Sermorelin

...........Sermorelin

• Anabolic Agents
• Hormone Replacement Agents
• GEREF SERONO PHARMA

Sermorelin is used in the treatment of children with growth hormone deficiency or growth failure. Geref increases plasma growth hormone (GH) concentration by stimulating the pituitary gland to release GH. Geref is similar to the full-length native hormone (44 residues) in its ability to stimulate GH secretion in humans.
 Sermorelin binds to the growth hormone releasing hormone receptor and mimics native GRF in its ability to stimulate growth hormone secretion.

Cas No.:86168-78-7

Molecular Formula:C149H246N44O42S

Molecular Weight:3357.88

Sermorelin, sometimes called GRF 1-29, is a growth hormone releasing hormone analogue. It is a 29-amino acid polypeptide representing the 1-29 fragment from endogenous human growth hormone releasing hormone, and is thought to be the shortest fully functional fragment of GHRH.^[1] It is used as a test for growth hormone secretion.^[2] It is also used as doping substance in sports.^{[citation needed]}

1. Jump upPrakash A, Goa KL (August 1999). "Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency". BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy 12 (2): 139–57.PMID 18031173.
2. Jump up Pharmacology (Rang, Dale, Ritter & Moore, ISBN 0-443-07145-4, 5:th ed., Churchill Livingstone 2003).

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SERMORELIN ACETATE


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 Sermorelin acetate is the acetate salt of an amidated synthetic 29-amino acid peptide (GRF 1-29 NH 2 ) that corresponds to the amino-terminal segment of the naturally occurring human growth hormone-releasing hormone (GHRH or GRF) consisting of 44 amino acid residues

Sermorelin acetate (sermorelin) is the acetate salt of an amidated synthetic 29- amino acid peptide (GRF 1-29 NH 2 ) that corresponds to the amino-terminal segment of the naturally occurring human growth hormone-releasinghormone (GHRH or GRF) consisting of 44 amino acid residues. The structural formula for sermorelin acetate is:

The free base of sermorelin has the empirical formula C 149 H 246 N 44 O 42 S and a molecular weight of 3,358 daltons.

Sermorelin is a sterile, non-pyrogenic, lyophilized powder intended forsubcutaneous injection after reconstitution with Sodium Chloride Injection, USP. The reconstituted solution has a pH of 5.0 to 5.5.

Sermorelin is available in vials. The quantitative composition per vial is:

0.5 mg vial: Each vial contains 0.5 mg sermorelin (as the acetate) and 5 mg mannitol. The pH is adjusted with dibasic sodium phosphate and monobasic sodium phosphate buffer. 
3.0 mg vial: Each vial contains 3.0 mg sermorelin (as the acetate) and 5 mg mannitol. The pH is adjusted with dibasic sodium phosphate and monobasic sodium phosphate buffer

• In the early 1980's several groups isolated and characterized growth hormone releasing factor (GRF).
• [0003]
  GRF (also called Somatorelin) is a peptide secreted by the hypothalamus, which acts on its receptor and can promote the release of growth hormone (GH) from the anterior pituitary. It exists as 44-, 40-, or 37-amino acid peptide; the 44-amino acid form may be converted physiologically into shorter forms. All three forms are reported to be active, the activity residing mainly in the first 29 amino acid residues. A synthetic peptide corresponding to the 1-29 amino acid sequence of human GRF [hGRF(1-29)], also called Sermorelin, has been prepared by recombinant DNA technology as described in European Patent EP 105 759.
• [0004]
  Sermorelin has been used in the form of acetate for the diagnosis and treatment of growth hormone deficiency.
• [0005]
  GRF has indeed a therapeutic value for the treatment of certain growth hormone related disorders. The use of GRF to stimulate the release of GH is a physiological method in promoting long bone growth or protein anabolism.
• [0006]
  It is well known that the natural form of GRF can suffer from chemical degradation in aqueous solution, primarily of Asn at position 8, which results in reduced biological potency (Friedman, A.R. et al., Int. J. Peptide. Protein Res., 37, 14-20, 1991; Bongers, J., et al., Int. J. Peptide. Protein Res. 39, 364-374, 1992).
• [0007]
  The main hydrolytic reactions occurring in GRF are sensitive to pH and reported to be: rearrangement of Asp³, at pH 4-6.5, cleavage of the Asp³-Ala⁴ bond at pH 2.5-4.5, deamidation and rearrangement of Asn⁸at pH above 7 (Felix A.M. et al., Peptides, editors: Giralt E. and Andreu D., pp 732-733, Escom Publishers 1991). Due to the combined degradation pathways, unstabilized aqueous solutions GRF are most stable in the pH range 4-5. Bongers et al. (Bongers et al., 1992) have shown that the deamidation reaction at Asn⁸ increases rapidly as the pH is raised above pH 3.
• [0008]
  WO 98/53844 describes stable liquid pharmaceutical compositions of hGRF containing nicotinamide and propylene glycol.
• [0009]
  Various workers have made analogues of GRF by substitution of amino acids into the natural GRF sequence to improve the chemical stability (Serono Symposia USA, 1996; Friedman, 1991). While modification can be an effective means to improve the stability and retain bioactivity, it may be undesirable due to altered immunogenicity, which could be a problem for chronic therapies such as growth hormone deficiency.
• [0010]
  According to EP 189 673 and US 4,963,529 (Sumitomo Pharma Inc.) GRF formulations can be prepared by lyophilization and stabilized by human serum albumin or glycine. JP 3083931 and EP 417 930 describe a GRF-containing nasal preparation which is rendered low-irritating to nasal mucosa by adding sodium chloride and/or sugar alcohols, such as mannitol or sorbitol thereto.
• [0011]
  In order that materials like hGRF be provided to health care personnel and patients, these materials must be prepared as pharmaceutical compositions. Such compositions must maintain activity for appropriate periods of time, must be acceptable in their own right to easy and rapid administration to humans, and must be readily manufacturable. In many cases pharmaceutical formulations are provided in frozen or in lyophilized form. In this case, the composition must be thawed or reconstituted prior to use. The frozen or lyophilized form is often used to maintain biochemical integrity and the bioactivity of the medicinal agent contained in the compositions under a wide variety of storage conditions, as it is recognized by those skilled in the art that lyophilized preparations often maintain activity better than their liquid counterparts. Such lyophilized preparations are reconstituted prior to use by the addition of suitable pharmaceutically acceptable diluent(s), such as sterile water for injection or sterile physiological saline solution, and the like.
• [0012]
  Human GRF is found on the market in lyophilized formulations stabilized with mannitol GEREF®, Serono.

 Several years ago scientists and physicians produced the active part of a natural bio-identical releasing factor secreted by the hypothalamus that stimulates the pituitary to secrete growth hormone and called it Sermorelin.  This is now considered by physicians nationwide to be the safest way to improve our quality of life as middle-aged adults become seniors.  It is also much less expensive than growth hormone.

Sermorelin has a safety factor that prevents over-stimulation of the pituitary, another benefit over growth hormone administration.  Since Sermorelin is a releasing factor not a hormone, negative feeback occurs between the hypothalamus and the pituitary keeping the blood levels from ever rising to high in growth hormone.   

Sermorelin treatment requires a laboratory test called IGF-1.  IGF-1  is the active form of growth hormone and doctors use it to get a baseline for the patient to see if they need it and then to see if there is improvement of blood levels while taking Sermorelin.  

Sermorelin is self-administered before bed with a very small diabetic needle because growth hormone is produced by the pituitary between 2 and 4 AM during sleep.