LAVIV - Wrinkles

LAVIV is the first FDA approved cellular therapy to treat the wrinkles of the laugh lines of the smile lines. LAVIV is unlike the facial fillers made of hyaluronic acid or calcium hydroxylapatite. The Miami Institute in Brickell is the first practice in South Florida to start using this novel treatment.The cost for LAVIV treatment is between $3,000 and $3,500.

Proprietary Name: LAVIV®
 

Established (USAN) Name: azficel-T

Indication: LAVIV® is indicated for improvement of the appearance of moderate to severe nasolabial fold wrinkles in adults.

Product description

The active ingredient in azficel-T is autologous cultured fibroblasts. The fibroblasts are cultured, using standard methodologies, from three 3-mm punch biopsies (dermal and epidermal layers) taken from a patient’s post-auricular area. Fibroblasts, due to their proliferative nature, expand more rapidly in culture than the other dermal cell types present, such as keratinocytes. Fibroblasts represent more than 98% of the final product. Following in vitro expansion, the fibroblasts are harvested and quality control tests are performed. The cell suspension is cryopreserved in protein-free media containing DMSO at a defined cell concentration. When required for clinical use, a dose of cells is thawed, washed, formulated to 1.0–2.0 x 107 cells/ml and shipped to the clinical site at 2-8°C by overnight delivery for use within 24 hours of final formulation. The cells are injected intradermally into the nasolabial folds in three separate doses given four to six weeks apart.

No preclinical studies were conducted with azficel-T.

Approximately 1100 subjects received azficel-T at 110 clinics during the 4-year period when the product was marketed in the US (see section 2 Background above). The applicant states that no serious adverse events were reported during this time. Considering this previous commercial experience in humans, and due to the lack of an appropriate animal model for wrinkles, no preclinical studies using azficel-T were necessary.

Efficacy
The co-primary efficacy endpoints for the two pivotal trials were:

Proportion of subjects with at least a two-point improvement, from baseline to six months post-treatment, in wrinkles in both nasolabial folds, using the Evaluator Wrinkle Severity Assessment, a blinded, live assessment using a 6-point ordinal scale (Lemperle scale).

Proportion of subjects with at least a two-point improvement, from baseline to six months post-treatment, in the Subject Wrinkle Assessment, a global 5-point self-assessment of the lower part of the face.

SOURCE: 

Summary Basis for Regulatory Action, Date: June 20, 2011, BLA/ STN#: 125348/0

New Facial Filler Available in Miami NBC Miami, Nov 9, 2011

http://www.nbcmiami.com/news/New-Facial-Filler-now-available-in-Miami-133393038.html

Thunder God Vine

Thunder God Vine has been applied in relieving autoimmune disorders such as rheumatoid arthritis and systemic lupus erythematosus, and for treating cancer. [4]

In the past four decades, the anticancer activities of the Thunder God Vine (Tripterygium wilfordii) extracts from this medicinal herb have attracted intensive attention by researchers worldwide. The diterpenoid epoxide triptolide and the quinone triterpene celastrol are two important bioactive ingredients that show a  divergent therapeutic profile and can perturb multiple signal pathways. [1] Triptolide, a chemical from Thunder God Vine, was found to have anti-cancer activity. In a study, it inhibited proteasomal activity and induced apoptosis in human breast and prostate cancer cells. [2] Celastrol, another chemical originally identified from Thunder of God Vine, it is generally used for the treatment of inflammatory and auto-immune diseases. Celastrol has potential benefits of anti-inflammatory and anti-cancer activities. The anti-inflammatory effects of this triterpene have been demonstrated in animal models of different inflammatory diseases, including arthritis, Alzheimer's disease, asthma, and systemic lupus erythematosus. This triterpene has also been found to inhibit the proliferation of a variety of tumor cells and suppress tumor initiation, promotion and metastasis in various cancer models in vivo. Celastrol's ability to modulate the expression of pro-inflammatory cytokines, MHC II, HO-1, iNOS, NF-κB, Notch-1, AKT/mTOR, CXCR4, TRAIL receptors DR4 and DR5, CHOP, JNK, VEGF, adhesion molecules, proteasome activity, topoisomerase II, potassium channels, and heat shock response has been reported. [3,5,7-9]

[1] Liu Z, et al, The main anticancer bullets of the Chinese medicinal herb, thunder god vine. Molecules. 2011 Jun 23;16(6):5283-97. [2] Lu L, et al, Inhibition of tumor cellular proteasome activity by triptolide extracted from the Chinese medicinal plant 'thunder god vine'. Anticancer Res. 2011 Jan;31(1):1-10. [3] Kannaiyan R, et al, Molecular targets of celastrol derived from Thunder of God Vine: potential role in the treatment of inflammatory disorders and cancer. Cancer Lett. 2011 Apr 1;303(1):9-20. [4] Law SK, et al, Molecular analyses of the Chinese herb Leigongteng (Tripterygium wilfordii Hook.f.). Phytochemistry. 2011 Jan;72(1):21-6. [5] Salminen A, et al, Celastrol: Molecular targets of Thunder God Vine. Biochem Biophys Res Commun. 2010 Apr 9;394(3):439-42. [7] Pang X, et al, Celastrol suppresses angiogenesis-mediated tumor growth through inhibition of AKT/mammalian target of rapamycin pathway. Cancer Res. 2010 Mar 1;70(5):1951-9. [8] Davenport A, et al, Celastrol and an EGCG pro-drug exhibit potent chemosensitizing activity in human leukemia cells. Int J Mol Med. 2010 Mar;25(3):465-70. [9] Chen M, et al, Celastrol synergistically enhances temozolomide cytotoxicity in melanoma cells. Mol Cancer Res. 2009 Dec;7(12):1946-53.

Dan Shen Herb - Drug Interaction

Herbal medicines are often administered in combination with drugs, raising the potential of herb-drug interactions. Cases have been published reporting enhanced anticoagulation and bleeding when patients on long-term warfarin therapy also took dan shen herb. [1] Interactions between herbal medicines and drugs can occur and may lead to serious clinical consequences. There are other theoretical interactions indicated by preclinical data. Both pharmacokinetic and/or pharmacodynamic mechanisms may also play a role in these interactions, dependent on the nature of the drug substance.

Dan Shen herb extract is widely used for the treatment and prevention of coronary heart disease and some other diseases. Dan Shen herb extract and theophylline are prescribed together to treat patients with asthma in some areas. In human, theophylline with low therapeutic index is mainly metabolized by CYP1A2. In vitro findings have shown that human CYP1A2 is inhibited by the ethyl acetate extract of Dan Shen Herb and Dan Shen pharmaceutical product. Thus, one may expect that there may be drug interactions between Dan Shen extract and theophylline (CYP1A2 substrate). However, it was found that long-term oral intake of Dan Shen Herb extract does not change the basic pharmacokinetic parameters of theophylline in healthy subjects. Dose adjustment of theophylline thus may not be necessary in patients receiving concomitant therapy with Dan Shen extract. [2]

Dan Shan Herb contains protocatechualdehyde, salvianolic acid B, tanshinone II(A), cryptotanshinone, etc. Some Dan Shen components in the hydrophilic extract depress the absorption of the protocatechualdehyde in rats, on the contrary, enhance the absorption of the salvianolic acid B and depress its elimination rate. The concomitant components in the lipophilic extract might enhance the absorption of cryptotanshinone and its distribution from the centre compartment to the peripheral compartment, and the metabolism to tanshinone II(A). [3]

Thus, the 'concomitant components' in the extract of Chinese material medica had significant effect on the pharmacokinetics of its 'active components'. It can not only be rival, synergic, but also have the effects on metabolism. Therefore the traditional Chinese medicine was a complicated system, It should be taken a scientific and dialectic view in the research and development processes. [3]

Strong protein (albumin) binding of Dan Shen (50-70%) in serum was observed. Salicylate, a chemical, is also strongly bound to albumin; it is also a widely used over-the-counter medicine in the U.S., we studied Danshen-salicylate interaction in vitro. No significant change in free Dan shen concentrations was observed when salicylate concentrations were subtherapeutic (< or = 100 microg/mL). However, with therapeutic concentrations of salicylate (> or = 150 microg/mL), the free Dan Shen concentrations significantly decreased. On the other hand, Dan Shen potentially displaced salicylate from protein binding, thereby increasing the free salicylate concentration.

[1] Hu Z, et al, Herb-drug interactions: a literature review. Drugs. 2005;65(9):1239-82. [2] Qiu F, Effect of danshen extract on pharmacokinetics of theophylline in healthy volunteers.Br J Clin Pharmacol. 2008 Feb;65(2):270-4. [3] Song M, et al, Pharmacokinetic interactions between the main components in the extracts of Salvia miltiorrhiza Bge. in rat Yao Xue Xue Bao. 2007 Mar;42(3):301-7. [4] Gupta D, et al, Drug-herb interactions: unexpected suppression of free Danshen concentrations by salicylate. J Clin Lab Anal. 2002;16(6):290-4.