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CN-121974973-A - Novel crystal form of acetyl tetrapeptide-5, and preparation method and application thereof

CN121974973ACN 121974973 ACN121974973 ACN 121974973ACN-121974973-A

Abstract

The invention relates to the technical field, in particular to a novel crystal form of acetyl tetrapeptide-5, a preparation method and application thereof, wherein an X-ray powder diffraction pattern of the novel crystal form of acetyl tetrapeptide-5 has diffraction peaks at 2 theta +/-0.2 degrees, and the 2 theta comprises 8.292 degrees, 16.541 degrees, 18.522 degrees, 21.825 degrees and 24.701 degrees. The invention solves the problems of easy moisture absorption and poor thermal stability of the conventional acetyl tetrapeptide-5 freeze-dried powder, and the prepared crystal has obviously better moisture absorption resistance and temperature stability than the commercial freeze-dried powder, and has wide application prospect. In addition, the invention further develops a crystallization process of the stable crystal form of the acetyl tetrapeptide-5, and the process can finish solid-liquid separation and drying processes in a conventional enamel reaction kettle and a vacuum dryer, does not need to adopt a freeze dryer with small batch and high energy consumption, and is more suitable for industrial production.

Inventors

  • ZHANG ZHANG
  • DENG PENGHUA
  • PAN JUNFENG
  • LIU JIAN

Assignees

  • 深圳瑞德林生物技术有限公司

Dates

Publication Date
20260505
Application Date
20260206

Claims (10)

  1. 1. A novel crystalline form of acetyl tetrapeptide-5, wherein the X-ray powder diffraction pattern has diffraction peaks at 2Θ ± 0.2 ° positions, said 2Θ comprising 8.292 °, 16.541 °, 18.522 °, 21.825 ° and 24.701 °.
  2. 2. The novel crystalline form of acetyl tetrapeptide-5 according to claim 1, wherein the 2Θ comprises 8.292 °, 16.541 °, 17.96 °, 18.522 °, 19.981 °, 21.53 °, 21.825 °, 24.701 °, and 25.89 °.
  3. 3. The novel crystalline form of acetyl tetrapeptide-5 according to claim 1, wherein the X-ray powder diffraction pattern is shown in figure 2.
  4. 4. The preparation method of the novel crystal form of acetyl tetrapeptide-5 comprises the following steps: and (3) enabling the water solution of the acetyl tetrapeptide-5 to contact with acetone, and crystallizing to obtain a novel crystal form of the acetyl tetrapeptide-5.
  5. 5. The method according to claim 4, wherein the concentration of the aqueous solution of acetyl tetrapeptide-5 is 100-1000 g/L.
  6. 6. The preparation method of claim 4, wherein the volume ratio of the aqueous solution of acetyl tetrapeptide-5 to acetone is 1 (1-5).
  7. 7. The method according to claim 4, wherein the aqueous solution of acetyl tetrapeptide-5 is contacted with acetone by dropwise addition or by flow-through addition.
  8. 8. The preparation method according to claim 4, wherein the temperature at which the aqueous solution of acetyl tetrapeptide-5 is contacted with acetone is 15-45 ℃; the crystallization temperature is 5-15 ℃; The crystallization time is 8-24 hours.
  9. 9. The method according to claim 4, wherein the crystallization is performed by cooling to 5-15 ℃ at a rate of 5-10 ℃ per hour.
  10. 10. Use of the novel crystalline form of acetyl tetrapeptide-5 according to any one of claims 1 to 3 or the novel crystalline form of acetyl tetrapeptide-5 prepared by the preparation method according to any one of claims 4 to 9 in the preparation of cosmetics.

Description

Novel crystal form of acetyl tetrapeptide-5, and preparation method and application thereof Technical Field The invention relates to the technical field, in particular to a novel crystal form of acetyl tetrapeptide-5, and a preparation method and application thereof. Background Acetyl tetrapeptide-5 (Ac-beta Ala-His-Ser-His-OH) is also known as oculoplasm aminopeptide or lixivium peptide, and can inhibit angiotensin I (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu) from being cracked into angiotensin II (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe) acting on blood constriction vessels by inhibiting angiotensin converting enzyme ACE-1, thereby playing the roles of dilating blood vessels and eliminating edema, eye bags and dark circles. At present, the product of the acetyl tetrapeptide-5 is mainly sold in the forms of water, butanediol, the acetyl tetrapeptide-5 or two liquid formulations of glycerol, water and the acetyl tetrapeptide-5, and the price is high. The freeze-dried powder is sold in a freeze-dried powder form, but the freeze-dried powder has inherent problems of easy moisture absorption, poor thermal stability and the like, has strict requirements on storage conditions, and generally needs to be stored under freezing or refrigerating conditions. Meanwhile, the freeze-dried powder is limited by freeze-drying equipment, and the production batch is small and the cost is high. These have greatly limited the widespread use of acetyl tetrapeptide-5 in the cosmetic field. Disclosure of Invention In view of the above, the technical problem to be solved by the invention is to provide a novel crystal form of acetyl tetrapeptide-5, and a preparation method and application thereof, wherein the novel crystal form of acetyl tetrapeptide-5 has higher stability. In order to solve the technical problems, the invention provides a novel crystal form of acetyl tetrapeptide-5, wherein an X-ray powder diffraction pattern has diffraction peaks at the position of 2 theta plus or minus 0.2 degrees, and the 2 theta comprises 8.292 degrees, 16.541 degrees, 18.522 degrees, 21.825 degrees and 24.701 degrees. Further, the 2θ includes 8.292 °, 16.541 °, 17.96 °, 18.522 °, 19.981 °, 21.53 °, 21.825 °, 24.701 °, and 25.89 °. Specifically, the X-ray powder diffraction pattern of the novel crystalline form of acetyl tetrapeptide-5 is shown in fig. 2, and the specific diffraction peak positions are shown in table 1. In the present invention, the 2 theta values of the X-ray powder diffraction patterns may vary slightly between machines or between samples, and the values may differ by about 0.2 units, or by about 0.1 units, so that the values recited are not to be construed as absolute values. It should also be understood that the peak heights may likewise differ in size by about 5 units, or by about 4 units, or by about 3 units, or by about 2 units, or by about 1 unit, and thus the XRPD trace (trace) intensities included in the present invention are illustrative and not intended for absolute comparison. The invention provides a preparation method of the novel crystal form of acetyl tetrapeptide-5, which comprises the following steps: and (3) enabling the water solution of the acetyl tetrapeptide-5 to contact with acetone, and crystallizing to obtain a novel crystal form of the acetyl tetrapeptide-5. The concentration of the aqueous solution of acetyl tetrapeptide-5 is 100-1000 g/L, more preferably 300-600 g/L, and can be 300, 400, 500 and 600g/L. The volume ratio of the aqueous solution of acetyl tetrapeptide-5 to acetone is 1 (1-5), more preferably 1 (2-4), and can be 1:2, 1:3 and 1:4 by way of example. Preferably, acetone is added to the aqueous solution of acetyl tetrapeptide-5. The mode of addition of the present invention is not particularly limited, and includes, but is not limited to, dropping, feeding, etc. Preferably, the method of feeding is adopted. The feeding speed is preferably 40-60 mL/h, and can be 40, 50 and 60mL/h by way of example. Preferably, the feeding is performed under the condition of stirring the system. The stirring speed is preferably 100 to 500rpm, more preferably 200 to 400rpm, and may be 200, 300, 400rpm, for example. The temperature of the aqueous solution of acetyl tetrapeptide-5 contacted with acetone is preferably 15-45 ℃, more preferably 20-30 ℃, and may be 20, 25 or 30 ℃ by way of example. The crystallization temperature is preferably 5 to 15 ℃, more preferably 6 to 10 ℃, and may be 6, 7, 8, 9, or 10 ℃ by way of example. The crystallization time is preferably 8-24 hours, more preferably 10-20 hours, and may be, for example, 10, 12, 15, 20 hours, 24 hours. Preferably, the crystallization is specifically performed by cooling to 5-15 ℃ at a speed of 5-10 ℃ per hour. The cooling speed is more preferably 6-8 ℃ per hour, and can be 6, 7 and 8 ℃ per hour by way of example. After crystallization, the obtained crystal is filtered, washed and dried. In some preferred embodiments, the above-described preparation method compr