CN111743800A

CN111743800A - Composition and preparation method and application thereof

Info

Publication number: CN111743800A
Application number: CN202010661385.1A
Authority: CN
Inventors: 陈强; 柴小华
Original assignee: Hangzhou Keteng Biological Product Co ltd
Current assignee: Hangzhou Keteng Biological Product Co ltd
Priority date: 2020-07-10
Filing date: 2020-07-10
Publication date: 2020-10-09
Also published as: WO2022007533A1

Abstract

The invention discloses a composition, a preparation method and application thereof. The composition contains acetyl hexapeptide-8 and pentapeptide-18. The composition can be used for removing wrinkles.

Description

Composition and preparation method and application thereof

Technical Field

The invention relates to the field of dermatology, in particular to a composition for removing wrinkles and a preparation method thereof.

Background

With the age, the skin and muscles of people gradually relax, and the face appearance gradually goes towards aging. Especially in the age range of 25-35 years, wrinkles may be caused by photoaging, habitual expression, skin water deficiency, irregular life, insufficient sleep, excessive weight loss, etc. When the nerve synaptic vesicle is fused to release acetylcholine, muscle cells begin to contract after receiving the acetylcholine, and repeated muscle contraction causes wrinkles. Synaptic vesicle fusion requires two key factors: stable SNARE complexes and calcium ion uptake are formed. The puzzlement of the expression lines is particularly obvious in female population, and the problem that the facial aging is effectively relieved, which is urgently needed to be solved in clinical plastic cosmetology for vast females.

Currently, the most main mode for removing expression lines is to inject botulinum toxin, but the botulinum toxin has side effects, and some injection reactions such as blood stasis, bleeding and the like can occur on the local part of the injection; secondly, some side effects caused by excessive injection amount or dispersion of the injected medicine include local ptosis, such as ptosis or local over-relaxation, or expression stagnation caused by local paralysis, so-called adverse reactions of injection, and also some expression or appearance asymmetry of two sides caused by asymmetric injection.

Therefore, there is a strong need in the art to provide a product and means for wrinkle removal that is convenient and effective, and has no side effects.

Disclosure of Invention

The present invention aims to provide a product capable of effectively removing wrinkles and a preparation method thereof.

In a first aspect of the invention, a composition is provided comprising acetyl hexapeptide-8 and pentapeptide-18.

In another embodiment, the mass ratio of pentapeptide-18 to acetyl hexapeptide-8 in the composition is 1:0.5 to 3.5.

In another embodiment, the composition further comprises a moisturizing component; the moisture-keeping component is selected from one or more than two of the following components: hyaluronic acid or a salt thereof, glycerol, collagen, and mucopolysaccharide.

In another embodiment, the composition further comprises a buffer which makes the pH of the composition to be a liquid or gel 6-7.6; the buffer is selected from phosphate, acetate, sodium formate, or barbiturate sodium.

The present invention provides a composition comprising:

in another embodiment, the composition further comprises a balance of water.

In a second aspect of the present invention, there is provided a process for the preparation of a composition provided by the present invention as described above, said process comprising the steps of: the solution containing acetyl hexapeptide-8 and pentapeptide-18 is mixed with the buffer and the moisturizing ingredient to obtain the composition provided by the present invention as described above.

In a third aspect of the invention, there is provided the use of a composition as provided herein, as described above, for removing wrinkles or for the preparation of a cosmetic or personal care product for removing wrinkles.

In another embodiment, the wrinkles include dynamic wrinkles and gravitational wrinkles.

In a fourth aspect of the present invention there may also be provided a cosmetic or personal care product comprising a composition as provided herein as described above and a cosmetically acceptable carrier.

In another embodiment, the cosmetic or personal care product is a gel.

Accordingly, the present invention provides a convenient and effective wrinkle removal product and method without side effects.

Drawings

FIG. 1 is a graph of results of an effect example.

Detailed Description

The inventor finds that the acetyl hexapeptide-8 and the pentapeptide-18 are compounded for use, have good synergistic effect and better effect of inhibiting muscle contraction through extensive and intensive research. The present invention has been completed based on this finding.

As used herein, "Acetyl Hexapeptide-8 (Acetyl Hexapeptide-8)" refers to a substance having a CAS registry number of 616204-22-9.

As used herein, "pentapeptide-18" refers to a substance having the pentapeptide sequence H-Tyr-D-Ala-Gly-Phe-Leu-OH.

As used herein, "moisturization" refers to the moisturization of the skin. When the air temperature is reduced, the skin cuticle can not timely adjust enough moisturizing factors, the activity of oil glands is reduced, the oil and water on the face are reduced, the skin can be tightened, and fine wrinkles can even appear under the eyes and near the nose.

As used herein, "hyaluronic acid" refers to a polymer having a molecular weight of 200-220 ten thousand and having the structure shown below:

as used herein, "hyaluronate" refers to sodium hyaluronate or potassium hyaluronate.

In the present invention, "dynamic wrinkles" or "expression lines" are used interchangeably, and refer to wrinkles formed by long-term contraction of expression muscles, which are mainly expressed in the raised eyebrow lines of the frontal muscles, the glabellar lines of the frown muscles, the crow's feet lines of the orbicularis oculi muscles, the canthus lines and the striae labialis, the zygomatic muscles, and the buccal twills of the upper labial quadratus.

In the present invention, the "gravitational wrinkles" are wrinkles formed by sagging and local folding of skin and muscle due to gravity. Common symptoms include eye bags, senile upper eyelid sagging skin, and double lower jaws.

The term "an effective amount" is intended to mean an amount that, after an appropriate period of use, provides an improvement in Wrinkle Severity Rating (WSRS) for wrinkle removal purposes.

"composition" refers to a composition that, when applied to an individual (typically a human), is capable of penetrating the skin to induce the desired wrinkle removal effect.

As used herein, the term "cosmetically acceptable carrier" refers to a carrier that allows a cosmetic or personal care product to be applied, including various excipients and diluents, which are not themselves essential active ingredients, and which do not have undue toxicity after application. Suitable carriers are well known to those of ordinary skill in the art. A sufficient discussion of cosmetically acceptable excipients can be found in the cosmetic hygiene specifications 2015 edition. Such carriers may include humectants, emulsifiers, thickeners, chelating agents, emollients, and the like in the composition.

The term "administering" as used herein means directly applying the composition to form a substantial amount of the composition on the skin of the individual to whom it is applied.

The terms "individual" or "individual" and the like are used herein to refer to a person who can receive the compositions and/or methods for application to the skin.

The inventor combines pentapeptide-18 and acetyl hexapeptide-8 in a mass ratio of 1:0.5-3.5, preferably 1:1-3.5, more preferably 1:1-3, and most preferably 1: 1.5-2.5. When the composition containing acetyl hexapeptide-8 and pentapeptide-18 is in a liquid state or gel state, the pH value is controlled to be 6-7.6, preferably 6.4-7.0, more preferably 6.6-6.8. The present invention maintains the pH within the desired range by using a buffer system, which may be phosphate buffer, acetate, sodium formate, or barbiturate sodium. The composition provided by the invention can also contain some components with moisturizing effect, such as but not limited to hyaluronic acid or salt thereof, glycerol, collagen and mucopolysaccharide.

In one embodiment of the invention, the composition provided by the invention is obtained by mixing acetyl hexapeptide-8, pentapeptide-18 and water.

In another embodiment of the present invention, the preparation may be carried out by the following steps:

firstly, respectively preparing a buffer solution, a solution containing a component with a moisturizing effect, a solution containing acetyl hexapeptide-8 and a solution containing pentapeptide-18;

and secondly, mixing the solutions prepared in the first step to obtain the composition provided by the invention.

In one embodiment of the present invention, the buffer solution in the first step is prepared by mixing 1/15mol/L potassium dihydrogen phosphate mother liquor (1 mol potassium dihydrogen phosphate in 15L mother liquor) and 1/15mol/L disodium hydrogen phosphate mother liquor (1 mol disodium hydrogen phosphate in 15L mother liquor) according to the following ratio: and (3) preparing a phosphate buffer solution by using the disodium hydrogen phosphate mother liquor as 1:49-11.5: 1.

In one embodiment of the present invention, the solution containing the component having moisturizing effect in the first step is obtained by adding the component having moisturizing effect to a buffer solution and mixing with stirring. Preferably, shaking or mechanical agitation may be used.

In one embodiment of the present invention, the solution containing acetyl hexapeptide-8 in the first step is obtained by mixing acetyl hexapeptide-8 with water; the solution containing pentapeptide-18 in the first step is obtained by mixing pentapeptide-18 with water.

In one embodiment of the invention, about 20 grams of glycerol and about 8 grams of hyaluronic acid or salt thereof are weighed into about 1000 milliliters of phosphate buffer and mixed thoroughly. Preparing pentapeptide-18 and acetyl hexapeptide-8 into mother liquor of about 10mg/ml, respectively, adding about 50ml of pentapeptide-18 mother liquor and about 50ml of acetyl hexapeptide-8 mother liquor into phosphate buffer solution containing glycerol and hyaluronic acid or its salt.

The mixing involved in the second step described above is not sonicatable.

In one embodiment of the invention, the second step is sterilized by microfiltration after mixing.

The compositions provided by the present invention may be used to remove wrinkles in an individual. In one embodiment of the present invention, the compositions provided herein may be mixed with a cosmetically acceptable carrier to provide a cosmetic or personal care product such as, but not limited to, a makeup cream, lotion, serum, gel, and the like.

Although numerical ranges and parameters setting forth the broad scope of the invention are approximate, the values set forth in the specific examples are presented as precisely as possible. Any numerical value, however, inherently contains certain standard deviations found in their respective testing measurements. As used herein, "about" generally means that the actual value is within plus or minus 10%, 5%, 1%, or 0.5% of a particular value or range. Alternatively, the term "about" means that the actual value falls within the acceptable standard error of the mean, as considered by those skilled in the art. Except in the experimental examples, or where otherwise expressly indicated, it is to be understood that all ranges, amounts, values and percentages herein used (e.g., to describe amounts of materials, length of time, temperature, operating conditions, quantitative ratios, and the like) are to be modified by the word "about". Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained. At the very least, these numerical parameters are to be understood as meaning the number of significant digits recited and the number resulting from applying ordinary carry notation.

Unless defined otherwise herein, the scientific and technical terms used herein have the same meaning as is commonly understood and used by one of ordinary skill in the art. Furthermore, as used herein, the singular tense of a noun, unless otherwise conflicting with context, encompasses the plural form of that noun; the use of plural nouns also covers the singular form of such nouns.

To make the features and effects of the present invention comprehensible to those skilled in the art, general description and definitions are made below with reference to terms and expressions mentioned in the specification and claims. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

The theory or mechanism described and disclosed herein, whether correct or incorrect, should not limit the scope of the present invention in any way, i.e., the present disclosure may be practiced without limitation to any particular theory or mechanism.

All features defined herein as numerical ranges or percentage ranges, such as values, amounts, levels and concentrations, are for brevity and convenience only. Accordingly, the description of numerical ranges or percentage ranges should be considered to cover and specifically disclose all possible subranges and individual numerical values (including integers and fractions) within the range.

The features mentioned above with reference to the invention, or the features mentioned with reference to the embodiments, can be combined arbitrarily. All features disclosed in this specification may be combined in any combination, provided that there is no conflict between such features and the combination, and all possible combinations are to be considered within the scope of the present specification. Each feature disclosed in this specification may be replaced by an alternative feature serving the same, equivalent, or similar purpose. Thus, unless expressly stated otherwise, the features disclosed are merely generic examples of equivalent or similar features.

The main advantages of the invention are:

the composition provided by the invention can effectively remove expression lines, and the active substances of the composition are low in cost and suitable for the public.

The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The experimental procedures, in which specific conditions are not noted in the following examples, are generally carried out according to conventional conditions or according to conditions recommended by the manufacturers. All percentages, ratios, proportions, or parts are by weight unless otherwise specified. The weight volume percentage units in the present invention are well known to those skilled in the art and refer to, for example, the weight of solute in a 100 ml solution. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In addition, any methods and materials similar or equivalent to those described herein can be used in the methods of the present invention. The preferred embodiments and materials described herein are intended to be exemplary only.

Preparation examples

The groups of samples were prepared according to the following table:

wherein, the preparation of the phosphate buffer solution comprises the steps of firstly preparing 1/15mol/L potassium dihydrogen phosphate mother liquor and 1/15mol/L disodium hydrogen phosphate mother liquor respectively, and then preparing the following raw materials according to the weight ratio of the potassium dihydrogen phosphate mother liquor: the disodium hydrogen phosphate mother liquor is 1:49-11.5:1, and the two mother liquors are mixed to obtain a phosphate buffer solution.

Preparation method of each group of samples:

weighing glycerol and sodium hyaluronate, adding phosphate buffer solution, and stirring to fully dissolve to obtain solution 1;

weighing acetyl hexapeptide-8, dissolving in water for injection, and stirring to dissolve to obtain a solution 2;

weighing pentapeptide-18, dissolving in water for injection, and stirring to dissolve to obtain solution 3;

and measuring the solution 2 and the solution 3, adding the solution into the solution 1, uniformly mixing, and sterilizing through a 0.22-micron microporous filter membrane to obtain a sample.

The sample may be used in sterile-filled containers commonly used in the art, such as, but not limited to, vials, prefilled syringes, ampoules, dropper bottles, and the like.

Effects of the embodiment

Subject: subjects with Wrinkle Severity Rating (WSRS) of moderate (iv-grade) were used.

Wrinkle severity grading (WSRS):

the I level has no visible crease and only has continuous skin lines;

the grade II wrinkles are shallow but can be seen to be slight dents, and the facial wrinkles are fine;

grade III deep wrinkles, the facial creases are clear, the creases are visible under normal conditions, but the creases disappear when the facial creases are stretched;

very long and deep wrinkles of grade IV, remarkable facial wrinkles, visible wrinkles less than 2mm when stretched;

the extreme deep and long wrinkles of class V severely detract from the face appearance, with clearly visible V-folds of 2-4mm when extended.

The test method comprises the following steps: by adopting an injection introduction mode, the subjects can be scored at follow-up visit when using for one month.

Evaluation of the effects: there were 5 grading scores based on the general facial cosmetic improvement (GAIS) condition: 0 is worsened; 1 is invalid; 2, the effect is slightly improved; 3, obviously improving; 4 is a complete improvement.

The results are shown in the following table and in FIG. 1.

Stability test

PBS buffers with different pH values were prepared, samples were prepared according to the amounts of other raw material components of the above test group two, and stored at 37 ℃ for 90 days, and the content of remaining peptides in the solution was measured by HPLC, and the results are shown in the following table.

The HPLC determination method comprises the following steps: octadecylsilane chemically bonded silica is used as a filling agent, 0.05mol/L phosphate buffer solution-methanol (90:10) is used as a mobile phase, the detection wavelength is 275nm, and the sample injection amount is 20 microliters.

The foregoing is merely a preferred embodiment of the invention and is not intended to limit the scope of the invention, which is defined by the claims appended hereto, and any other technical entity or method that is encompassed by the claims as broadly defined herein, or equivalent variations thereof, is contemplated as being encompassed by the claims.

Claims

1. A composition comprising acetyl hexapeptide-8 and pentapeptide-18.

2. The composition of claim 1, wherein the mass ratio of pentapeptide-18 to acetyl hexapeptide-8 is 1: 0.5-3.5.

3. The composition of claim 1, further comprising a moisturizing component.

4. The composition of claim 3, wherein the moisturizing component is selected from one or more of the following: hyaluronic acid or a salt thereof, glycerol, collagen, and mucopolysaccharide.

5. The composition of claim 1, further comprising a buffer to provide a pH of 6 to 7.6 when the composition is in a liquid or gel state.

6. The composition of claim 5, wherein the buffer is selected from the group consisting of phosphate, acetate, sodium formate, or barbiturate.

7. The composition according to any one of claims 1 to 6, wherein the composition comprises:

8. the composition of claim 7, further comprising a balance of water.

9. A method of preparing a composition according to any one of claims 1 to 8, comprising the steps of: mixing the solution containing acetyl hexapeptide-8 and pentapeptide-18 with a buffer and a moisturizing ingredient to obtain the composition of any one of claims 1-8.

10. Use of a composition according to any of claims 1 to 8 for removing wrinkles or for the preparation of a cosmetic or personal care product for removing wrinkles.