20d, respectively.
  • 4a-4e are photographs of pathological examination results of mouse hair follicles in the high, medium and low dose groups of the Ejiao test of the present invention, the model group and the control group, respectively.
  • Fig. 5 is an electron microscopic comparison of the hair scale changes of the blank group, the edible group 1 and the edible group 2 by electron microscopy ( ⁇ 2000).
  • composition prepared by the Ejiao or Ejiao deep processing material of the present invention on improving hair quality is further confirmed by the following examples.
  • the immersed treated rind is cut into pieces and placed in a steaming machine.
  • the first time the weight of the mash is 1.5 times of water, and the temperature in the steaming machine is heated to between 117 ° C and 119 ° C for 120 minutes.
  • the glue was discharged, and the skin was repeated three times.
  • the juice after three times of skin peeling was filtered, centrifuged, and evaporated. After evaporating, the glue is placed in a sandwich pot and further concentrated (can be added with appropriate amount of rice wine, rock sugar and soybean oil) to a thick paste, condensed, diced, and dried to obtain.
  • the immersed treated rind is cut into pieces and placed in a steaming machine.
  • the first time the weight of the mash is 1.5 times of water, and the temperature in the steaming machine is heated to between 117 ° C and 119 ° C for 120 minutes.
  • the glue was discharged, and the skin was repeated three times.
  • the juice after three times of skin peeling was filtered, centrifuged, and evaporated.
  • the glue is placed in a sandwich pot and further concentrated to a gelatinous state for use; the gelatin glue is taken, and the pH is adjusted to 2 by adding pepsin (3000 U/mg) to a final concentration of 0.5% (w/w) at 42.
  • the living enzymatic hydrolysate is then ultrafiltered with a 3KD ultrafiltration column to obtain an ultrafiltrate, concentrated at a low temperature, and dried to obtain an Ejiao deep processing material.
  • the immersed treated rind is cut into pieces and placed in a steaming machine.
  • the first time the weight of the mash is 1.5 times of water, and the temperature in the steaming machine is heated to between 117 ° C and 119 ° C for 120 minutes.
  • the glue was discharged, and the skin was repeated three times.
  • the juice after three times of skin peeling was filtered, centrifuged, and evaporated.
  • the glue is placed in a sandwich pot and further concentrated to a gelatinous state for use; the gelatin glue is taken, and the pH is adjusted to 2.5 to add pepsin (3000 U/mg) to a final concentration of 0.8% (w/w).
  • Enzymatic hydrolysis at 40 ° C, inactivation adjust the pH to 7.5 and add trypsin (250 U / mg) to a final concentration of 0.2% (w / w), enzymatic hydrolysis at 40 ° C, inactivated, and then The inactivated enzymatic hydrolysate is then subjected to ultrafiltration using a 5 KD ultrafiltration column to obtain an ultrafiltrate, concentrated at a low temperature, and dried to obtain an Ejiao deep processing material.
  • Reagent preparation After preparing the powder of Dong'e Ejiao, it is dissolved in an appropriate amount of distilled water to prepare a solution with a dose of 135 mg/mL, 67.5 mg/mL, and 33.75 mg/mL, which are respectively labeled as high, medium and low dose solutions.
  • mice After depilation for 24h, 75 hair removal areas were smooth and skin-injured mice were randomly divided into 5 groups, which were recorded as high, medium and low dose groups, negative control and model control group, 15 rats/group.
  • Ejiao test group and model control group one-time intraperitoneal injection of cyclophosphamide at a dose of 250mg/100g ⁇ bw, the dosage is 0.2mL/10g ⁇ bw; negative control group, according to 0.2mL/10g ⁇ bw Amount of administration
  • a test model was established by intraperitoneal injection of physiological saline.
  • Each test group was orally administered with a corresponding dose of Ejiao solution, and the daily gavage volume was 0.2 mL/10 g ⁇ bw; the negative control group and the model control group were orally administered with distilled water, and the daily gavage volume was 0.2 mL/ 10g ⁇ bw. Each group was administered continuously for 20 days.
  • mice After pretreatment of C57BL/6 mice for 24 hours, 75 groups of smooth and skinless mice with hair loss were selected and a mouse anemia model was established and administered by gavage, as described in Section 2.5.
  • the skin tissues of the blood and hair removal areas of each group of mice were collected at 4d, 12d, and 20d, respectively, and hematological and histopathological examinations were performed.
  • hair samples of each group of mice were collected, observed by electron microscopy, and the amino acid content of remaining newborn hair of each group of animals was examined.
  • Hematology items white blood cells, red blood cells, hemoglobin, hematocrit, platelets.
  • mice The statistical results of the hematological index test results of the mice showed that the white blood cells and their classification numbers in the experimental group and the negative control group were larger than the model control. There were significant and extremely significant differences between the dose groups (*P ⁇ 0.05, **P ⁇ 0.01). The results are shown in Table 1, Table 2 and Table 3.
  • test results are expressed as mean ⁇ standard deviation. *P ⁇ 0.05, **P ⁇ 0.01
  • test results are expressed as mean ⁇ standard deviation. *P ⁇ 0.05, **P ⁇ 0.01
  • test results are expressed as mean ⁇ standard deviation. *P ⁇ 0.05, **P ⁇ 0.01
  • test results are expressed as mean ⁇ standard deviation (*P ⁇ 0.05, **P ⁇ 0.01)
  • the results of electron microscopy showed that there was a bamboo-like change in the newborn hair of the model control animals, and the hair growth of the negative control group was normal.
  • the results of the animals in the test group showed differences between the groups.
  • the hair diameter difference between the groups was obvious. The growth was good.
  • the high-dose group of hair between the test groups was significantly larger than the middle and low dose groups.
  • the hair diameter of the test group was significantly larger than that of the model control.
  • the animal hair growth was significantly different between the groups.
  • the skin of the test group and the model control animals turned black at 4 days, the skin of the negative control group was still pink at 4 days, and the high dose group of the test group for 20 days.
  • the hair density was significantly better than the low dose group and the control group, but not the negative control group.
  • Ejiao can increase the number and type of white blood cells in the anemia model of mice induced by cyclophosphamide; the determination of amino acid content shows that it has the effect of increasing the amino acid content in animal hair; the length of hair growth and the number of hair follicles show that it promotes hair growth and Increase the number of hair follicles.
  • Ejiao can promote hair growth and improve hair quality in anemia mice through a combination of various effects.
  • Test Example 2 Human test test
  • Dong'e Ejiao was supplied by Shandong Dong'e Ejiao Co., Ltd., batch number: 1211037; Ejiao deep processing material sample was prepared according to the method of Example 2, batch number: 1312043.
  • the changes of hair scales were observed by electron microscopy.
  • the results of hair electron microscope comparison ( ⁇ 2000) showed that the diameter of hair in the blank control group was relatively small.
  • the diameter of head hair in group 1 and group 2 was significantly larger than that in blank group, and the hair scales were evenly distributed. It shows that Ejiao and Ejiao deep processing materials can improve hair quality.
  • the edges of the bamboo-like hair scales were lifted up and even ruptured, and the surface of the hair became rough and tarnished.
  • the distribution of hair scales in the edible group 1 and 2 was even, indicating that the gelatin and gelatin deep-processing materials can make the hair smooth and shiny. 5 is shown.
  • N is the number of measurements (10 times)
  • the static friction coefficient and the dynamic friction coefficient of the hair were measured on a Y151 type fiber friction meter, and the results are shown in Table 7 below.
  • the tension clamp has a mass of 200 mg and a dynamic friction speed of 30 r/min.
  • the chemical properties of hair protein are inactive and stable, but it is still sensitive to heat, acid, alkali, etc. In addition, it will also be stretched and deformed under the action of mechanical force. Hair is damaged and destroyed in the process of combing and washing, especially in perm and hairdressing. The disulfide bond in the hair is easily reduced by the mercapto compound (the main component of the chemical cold agent), and the molecular structure of the hair surface is affected. To the destruction, the hair is deteriorated, dry and easy to fork, and the elasticity and strength of the hair are also reduced, becoming fragile and fragile.
  • the surface static properties (Us) and dynamic friction coefficient (Ua) are often used to measure the surface properties of an object or material.
  • the quality of hair depends on the integrity of the hair structure and components. Damage to hair caused by various environmental and physicochemical factors is mainly caused by damage to hair structure and components.
  • capillary electrochemical detection technology was used to evaluate the degree of head luminescence damage by monitoring changes in the content of cysteine and tyrosine in hair before and after hot dyeing.
  • the content of cysteine and tyrosine in the hair after heat dyeing was reduced to some extent, but the cysteine and tyrosine in the hair were used in the group after taking the gelatin or gelatin deep processing material. The content is basically restored to the level before the hot dyeing.
  • Example 1 Female, 28 years old, with yellow hair and partial bifurcation. After taking Ejiao for 1 month, the hair quality is obviously improved, and the bifurcation phenomenon disappears. After the hot dyeing treatment, the gelatin is continued, and the hair quality is obviously obtained. Improved, hair quality returned to the level before hot dyeing.
  • Example 2 Female, 23 years old, hair loss is severe, and part of the fork is dull, hair is sparse and oily. The hair must be washed once a day. After taking the gelatin deep processing material of Example 2 for 1 month, the hair quality is obviously improved. The bifurcation disappeared, the hair could be washed for 3 days, and the hair loss phenomenon was significantly improved after each shampooing, and the hair was thicker than before; after the hot dyeing treatment, the gelatin deep processing material of Example 2 was continued. The quality was significantly improved and the hair quality returned to the level before hot dyeing.

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Abstract

阿胶或阿胶深加工物质在制备改善发质组合物中的应用。

Description

阿胶或阿胶深加工物质在制备改善发质的组合物中的应用
相关申请案的交叉参考
本申请案主张2013年9月25日提出的，申请号为201310441560.6的中国临时专利申请案的优先权，所述申请案的说明书以全文引用的方式并入本文中。
技术领域
本发明涉及阿胶或阿胶深加工类产品的新用途，特别涉及阿胶或阿胶深加工物质在制备改善发质的组合物中的应用。
背景技术
头发损伤可依造成因素的不同分以下几种类型：1)物理损伤：日常梳理头发、拉直头发的牵拉力及摩擦力引起头发表层覆盖的毛小皮鳞片的起翘及脱落；2)化学损伤：烫发剂、染发剂、漂白剂等物质破坏头发油脂层，穿透毛小皮鳞片进入毛皮质引起角蛋白二硫键断裂，造成头发疏水性、强度和弹性的下降；3)热损伤：热吹风或电热烫发使得头发中水分蒸发导致头发干燥脆弱、易断裂；4)光损伤及自然老化：自然光中的紫外光照射引起的头发角蛋白中胱氨酸、酪氨酸和色氨酸等基团的光降解，进而导致头发受损老化。
阿胶，性味甘、平，归肺、肝、肾经。《本草纲目》：“阿胶，大要只是补血与液，故能清肺益阴而治诸证......阿胶之甘，以补阴血......”。阿胶为补血之长，补五脏之血，滋五脏之阴，用于血虚诸症。血液充盈，毛发方得滋养润泽。本发明的创新之处就是运用阿胶补血、滋养润泽肌肤毛发的作用，在制备改善发质组合物中应用阿胶或阿胶深加工物质。所述的改善发质体现在以下两方面：1)改善正常毛发的光滑度、光亮度及促进毛发生长；2)修复因物理因素(如拉直)、化学因素(如染发、漂白)及加热(如烫发)引起的发质损伤。阿胶或阿胶深加工物质在制备改善发质的组合物中的应用还未见有报道。
发明内容
本发明的目的之一在于提供阿胶或阿胶深加工物质在制备改善发质的组合物中的应用，特别是在制备治疗以下疾病、改善以下症状的组合物中的应用：
所述改善发质包括：1)改善正常毛发的光滑度、光亮度及促进毛发生长；2)修复因物理因素、化学因素及加热引起的发质损伤。
本发明所述的发质损伤是指自然或人为因素造成的毛发的含水量下降、蛋白质降解丢失等物理化学变化引起的干枯、易断裂、手感粗糙及光泽度下降。
本发明的目的之二在于提供阿胶或阿胶深加工物质在制备生发或提升毛囊数量的组合物中的应用。
本发明所述的阿胶是可以从市场直接购买得到或根据现有技术制备且符合药用标准或保健食品标准或食品标准的阿胶。
在本发明的一个具体实施例中，所述的阿胶是通过以下步骤制备得到的：将浸泡处理后的驴皮切块，置蒸汽化皮机内，第一次加驴皮重量1.5倍的水，加热使蒸汽化皮机内温度达117℃-119℃之间，保持120分钟后放出胶汁，重复化皮3次，将三次化皮后的胶汁过滤、离心后蒸发。将蒸发后的胶液置夹层锅内继续浓缩(可分别加适量黄酒、冰糖及豆油)至稠膏状，冷凝，切块，晾干，即得。
本发明中，所述的阿胶深加工物质是指由阿胶降解得到的分子量在100～350000Da的氨基酸、寡肽、多肽、蛋白质的单一物质或多种单一物质的混合物，还包括由以上单一物质经化学修饰后得到的新物质及新物质的混合物。
在本发明的一个具体实施例中，所述的阿胶深加工物质，是通过以下步骤制备得到的：将浸泡处理后的驴皮切块，置蒸汽化皮机内，第一次加驴皮重量1.5倍的水，加热使蒸汽化皮机内温度达117℃-119℃之间，保持120分钟后放出胶汁，重复化皮3次，将三次化皮后的胶汁过滤、离心后蒸发。将蒸发后的胶液置夹层锅内继续浓缩至胶浆状，备用；取阿胶胶浆，调pH至1.0-3.0加入胃蛋白酶在36-42℃温度下进行酶解，灭活，调pH至7.5-8.5加入胰蛋白酶在36-42℃温度下进行酶解，灭活，然后将灭活的酶解液继而用5KD超滤柱进行超滤，得超滤液、低温浓缩，干燥，即得。
在本发明中，优选的，所加入的胃蛋白酶(3000U/mg)的终浓度为0.1-0.8％(w/w)，所加入的胰蛋白酶(250U/mg)的终浓度为0.1-0.8％(w/w)。
在本发明中，所述的组合物是指由阿胶或阿胶深加工物质或者阿胶或阿胶深加工物质与以下至少一种形式的物质制备而成的组合物。
1)一种或多种中药材；
2)一种或多种天然产物；
3)一种或多种化合物；
4)一种或多种药用辅料；
5)一种或多种食品添加剂；
6)一种或多种化妆品添加剂；
其中，所述的天然产物是指动物、植物、昆虫、海洋生物和微生物体内的组成成分或其代谢产物以及人和动物体内许许多多内源性的化学成分的统称，包括但不限于以下物质：蛋白质、多肽、氨基酸、核酸、各种酶类、单糖、寡糖、多糖、糖蛋白、树脂、胶体物、木质素、维生素、脂肪、油脂、蜡、生物碱、挥发油、黄酮、糖苷类、萜类、苯丙素类、有机酸、酚类、醌类、内酯、甾体化合物、鞣酸类、抗生素类等天然存在的化学成分。
本发明所述的组合物可以是任何的药用、食品用或化妆品剂型，这些剂型包括但不限于以下剂型：片剂、糖衣片剂、薄膜衣片剂、肠溶衣片剂、胶囊剂、硬胶囊剂、软胶囊剂、口服液、口含剂、颗粒剂、冲剂、丸剂、散剂、膏剂、丹剂、混悬剂、粉剂、溶液剂、注射剂、栓剂、软膏剂、硬膏剂、霜剂、喷雾剂、滴剂、贴剂、搽剂。
本发明的优点在于：
1、本发明提供了阿胶新的医疗用途，开拓了其新的应用领域；具体的，本发明提出了阿胶或阿胶深加工物质在制备改善发质、制备生发、提升毛囊数量的组合物中的应用。
2、阿胶对毛发的滋养作用明显，主要表现为：阿胶可以增加环磷酞胺致小鼠贫血模型体内的白细胞数量和种类；氨基酸含量测定结果显示阿胶有提高动物毛发中氨基酸含量的作用；毛发生长长度及毛囊数量结果显示阿胶有促进毛发生长及提升毛囊数量的作用。
3、阿胶原料来源于食材，服用安全，使用历史悠久，适合于不同年龄阶段的需要改善发质的患者服用。经药理试验和人体试验证实，由阿胶或阿胶深加工物质制备成的组合物可显著提高毛发中的氨基酸含量、修复损伤毛鳞片、改善头发柔软性及表面光泽等，从而达到改善发质的目的。
附图说明
下面结合附图对本发明作进一步的说明。
图1a-图1d分别为本发明阿胶试验组在0d，4d，20d高剂量，20d低剂量的毛发生长照片。
图2a-图2c分别为本发明模型对照组在0d，4d，20d的毛发生长照片。
图3a-图3c分别为本发明阴性对照组在0d，4d，20d的毛发生长照片。
图4a-图4e分别为本发明阿胶试验高、中、低剂量组，模型组和对照组的小鼠毛囊病理检查结果照片。
图5为电镜扫描法观察空白组、食用组1以及食用组2的头发毛鳞片变化的电镜对比图(×2000)。
具体实施方式
本发明所述的由阿胶或阿胶深加工物质制备成的组合物对改善发质所产生的积极作用通过以下实施例进一步证实.
以下实施例仅是范例性的，并不对本发明的范围构成任何限制。
实施例1：阿胶的制备
将浸泡处理后的驴皮切块，置蒸汽化皮机内，第一次加驴皮重量1.5倍的水，加热使蒸汽化皮机内温度达117℃-119℃之间，保持120分钟后放出胶汁，重复化皮3次，将三次化皮后的胶汁过滤、离心后蒸发。将蒸发后胶液置夹层锅内继续浓缩(可分别加适量黄酒、冰糖及豆油)至稠膏状，冷凝，切块，晾干，即得。
实施例2：阿胶深加工物质的制备
将浸泡处理后的驴皮切块，置蒸汽化皮机内，第一次加驴皮重量1.5倍的水，加热使蒸汽化皮机内温度达117℃-119℃之间，保持120分钟后放出胶汁，重复化皮3次，将三次化皮后的胶汁过滤、离心后蒸发。将蒸发后胶液置夹层锅内继续浓缩至胶浆状，备用；取阿胶胶浆，调pH至2加入胃蛋白酶(3000U/mg)，使其终浓度达到0.5％(w/w)在42℃温度下进行酶解，灭活，调pH至8.0加入胰蛋白酶(250U/mg)，使其终浓度达到0.5％(w/w)在42℃温度下进行酶解，灭活，然后将灭活的酶解液继而用3KD超滤柱进行超滤，得超滤液、低温浓缩，干燥，即得阿胶深加工物质。
实施例3：阿胶深加工物质的制备
将浸泡处理后的驴皮切块，置蒸汽化皮机内，第一次加驴皮重量1.5倍的水，加热使蒸汽化皮机内温度达117℃-119℃之间，保持120分钟后放出胶汁，重复化皮3次，将三次化皮后的胶汁过滤、离心后蒸发。将蒸发后胶液置夹层锅内继续浓缩至胶浆状，备用；取阿胶胶浆，调pH至2.5加入胃蛋白酶(3000U/mg)，使其终浓度达到0.8％(w/w)，在40℃温度下进行酶解，灭活，调pH至7.5加入胰蛋白酶(250U/mg)，使其终浓度达到0.2％(w/w)，在40℃温度下进行酶解，灭活，然后将灭活的酶解液继而用5KD超滤柱进行超滤，得超滤液、低温浓缩，干燥，即得阿胶深加工物质。
试验例1：药理实验
1材料与动物
1.1材料：东阿阿胶(山东东阿阿胶股份有限公司提供，制备方法与实施例1方法相同，批号：1211037)；注射用环磷酰胺(山西普德药业股份有限公司提供，批号：04110603)；松香、石蜡和生理盐水(山东齐都药业有限公司提供，批号：2011112603)。
1.2实验动物：120只SPF级C57BL/6雌性小鼠，15～20g(北京华阜康生物科技股份有限公司提供，生产许可证号：SCXK(京)2009-0004)；小鼠饲料(北京华阜康生物科技股份有限公司提供，生产许可证号：SCXK(京)2009-0008)。
1.3环境条件：山东省实验动物中心屏障环境动物室，使用许可证号：SYXK(鲁)20090014，室温20～25℃，相对湿度50～70％。
2方法
2.1试剂配制：将东阿阿胶制成粉末后，用适量蒸馏水溶解，配制成剂量为135mg/mL，67.5mg/mL，33.75mg/mL的溶液，分别标记为高、中、低剂量溶液。
2.2实验动物预处理：将松香和石蜡按1∶1比例混合溶解，涂抹至小鼠背部皮肤(2×3cm2)，待其凝固后拔除涂抹区域皮肤表面的毛发。
2.3试验分组：经脱毛24h后，将75只脱毛区域光滑无皮肤破损小鼠随机分为5组，分别记为高、中、低剂量组，阴性对照和模型对照组，15只/组。
2.4建立模型：阿胶试验组和模型对照组，按250mg/100g·bw的剂量一次性腹腔注射环磷酰胺，给药量为0.2mL/10g·bw；阴性对照组，按0.2mL/10g·bw给药量 一次性腹腔注射生理盐水，建立试验模型。
2.5给药：各试验组经口灌胃对应剂量的阿胶溶液，每日灌胃量0.2mL/10g·bw；阴性对照组和模型对照组经口灌胃蒸馏水，每日灌胃量0.2mL/10g·bw。各组均连续给药20d。
2.6试验步骤：对C57BL/6小鼠进行预处理24h后，挑选75只脱毛区域光滑无皮肤破损小鼠分组，建立小鼠贫血模型，灌胃给药，如2.5节中所述。分别在给药4d、12d、20d时，采集各组小鼠血液和脱毛区域的皮肤组织，进行血液学检测和组织病理学检查。在给药后20d，收集各组小鼠的毛发样本，借助电子显微镜进行形态学观察，并检测各组动物剩余新生毛发的氨基酸含量。
3结果
3.1血液学项目：白细胞、红细胞、血红蛋白、红细胞压积、血小板。
3.2毛发检测指标：长度、形态、氨基酸。
3.3组织病理检查：皮肤完整性，充血、水肿、炎细胞浸润程度；进行毛囊计数并统计。
3.4血液学指标检查结果
小鼠血液学指标检查结果统计表显示，试验组及阴性对照组白细胞及其分类数量大于模型对照。各剂量组间存在显著及极显著差异(*P＜0.05，**P＜0.01)。结果见表1，表2和表3。
表1  小鼠血液学指标检查结果(4d)
Figure PCTCN2014000868-appb-000001
注：检测结果以均数±标准差表示。*P＜0.05，**P＜0.01
表2  小鼠血液学指标检查结果(12d)
Figure PCTCN2014000868-appb-000002
Figure PCTCN2014000868-appb-000003
注：检测结果以均数±标准差表示。*P＜0.05，**P＜0.01
表3  小鼠血液学指标检查结果(20d)
Figure PCTCN2014000868-appb-000004
注：检测结果以均数±标准差表示。*P＜0.05，**P＜0.01
3.5毛发中氨基酸含量测定
从表4中可以看出，高、中剂量组动物毛发中氨基酸含量数值均大于模型对照。
表4  氨基酸含量测定结果
Figure PCTCN2014000868-appb-000005
Figure PCTCN2014000868-appb-000006
3.6小鼠毛发生长状况
从小鼠毛发长度统计结果(结果见表5)和毛发生长照片(见图1-图3)中可以看出，20d时处死小鼠的毛发长度及浓密程度均优于模型对照但不及阴性对照组。试验组与阴性对照组动物毛发长度无显著差异(P＞0.05)，模型对照与阴性对照组动物毛发长度差异极显著(P＜0.01)。
表5  小鼠毛发长度统计结果(20d)
Figure PCTCN2014000868-appb-000007
注：检测结果以均数±标准差表示(*P＜0.05，**P＜0.01)
3.7电镜结果
电镜观察结果显示，模型对照动物新生毛发出现竹节样改变，阴性对照组动物毛发生长情况正常，试验组动物给药后的结果出现组间差异，各组间毛发直径差异明显，阴性对照组毛发生长情况良好，试验组间毛发直径高剂量组明显大于中、低剂量组，试验组毛发直径明显大于模型对照。
3.8病理检查结果
从表6和图4中可以看出，各剂量组动物病理观察未见充血、水肿及炎细胞浸润。试验组动物毛囊数量统计结果大于模型对照但小于阴性对照组。试验组动物毛囊数量与阴性对照组动物毛囊数量差异显著(P＜0.05)，模型对照动物毛囊数量与阴性对照组动物毛囊数量差异极显著(P＜0.01)。
表6  小鼠皮肤病理检查及毛囊数量统计结果
Figure PCTCN2014000868-appb-000008
Figure PCTCN2014000868-appb-000009
注：毛囊数量检测结果以均数±标准差表示。*P＜0.05，**P＜0.01
4结论
试验过程中，动物毛发生长情况在各组之间出现明显差异，试验组及模型对照动物皮肤在4d时变黑，阴性对照组动物于4d时皮肤颜色仍为粉色，试验组中高剂量组动物20d时毛发浓密程度明显优于低剂量组及对照组，但不及阴性对照组。
上述试验表明：阿胶可以增加环磷酰胺致小鼠贫血模型体内的白细胞数量和种类；氨基酸含量测定结果显示有提高动物毛发中氨基酸含量的作用；毛发生长长度及毛囊数量结果显示有促进毛发生长及提升毛囊数量的作用。
综上，通过整体试验结果分析，阿胶可以通过多方面综合作用，促进贫血小鼠的毛发生长及改善毛发质量的作用。
试验例2：人体试服试验
1材料与人员
1.1材料：东阿阿胶由山东东阿阿胶股份有限公司提供，批号：1211037；阿胶深加工物质样品按照实施例2的方法制备得到，批号：1312043。
1.2实验人员：全部人员共30个，其中男9例，女27例，平均年龄为23.6岁，近一年内头发没有进行过烫染等物理或化学处理。将其随机分为空白组、食用组1和食用组2。三组一般资料比较无统计学差异，具有可比性。
2方法：将三组人员，实验前留取头发样1；将三组人员进行相同的烫染处理后，分别留取头发样2；然后，食用组1一个月内每日口服服用阿胶，每日9克，食用组2一个月内每日口服服用实施例2的阿胶深加工物质样品，每日6克，空白组不服用任何药物；一月后三组人员留取头发样3；试验期间，不得使用任何修复或护理头发的产品。头发试样的处理：收集的头发，混合均匀，用十二烷基硫酸钠溶液洗涤后，漂洗干净，自然晾干待用。
3结果与分析
3.1对受损头发毛鳞片的修复作用
电镜扫描法观察头发毛鳞片的变化，头发电镜对比图(×2000)结果显示：空白对照组头发直径比较细小；而食用组1、2组头毛发直径明显大于空白组，且毛鳞片分布均匀，表明阿胶及阿胶深加工物质可改善头发质量。空白组头发出现竹节样毛鳞片边缘翘起，甚至破裂，头发表面变得粗糙、失去光泽；食用组1、2头发鳞片分布均匀，表明阿胶及阿胶深加工物质可使头发柔滑，有光泽，图5所示。
3.2头发弹性和摩擦系数测定
3.2.1头发的弹性实验
取10根头发试样，在Y391型纱线弹性仪上测其弹性。测定条件：牵引力为199g，预加张力为2.5g，试样长度为50mm。取试样长度的10％为定伸长值(L1)，据测得的残留伸长值(Li)，计算头发的定伸长弹性率R(％)，食用阿胶前后对头发弹性的影响：
Figure PCTCN2014000868-appb-000010
式中：N为测定次数(10次)
3.2.2头发的摩擦性实验
在Y151型纤维摩擦仪上测定头发的静摩擦系数和动摩擦系数，结果如下表7所示。张力钳质量为200mg，动摩擦转速为30r/min。
表7  空白组、食用组1、2头发的弹性和摩擦系数结果表
Figure PCTCN2014000868-appb-000011
结果分析：头发蛋白的化学性质不活泼，较稳定，但它对热、酸、碱等还是比较灵敏；另外，在机械力的作用下也将拉伸变形。头发在梳理和洗涤尤其是在烫发和美发的过程中，会受不同程度的损伤和破坏，头发中的二硫键很容易被巯基化合物(化学冷烫剂的主要成分)还原，头发表面分子结构遭到破坏，引起头发光泽变差，干枯且易分叉，同时头发的弹性和强度也降低，变得脆弱易断。另外，衡量一个物体或材料的表面性质常采用其表面静摩擦系数(Us)和动摩擦系数(Ua)。如果Us和 Ua较小，并且两者的差值也小，则这个物体表面就比较光滑，手感柔软，光泽也较好。因此，食用阿胶或阿胶深加工物质后头发的Us和Ua比未食用的头发降低较多，它们的差值(Us-Ua)也更小，即改善头发柔软性及表面光泽等效果明显。因而，头发变得比较柔软、光滑，手感较好。同时，光滑的头发表面对光的反射增强，增加了头发光泽。
3.3头发中半胱氨酸和酪氨酸的含量变化
根据文献“钱蕙，曹蕊，曹玉华.毛细管电化学检测法测定光损伤头发中的氨基酸[J].苏州科技学院学报，2008，25(2)：40-43.”进行了试验头发试样中半胱氨酸和酪氨酸的测定，具体试验结果见下表8。
表8  空白组、食用组1、2头发中半胱氨酸和酪氨酸含量结果表
Figure PCTCN2014000868-appb-000012
结果分析：头发发质的好坏取决于头发结构和组分的完整程度。头发受到各种环境和物理化学因素的影响而导致的损伤主要是头发结构和组分受到破坏。本实验采用毛细管电化学检测技术，通过监测烫染前后头发中半胱氨酸及酪氨酸的含量变化来评价头发光损伤的程度。本试验在烫染后头发中的半胱氨酸及酪氨酸的含量都有不同程度的降低，但使用组在服用阿胶或阿胶深加工物质后，头发中的半胱氨酸及酪氨酸的含量基本恢复到烫染前的水平。
3.4头发吸附铜离子的量表征头发的受损程度
参照文献“程若男，用铜离子吸附量评价头发受损程度，日用化学工业，2005，35(6)：400-402.”建立铜离子吸附法，通过测定头发吸附铜离子的量表征头发的受损程度，结果如下表9所示。
表9  空白组、食用组1、2的头发吸附铜离子量结果表
Figure PCTCN2014000868-appb-000013
Figure PCTCN2014000868-appb-000014
结果分析：当头发受到物理或化学损伤时，头发中角朊分子间的二硫键被切断，从而使头发带负电荷，这种带负电荷的头发浸在0.2mol/L的硫酸铜溶液中，会吸附铜离子，头发受损程度越大，所带负电荷越多，吸附的铜离子就越多，所以可以通过测定头发吸附铜离子的量来评价头发的受损程度。通过本试验结果可知，食用组1和食用2在烫染后分别食用阿胶或阿胶深加工物质样品都能改善发质，且基本都能恢复到烫染前的水平。
3.5典型食用者举例
例1：女，28岁，头发枯黄且部分分叉无光泽，再服用阿胶1个月后，发质明显改善，分叉现象消失；再进行烫染处理后，继续服用阿胶，发质明显得到改善，发质恢复为烫染前水平。
例2：女，23岁，头发脱发严重，且部分分叉无光泽，头发稀疏头油多，头发必须一天一洗，再服用实施例2的阿胶深加工物质1个月后，发质明显改善，分叉现象消失，头发可以3天一洗，且以前每次洗发时，掉头发的现象显著改善，头发比以前浓密；再进行烫染处理后，继续服用实施例2的阿胶深加工物质，发质明显得到改善，发质恢复为烫染前水平。

Claims (10)

  1. 阿胶或阿胶深加工物质在制备改善发质的组合物中的应用。
  2. 根据权利要求1所述的应用，其特征在于：所述的阿胶是通过以下方法制备得到的：将浸泡处理后的驴皮切块，置蒸汽化皮机内，第一次加驴皮重量1.5倍的水，加热使蒸汽化皮机内温度达117℃-119℃之间，保持120分钟后放出胶汁，重复化皮3次，将三次化皮后的胶汁过滤、离心后蒸发，将蒸发后胶液置夹层锅内继续浓缩至稠膏状，冷凝，切块，晾干，即得。
  3. 根据权利要求1所述的应用，其特征在于：所述的阿胶深加工物质是指由阿胶降解得到的分子量在100～350000Da的氨基酸、寡肽、多肽、蛋白质的单一物质或多种单一物质的混合物，还包括由以上单一物质经化学修饰后得到的新物质及新物质的混合物。
  4. 如权利要求3所述的应用，其特征在于所述的阿胶深加工物质是通过以下步骤制备得到的：将浸泡处理后的驴皮切块，置蒸汽化皮机内，第一次加驴皮重量1.5倍的水，加热使蒸汽化皮机内温度达117℃-119℃之间，保持120分钟后放出胶汁，重复化皮3次，将三次化皮后的胶汁过滤、离心后蒸发，将蒸发后胶液置夹层锅内继续浓缩至胶浆状，备用；取阿胶胶浆，调pH至1.0-3.0加入胃蛋白酶在36-42℃温度下进行酶解，灭活，调pH至7.5-8.5加入胰蛋白酶在36-42℃温度下进行酶解，灭活，然后将灭活的酶解液继而用3KD或5KD的超滤柱进行超滤，得超滤液、低温浓缩，干燥，即得。
  5. 根据权利要求1中所述的应用，其特征在于：所述改善发质包括：1)改善正常毛发的光滑度、光亮度及促进毛发生长；2)修复因物理因素、化学因素及加热引起的发质损伤。
  6. 根据权利要求1中所述的应用，其特征在于：所述组合物为由阿胶或阿胶深加工物质或者阿胶或阿胶深加工物质与以下至少一种形式的物质制备而成的组合物：
    1)一种或多种中药材；
    2)一种或多种天然产物；
    3)一种或多种化合物；
    4)一种或多种药用辅料；
    5)一种或多种食品添加剂；
    6)一种或多种化妆品添加剂；
    其中，所述的天然产物包括以下物质：蛋白质、多肽、氨基酸、核酸、各种酶类、单糖、寡糖、多糖、糖蛋白、树脂、胶体物、木质素、维生素、脂肪、油脂、蜡、生物碱、挥发油、黄酮、糖苷类、萜类、苯丙素类、有机酸、酚类、醌类、内酯、甾体化合物、鞣酸类、抗生素类等天然存在的化学成分。
  7. 根据权利要求1-6任一项中所述的应用，其特征在于：所述组合物按照制剂制备的常规方法制成各种剂型，包括：片剂、糖衣片剂、薄膜衣片剂、肠溶衣片剂、胶囊剂、硬胶囊剂、软胶囊剂、口服液、口含剂、颗粒剂、冲剂、丸剂、散剂、膏剂、丹剂、混悬剂、粉剂、溶液剂、注射剂、栓剂、软膏剂、硬膏剂、霜剂、喷雾剂、滴剂、贴剂、搽剂。
  8. 阿胶或阿胶深加工物质在制备生发或提升毛囊数量的组合物中的应用。
  9. 根据权利要求8所述的应用，其特征在于：所述的阿胶深加工物质是指由阿胶降解得到的分子量在100～350000Da的氨基酸、寡肽、多肽、蛋白质的单一物质或多种单一物质的混合物，还包括由以上单一物质经化学修饰后得到的新物质及新物质的混合物。
  10. 如权利要求9所述的应用，其特征在于所述的阿胶深加工物质是通过以下步骤制备得到的：将浸泡处理后的驴皮切块，置蒸汽化皮机内，第一次加驴皮重量1.5倍的水，加热使蒸汽化皮机内温度达117℃-119℃之间，保持120分钟后放出胶汁，重复化皮3次，将三次化皮后的胶汁过滤、离心后蒸发，将蒸发后胶液置夹层锅内继续浓缩至胶浆状，备用；取阿胶胶浆，调pH至1.0-3.0加入胃蛋白酶在36-42℃温度下进行酶解，灭活，调pH至7.5-8.5加入胰蛋白酶在36-42℃温度下进行酶解，灭活，然后将灭活的酶解液继而用3KD或5KD的超滤柱进行超滤，得超滤液、低温浓缩，干燥，即得。
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