A Clinical Study of Freshly Manufactured 35kDa Hyaluronan Fragment in the Treatment of Pain
Condition: Shoulder Pain; Neck Pain; Back Pain; Temporal Pain; Herpes Zoster Pain
MeSH terms: Herpes Simplex; Herpes Zoster; Shoulder Pain; Neck Pain
Study type: Interventional

Summary: 
      Local used high molecular weight Hyaluronan (HA) with high viscosity has a variety of
      receptors in the human body, including CD44, LYVE-1, RHAMM, HARE, Siglec-9, TLR2, CEMIP and
      TMEM2. Intra-articular local injection of HA has a certain degree of analgesic effect. Local
      injection of HA into the nerve trunk directed by ultrasound was used for the treatment of
      neuropathic pain. It was reported that the analgesic effect of HA is regulated by TRPV1 ion
      channels. This study hypothesizes that hyaluronidase cleaves HA to generate low molecular
      weight HA fragments HA35 with good tissue permeability, which may bind to a variety of HA
      receptors on the cell surface within the tissues and produce a broad-spectrum analgesic
      effect. In this study, 35kDa Hyaluronan fragment HA35 was prepared by mixing hyaluronidase
      PH20 injection and high molecular weight Hyaluronan (HA) injection at room temperature for 20
      minutes. In this study, hyaluronidase injection and Hyaluronan injection were off-label used
      to conduct an investigator-initiated study (IIT or IIS) for the treatment of herpes zoster
      and shoulder, neck, back and temporal pain.
    

Detailed description: 
      Bioactive Hyaluronan fragment HA35 of 35kDa was isolated from human colostrum. Literature
      studies have shown that female breast hyaluronidase and male testicular sperm acrosomal
      hyaluronidase PH20 come from the same gene. The investigators, recombinant human
      hyaluronidase PH20 and neutral hyaluronidase (PH20 or SPAM1) of bovine testicular sperm
      acrosome were used to cleave macromolecular Hyaluronan. Regardless of the cutting time, the
      Hyaluronan fragment HA35 with an average molecular weight 35kDa was produced(Registration
      number L20200708MP07707, Ministry of Health, Mongolia). Hyaluronidase injection is often used
      to improve the penetration and absorption of other injectable drugs. Hyaluronidase injection
      is also used to degrade excessive use of cosmetic injection or improper use of cross-linked
      macromolecular Hyaluronan fillers, which is an off-label drug use of
      hyaluronidase（https://www.realself.com/news/ hyaluronidase-dissolve-fillers）. In this study,
      Hyaluronan fragment HA35 of 35kDa was prepared by mixing hyaluronidase injection extracted
      from bovine testis (hyaluronidase for injection, H31022111) and Hyaluronan injection (sodium
      hyaluronate injection, H20174089) at room temperature for 20 minutes. Its analgesic effect on
      herpes zoster, shoulder, neck, back, and temporal pain was studied.

      In this study, off-label drug use of hyaluronidase injection and Hyaluronan injection
      （https://www.realself.com/news/ hyaluronidase-dissolve-fillers）were used in the clinical
      study of shoulder, neck, back and temporal pain and herpes zoster pain, namely investigator
      initiated trails. In this clinical trial, 26 patients with shoulder, neck, back and temporal
      pain were studied in the Department of pain diagnosis and treatment of the affiliated
      Hospital of Qingdao University. Ten patients with herpes zoster were treated in the pain
      Department of the affiliated Hospital of Qingdao University. According to the ratio of 100mg
      high molecular Hyaluronan / 2000 unit hyaluronidase, the high molecular Hyaluronan injection
      (sodium hyaluronate injection, H20174089) and the hyaluronidase injection extracted from
      bovine testis (hyaluronidase for injection) were mixed at room temperature for 20 minutes.
      Each time according to the amount of high molecular Hyaluronan containing 100 mg Hyaluronan
      and hyaluronidase mixture, pain point area and pain point area of the nerve trunk innervation
      of the local multi-point injection. Then, pain scale was used to evaluate and record the pain
      relief of patients before and after treatment.
    

Intervention name(s): HA35(L20200708MP07707, Ministry of Health, Mongolia) was freshly manufactured by mixing hyaluronidase PH20 injectable solution (H31022111) and high-molecular-weight HA injectable solution (H20174089)
Intervention type(s): Drug
Intervention description(s): This group will inject once a week. Evaluation of pain score after 30 seconds and 3 hours.
Other intervention name(s): HA35
Intervention MeSH terms: Pharmaceutical Solutions
Intervention model: Single Group Assignment
Intervention model description: A self-controlled an open label clinical study(An investigator-initiated off-label use clinical study)
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: hyaluronidase; Hyaluronan; 35kDa Hyaluronan fragment; pain caused by herpes zoster; pain caused by shoulder neck back and temporal