13.6% HA35 nasopharyngeal gel · 10-day case series · n=7

Seven adults with chronic rhinitis and pharyngitis used a 13.6% high-concentration HA35 nasopharyngeal gel twice daily for 10 consecutive days.

Within 30 minutes after the first application:

• Nasopharyngeal discomfort / sneezing: 4.6 ± 1.4 → 0.6 ± 0.4 (−87.0%)

• Posterior pharyngeal discomfort / cough: 4.0 ± 0.8 → 0.4 ± 0.6 (−90.0%)

• Perceived nasal obstruction: 4.6 ± 1.0 → 0.6 ± 0.4 (−87.0%)

After 10 days:

• Rhinitis-related symptom score: 4.2 ± 1.4 → 0.6 ± 0.6

• Pharyngitis-related symptom score: 5.8 ± 1.8 → 0.8 ± 0.6

All participants also reported improved subjective mental clarity within 1–3 hours after the first morning administration.

Reference

Hui J, Jia X, Li X, et al. Rapid Relief of Nasopharyngeal and Posterior Pharyngeal Inflammatory Symptoms After Nasopharyngeal Administration of High-Concentration 35 kDa Hyaluronan: A Case Series.

World Journal of Advanced Research and Reviews. 2026;29(1):1271–1276.

DOI: 10.30574/wjarr.2026.29.1.0076

10% HA35 periocular gel · 7-day case series · n=7

Seven adults applied 10% 35 kDa HA35 gel around the closed eyes under occlusion for more than 2 hours or overnight, once daily for seven consecutive days.

20 minutes after the first application:

• Ocular discomfort / pain / itch: 3.14 ± 0.89 → 0.42 ± 0.53 (−86.6%)

• Ocular fatigue: 2.85 ± 0.69 → 0.28 ± 0.48 (−90.2%)

After seven applications:

• Ocular discomfort / pain / itch: 3.14 → 0

• Ocular fatigue: 2.85 → 0

• Reduced perceived visual brightness: 1.85 → 0

• Ocular / palpebral conjunctival score: 3.14 → 0

• Upper-eyelid thickness score: 2.14 → 0

• Lateral canthal wrinkle score: 1.57 → 0.71

Palpebral fissure appearance and periocular tissue softness also improved. Two daily contact-lens users reported marked reductions in dryness, redness, swelling, and itching. No treatment-related adverse events were reported. Manuscript.docxDOCX

Outcomes were based on study-specific 0–10 scores and photographic observations in an uncontrolled case series.

A. Topical HA35 — Facial Appearance

10% HA35 topical gel · 10-day case series · n=5

Five adults applied a 10% 35 kDa HA35 formulation to the entire face under overnight occlusion once every two days, for a total of five applications.

After five applications:

• Forehead subcutaneous-fullness score: 3.6 → 0.8 (−77.8%)

• Cheek subcutaneous-fullness score: 4.2 → 1.0 (−76.2%)

• Nasal-alar subcutaneous-fullness score: 3.0 → 0.8 (−73.3%)

• Cheek inflammatory erythema: 3.2 → 0.2 (−93.8%)

• Nasal-alar pore enlargement: 3.0 → 0.6 (−80.0%)

Skin-radiance scores also improved across multiple facial regions, and visible changes were reported after the first overnight application.

Subcutaneous-fullness assessments were based on visual inspection and palpation using a 0–10 scale rather than imaging-based measurement.

Reference

Ding M, Jia X, Gao F, et al. Overnight Occlusive Topical Application of High-Concentration 35 kDa Hyaluronic Acid Fragments for Facial Erythema and Subcutaneous Fat: A Case Series.

International Journal of Advanced Research. 2026;14:488–493.

DOI: 10.21474/IJAR01/22560

B. Oral Defined-Molecular-Weight HA — Facial & Body Appearance

70 kDa HA · 5 g/day · 40-day case series · n=11

Participants maintained their usual diet and physical activity during the observation period.

Mean participant-reported contour scores after 40 days:

• Cheek fullness reduction: 7.2 / 10

• Double-chin reduction: 7.5 / 10

• Upper-eyelid thickness reduction: 7.2 / 10

• Upper-arm fullness reduction: 5.8 / 10

• Thigh fullness reduction: 5.8 / 10

• Abdominal fullness reduction: 6.4 / 10

9 of 11 participants scored both cheek and double-chin improvement at ≥7/10.

Mean body weight decreased by 4.2 kg during the 40-day observation period. Mean improvement scores for inflammatory facial erythema and facial vitality were both 5.5 / 10.

These were exploratory participant-reported outcomes; body composition was not objectively measured.

Reference

Ding M, Ma W, Jia X, et al. Exploratory Clinical Observations of High-Dose Oral 70 kDa Hyaluronan Fragments in Subcutaneous Fat Reduction, Inflammatory Erythema, and Facial Vitality: A Case Series.

Indian Journal of Pharmacy and Pharmacology. 2026;13(1):62–66.

HA35 & HA70 · Preclinical oral absorption study

Oral administration studies in rats compared two defined low-molecular-weight HA fractions, HA35 and HA70.

Key findings:

• Both HA35 and HA70 were rapidly detected in systemic circulation

• HA levels in the mesenteric lymph nodes increased significantly within 30 minutes after administration

• Mesenteric lymphatic transport was identified as a major absorption pathway

• Free HA showed no comparable increase in the liver or spleen during the observation period

These findings support direct intestinal uptake of defined low-molecular-weight HA fragments and highlight the mesenteric lymphatic system as an important route connecting oral administration with systemic exposure.

Separate radiotracer imaging studies have also detected orally administered 99mTc-labeled HA35 in mesenteric and other lymph nodes following gastrointestinal administration.

Reference

Dashnyam K, Shofaro J, Hui J, Jia X, Hui M. Rapid Lymphatic Absorption of Orally Administered Low-Molecular-Weight Hyaluronic Acid: A Pathway to the Bloodstream via Mesenteric Nodes.

Journal of Pharmaceutical Research International. 2025;37(5):133–147.

DOI: 10.9734/jpri/2025/v37i57698

10% HA35 gingival gel · 42-day case series · n=4

Four adults with mild gingival recession and chronic gingival or radicular discomfort applied 10% HA35 gel to the teeth and gingiva twice daily for 42 days.

After 42 days:

• Mean exposed root distance: 1.4 ± 0.2 mm → 0.2 ± 0.1 mm

• Mean observed gingival coverage increase: approximately 1.2 mm

• Chronic gingival / radicular pain score: 2.4 → 0

Additional observations included:

• Gingival itching and discomfort disappeared within approximately 30 seconds after application

• Redness and swelling improved markedly within 4 days

• Brushing-associated bleeding stopped within 2 days

• No adverse reactions were reported

These observations were reported in a small uncontrolled case series.

Reference

Hui M, Li Y, Jia X, Hui JH, Gorbunova V. Application of High-Concentration 35 kDa Hyaluronic Acid Fragment Gel in the Treatment of Mild Gingival Recession and Periodontal Inflammation: A Case Series.

Asian Journal of Dental Sciences. 2026;9(1):80–86.

DOI: 10.9734/ajds/2026/v9i1296

A. Neuropathic & Inflammatory Pain

Local HA35 injection · Clinical study · n=36

The study included:

• 10 patients with postherpetic neuralgia

• 26 patients with shoulder, neck, back, or temporomandibular inflammatory pain

At 180 minutes:

• Postherpetic neuralgia: 10/10 (100%) achieved ≥50% pain improvement

• Inflammatory pain: 26/26 (100%) achieved ≥50% pain improvement

≥75% improvement was reported in 20% of the neuropathic-pain group and 34% of the inflammatory-pain group at 180 minutes.

General comfort scores increased from 57 → 77 in the neuropathic-pain group and 64 → 79 in the inflammatory-pain group after 24 hours. No treatment-related adverse events were reported.

Reference

Xu F, Treger D, Ma X, et al. Local Injection of a Freshly Manufactured 35 kDa Hyaluronan Fragment Reduces Neuropathic and Inflammatory Pain: A Clinical Study.

European Journal of Inflammation. 2024;22.

DOI: 10.1177/1721727X241258268

B. Chronic Wound-Associated Pain

Chronic wounds with pain >3 months · n=20

• Mean pain NPRS decreased from 4.5 → 2.2 within 24 hours

• This corresponds to approximately 51% mean pain reduction

• By day 10, all participants reported resolution of wound-associated pain

The same study also reported increased granulation tissue, improved peri-wound skin condition, and reduced wound size.

Reference

Treger D, Zhang L, Jia X, et al. A Clinical Study of the Local Injection of a Freshly Manufactured 35 kDa Hyaluronan Fragment for Treating Chronic Wounds.

International Wound Journal. 2024;21(5):e14906.

DOI: 10.1111/iwj.14906

C. Persistent Rheumatoid-Arthritis Pain

Published case report

• Elbow pain: 3 → 0 after one HA35 injection

• Knee pain: 4 → 0 after two injections per knee

• Foot pain: 5 → 2 after repeated local treatment

• Residual foot pain: 2 → 0 after a subsequent 20-day oral HA35 course

Restoration of elbow extension and improved mobility were also reported.

Reference

Liu L, Ma X, Jia X, Hui JH, Hui M. Application of 35 kDa Hyaluronic Acid Fragment in Managing Persistent Localized Pain in Rheumatoid Arthritis: A Case Report.

Clinical Case Reports. 2025;13(4):e70361.

DOI: 10.1002/ccr3.70361

D. Mechanistic Support — TRPV1 & TRPA1

Patch-clamp electrophysiology · n=12 per condition

At 400 μg/mL:

• HA35 inhibited capsaicin-activated TRPV1 currents by 34.46% (P < 0.0001)

• HA35 inhibited AITC-activated TRPA1 currents by 29.27% (P < 0.001)

• No significant effect was observed on TRPV3

These findings provide a molecular link between HA35 and sensory ion-channel pathways involved in pain and itch.

Reference

Ma X, Shofaro J, Jia X, Ma Z, Hui M. The Low Molecular Weight Hyaluronan Fragment HA35 Serves as a Dual Antagonist of Pain-Related TRPV1 and TRPA1 Channels.

Journal of Pharmaceutical Research International. 2025;37(6):38–51.

DOI: 10.9734/jpri/2025/v37i67702

A. Skin Pruritus

10% HA35 gel · Case series · n=5

Topical HA35 was evaluated in five cases of pruritus associated with different skin conditions.

• Complete itch relief was reported within approximately 10 seconds

• Relief was generally maintained for approximately 8–12 hours

• Redness and other local inflammatory signs also improved

• No local irritation or allergic reaction was reported

The published case series reported rapid relief across different causes of pruritus with sustained benefit for approximately 8–12 hours.

Reference

Xu F, Jia X, Hui JH, Gorbunova V, Hui M. Ultra-Rapid Relief of Skin Pruritus by a 10% High-Concentration 35 kDa Hyaluronic Acid Fragment Gel: A Case Series.

Journal of Biosciences and Medicines. 2026;14:395–402.

DOI: 10.4236/jbm.2026.142029

B. Herpes Zoster–Related Pain

10% HA35 topical gel · Case series · n=4

In three patients with acute herpes zoster–associated pain:

• Mean pain NRS decreased by approximately 55% within 2 minutes

• NRS decreased to approximately 1–2 after 20 minutes

• Analgesic effects persisted for approximately 4 hours

In one patient with postherpetic neuralgia, occlusive application extended reported pain relief to more than 8 hours.

Reference

Xu F, Jia X, Hui JH, Gorbunova V, Hui M. Analgesic Effect of High-Concentration 35 kDa Hyaluronic Acid Fragment Gel in Herpes Zoster–Related Pain: A Case Series.

Journal of Dermatological Case Reports. 2026;19(1):5–10.

DOI: 10.61705/jdcr.19.1.2026.5.10