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KR-20260064990-A - Phamarceutical Composition For Preventing Or Treating Pain

KR20260064990AKR 20260064990 AKR20260064990 AKR 20260064990AKR-20260064990-A

Abstract

The present invention relates to a composition for preventing or treating pain, and specifically, to a pharmaceutical composition, food composition, health functional food, quasi-drug composition, feed composition, and cosmetic composition for preventing, treating, or improving pain, comprising a peptide, a fragment thereof, or an analog thereof as an active ingredient, and a method for preventing or treating pain. Since the composition of the present invention possesses an inhibitory effect on pain, it can be usefully utilized as a composition for the prevention, treatment, and improvement of diseases accompanied by pain in general. Furthermore, in accordance with market trends showing an increasing demand for non-narcotic analgesics, it is expected that the present invention can be applied to the development of analgesics capable of controlling pain of various causes.

Inventors

  • 황선욱
  • 김민석
  • 하이옌 장

Assignees

  • 고려대학교 산학협력단

Dates

Publication Date
20260508
Application Date
20241030

Claims (20)

  1. A pharmaceutical composition for the prevention or treatment of pain comprising, as an active ingredient, a peptide consisting of the amino acid sequence of SEQ ID NO. 1, a fragment thereof, or an analog thereof.
  2. In paragraph 1, A peptide, a fragment thereof, or an analog thereof composed of the amino acid sequence of SEQ ID NO. 1 is, A pharmaceutical composition in which one or more selected from the group consisting of the 1st, 2nd, 3rd, 6th, and 10th amino acids from the N-terminus in the amino acid sequence of SEQ ID NO. 1 are substituted with D-Nal (2), D-Phe (pCl), D-Pal (3), D-Cit, or D-Ala.
  3. In paragraph 1, A peptide, a fragment thereof, or an analog thereof composed of the amino acid sequence of SEQ ID NO. 1 is, From the N-terminus of the amino acid sequence of SEQ ID NO. 1, The first amino acid is substituted with D-Nal(2); The second amino acid is substituted with D-Phe(pCl); The 3rd amino acid is substituted with D-Pal(3); The 6th amino acid is substituted with D-Cit; and A pharmaceutical composition in which the 10th amino acid is substituted with D-Ala.
  4. In paragraph 1, A pharmaceutical composition comprising a peptide, a fragment thereof, or an analog thereof consisting of the amino acid sequence of SEQ ID NO. 1, wherein the C-terminus is amidated and the N-terminus is acetylated.
  5. In paragraph 1, A pharmaceutical composition wherein the above pain is one or more selected from the group consisting of neuropathic pain, inflammatory pain, osteoarthritis pain, postoperative pain, cancer pain, pain associated with metastatic cancer, pain caused by cancer treatment chemotherapy agents, trigeminal neuralgia, burning pain, acute herpes and post-herpetic neuralgia, occipital neuralgia, sympathetic dystrophy, fibromyalgia, gouty pain, burn pain, phantom limb pain, complex regional pain syndrome, idiopathic pain syndrome, migraine, and chronic pain of unknown cause.
  6. In paragraph 5, A pharmaceutical composition in which the above-mentioned neuropathic pain is caused by peripheral nerve trauma, herpes virus infection, diabetes, brachial plexus resection, neuroma, limb amputation and vasculitis, chronic alcoholism, human immunodeficiency virus infection, hypothyroidism, uremia, nerve injury due to vitamin deficiency, side effects of anticancer drugs, peripheral nerve damage, central nerve damage, cancer, immunodeficiency, trauma, ischemia, multiple sclerosis, sciatica, trigeminal neuralgia, fibromyalgia, or post-herpetic syndrome.
  7. In paragraph 5, A pharmaceutical composition wherein the above-mentioned neuropathic pain comprises one or more symptoms selected from the group consisting of cold allodynia, mechanical allodynia, spontaneous pain, paresthesiasis, dysesthesiasis, hyperalgesia, and hyperpathia.
  8. A food composition for preventing or improving pain comprising, as an active ingredient, a peptide consisting of the amino acid sequence of SEQ ID NO. 1, a fragment thereof, or an analog thereof.
  9. In paragraph 8, A food composition wherein the above pain is one or more selected from the group consisting of neuropathic pain, inflammatory pain, osteoarthritis pain, postoperative pain, cancer pain, pain associated with metastatic cancer, pain caused by cancer treatment chemotherapy agents, trigeminal neuralgia, burning pain, acute herpes and post-herpetic neuralgia, occipital neuralgia, sympathetic dystrophy, fibromyalgia, gouty pain, burn pain, phantom limb pain, complex regional pain syndrome, idiopathic pain syndrome, migraine, and chronic pain of unknown cause.
  10. In Paragraph 9, A food composition in which the above-mentioned neuropathic pain is caused by side effects of anticancer drugs, peripheral nerve damage, central nerve damage, diabetes, cancer, immunodeficiency, trauma, ischemia, multiple sclerosis, sciatica, trigeminal neuralgia, fibromyalgia, or post-herpetic syndrome.
  11. In Paragraph 9, A food composition wherein the above-mentioned neuropathic pain comprises one or more symptoms selected from the group consisting of cold allodynia, mechanical allodynia, spontaneous pain, paresthesiasis, dysesthesiasis, hyperalgesia, and hyperpathia.
  12. A health functional food for preventing or improving pain, comprising as an active ingredient a peptide consisting of the amino acid sequence of SEQ ID NO. 1, a fragment thereof, or an analog thereof.
  13. A quasi-drug composition for preventing or improving pain, comprising as an active ingredient a peptide consisting of the amino acid sequence of SEQ ID NO. 1, a fragment thereof, or an analog thereof.
  14. In Paragraph 13, A quasi-drug composition wherein the above pain is one or more selected from the group consisting of neuropathic pain, inflammatory pain, osteoarthritis pain, postoperative pain, cancer pain, pain associated with metastatic cancer, pain caused by cancer treatment chemotherapy agents, trigeminal neuralgia, burning pain, acute herpes and post-herpetic neuralgia, occipital neuralgia, sympathetic dystrophy, fibromyalgia, gouty pain, burn pain, phantom limb pain, complex regional pain syndrome, idiopathic pain syndrome, migraine, and chronic pain of unknown cause.
  15. In Paragraph 13, The above quasi-drug composition is formulated as an external preparation, powder, disinfectant, toothpaste, ointment, lotion, oral preparation, wet wipe, spray patch, bandage, or patch.
  16. A feed composition for preventing or improving pain comprising, as an active ingredient, a peptide consisting of the amino acid sequence of SEQ ID NO. 1, a fragment thereof, or an analog thereof.
  17. In Paragraph 16, A feed composition wherein the above pain is one or more selected from the group consisting of neuropathic pain, inflammatory pain, osteoarthritis pain, postoperative pain, cancer pain, pain associated with metastatic cancer, pain caused by cancer treatment chemotherapy agents, trigeminal neuralgia, burning pain, acute herpes and post-herpetic neuralgia, occipital neuralgia, sympathetic dystrophy, fibromyalgia, gouty pain, burn pain, phantom limb pain, complex regional pain syndrome, idiopathic pain syndrome, migraine, and chronic pain of unknown cause.
  18. A cosmetic composition for preventing or improving pain comprising, as an active ingredient, a peptide consisting of the amino acid sequence of SEQ ID NO. 1, a fragment thereof, or an analog thereof.
  19. In Paragraph 18, A cosmetic composition wherein the above pain is one or more selected from the group consisting of neuropathic pain, inflammatory pain, osteoarthritis pain, postoperative pain, cancer pain, pain associated with metastatic cancer, pain caused by cancer treatment chemotherapy agents, trigeminal neuralgia, burning pain, acute herpes and post-herpetic neuralgia, occipital neuralgia, sympathetic dystrophy, fibromyalgia, gouty pain, burn pain, phantom limb pain, complex regional pain syndrome, idiopathic pain syndrome, migraine, and chronic pain of unknown cause.
  20. A method for preventing or treating pain comprising the step of administering to an individual other than a human a composition comprising, as an active ingredient, a peptide consisting of the amino acid sequence of SEQ ID NO. 1, a fragment thereof, or an analog thereof.

Description

Pharmaceutical Composition for Preventing or Treating Pain The present invention relates to a composition for preventing or treating pain, and specifically, to a pharmaceutical composition, food composition, health functional food, quasi-drug composition, feed composition, and cosmetic composition for preventing, treating, or improving pain, comprising a peptide, a fragment thereof, or an analog thereof as an active ingredient, and a method for preventing or treating pain. Pain is a serious condition that impairs both an individual's quality of life and social productivity. Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Although pain manifests as a major symptom in various diseases, its perception is highly subjective, making it one of the most difficult pathologies to diagnose and treat effectively. Pain leads to severe impairment of functional abilities and jeopardizes a patient's work, social, and family life. Such pain is highly diverse and includes neuropathic pain, inflammatory pain, osteoarthritis pain, postoperative pain, cancer pain, pain associated with metastatic cancer, pain caused by chemotherapy agents, trigeminal neuralgia, burning pain, acute and post-herpetic neuralgia, occipital neuralgia, sympathetic dystrophy, fibromyalgia, gouty pain, burn pain, phantom limb pain, complex regional pain syndrome, idiopathic pain syndrome, migraine, and chronic pain of unknown cause. Currently available analgesics, such as anesthetics and non-steroidal anti-inflammatory drugs, are known to fail to completely eliminate pain due to insufficient efficacy or side effects, thus necessitating the emergence of new technologies. Accordingly, the inventors intend to provide a novel composition with a pain-inhibiting effect that has not been reported to date, and a method for suppressing pain using the same. Figure 1 is the result of confirming the pain-inhibiting effect on mechanical allodynia hypersensitivity according to the treatment of the peptide of the present invention. Figure 2 is the result of confirming the pain-inhibiting effect on mechanical hyperalgesia following treatment with the peptide of the present invention. The present invention will be explained in more detail below through the following examples. However, these examples are intended to illustrate the invention and the scope of the invention is not limited to these examples. Example 1. Confirmation of pain suppression for neuropathic allodynia hypersensitivity induced by chronic sciatic nerve contraction injury The pain-inhibiting effect of the peptide Ac-D-Nal(2)-D-Phe(pCl)-D-Pal(3)-Ser-Tyr-D-Cit-Leu-Arg-Pro-D-Ala-NH 2 (hereinafter referred to as Compound 1, Chemical 1) on allodynia hypersensitivity was analyzed using a neuropathic pain model of chronic constriction injury (CCI), which is a type of standardized pain model. The peptide of Compound 1 is a peptide in which an acetyl group is added to the N-terminus and an amide group to the C-terminus of the amino acid sequence of SEQ ID NO. 1, and the 1st, 2nd, 3rd, 6th, and 10th amino acids from the N-terminus are substituted with D-type or/and non-standard amino acids. Specifically, a neuropathy-inducing surgery was performed in which the sciatic nerve of one femur of a mouse was externally exposed and the nerve was loosely ligated three times with surgical sutures to induce nerve damage. Consequently, the peptide of the present invention was administered to male C57BL/6 mice two weeks after peak hyperalgesia had occurred. The effect of Compound 1 on neuropathic hyperalgesia was measured using mice before and after administration. Baseline (BL) measurements were obtained before the surgery. The results were presented as the average of 5 mice per group. The sham group was performed by exposing the sciatic nerve but omitting the ligation step (a process that induces nerve damage in the CCI model), and the control group was treated with an excipient. First, the effect of Compound 1 on mechanical allodynia was evaluated using a von Frey filament (Stoelting, Illinois, USA). Mice were placed in a cage with a wire mesh floor to allow access to the filament on their soles. Before starting the experiment, the mice were acclimatized to the environment. The surface of the mouse's hind paw was stimulated with the von Frey filament for approximately 5 seconds, while increasing the force until the pain response, the paw-lifting response, was induced. When the paw-lifting response occurred due to filament stimulation of a specific intensity, the force of the von Frey filament was lowered, and the paw stimulation was retested until no response occurred. If there was no paw-lifting response, the force of the von Frey filament was increased, and the paw stimulation was retested until a response occurred. The intensity of the force used to induce the foot-lifting response was set as the Paw Withdrawal Threshold (PWT), and if the PWT was stat