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Immunodeficiency is one of the biggest challenges in the field of medicine.

Disorders of the immune system can either be inherited with poor immune system since birth (called primary immune deficiency), weak immune system caused by another disease (called acquired immunodeficiency) or suffer from a condition where the immune system works against the body (called autoimmune disease) (1).

While there are various medicines and drug therapies being prescribed to control the immune disorders, the major drawback is that there are severe adverse events caused upon their administration. This is where the peptides come into play.

Synthetic peptides are analogous to the naturally occurring amino acids and hence are highly biocompatible, causing minimal side effects.

Talking about immunodeficiency, one of the peptides to fight this condition is Thymalin.

What is Thymalin Peptide

Thymalin is a polypeptide isolated from the thymus gland that helps to regulate the immune system of the body (2).

Thymus in Greek means “soul” and is likely named so as it helps house the human soul. A variety of animal species possess this gland, signaling that the organ is ancient and extremely vital. Also, various discoveries have confirmed that the thymus gland helps manage the body's immune system, and thereby one’s quality of life (3). Thymus gland secretes various proteins, namely thymic peptides, which help regulate the immune system. Thymalin is one such thymic peptide complex, and it helps manage and overcome immune exhaustion.

History

Natural thymic peptides such as Thymalin were first isolated from a calf thymus gland with the help of a mild acid extraction process. Upon further isolation studies, the immunomodulatory molecule composed by Thymalin (L-Glu-L-Trp) was discovered. This dipeptide molecule in Thymalin plays a vital role in the peptide mechanism (4).

Studies have demonstrated that Thymalin, which is a natural polypeptide, is primarily found in the young epidermal cells of the thymus gland. With increasing age, the levels of Thymalin decrease; and by the age of 70 years, the Thymalin containing cells are thinned out and non-uniform in nature (5). This is why Thymalin, and derived synthetic peptides, become vital not only for immunodeficient patients, but also for aged people fighting other ailments.

How does Thymalin work?

A study was conducted to understand the functioning on both natural and synthetic thymic peptides (6). The compounds studied were Thymalin (natural polypeptide), Thymogen (synthetic peptide) and Vilon (its derived dipeptide).

The study determined that all the peptides mainly function by stimulating thymic functions i.e., differentiation of T-cells, induced changes in the nucleotides and cytokine cells and secretion of lymphocytes. This improved the body’s immune responses towards fighting the antigens and protecting the body functioning.

The other significant discovery made during this study was that the natural peptide, i.e Thymalin, stimulated the antioxidant responses, whereas the two synthetic analogues did not alter these responses. This indicated that the natural peptides also regulate the inflammatory responses of the cytokine cells, in addition to above mentioned functions

Benefits and Uses of Thymalin

As previously mentioned, the main use of Thymalin is that it helps regulate the body’s immune system.

Given this key advantage of the peptide, Thymalin is used in the treatment of the following:

  • Acute respiratory syndrome
  • Chronic obstructive bronchitis – and hence, being researched as a prospective COVID-19 treatment agent
  • Goiter – abnormal enlargement of the thyroid gland
  • Cancer, lympholeukemia
  • Herpes
  • Reduces aging effects

It should be noted that this is not an exhaustive list and Thymalin is rigorously being studied to understand its full potency and use to treat various other immunodeficiency diseases.

Thymalin Research and Clinical Studies

Thymalin Anti-aging and Carcinogenesis Inhibition

In this study (7), 76 female rats of five months of age were selected. The main aim of this study was to determine the effects of Thymalin on the tumor development and thereby the survival rates and life span extension.

The rats were divided into two groups, where 32 rats were injected subcutaneously with 0.2ml dose of saline, and the remaining rats were treated with 5 microg of Thymalin dissolved in 0.2ml saline via the same route. The doses were administered 5 times a week for one year. All rats were monitored for mortality rates and development of tumors throughout the one-year period.

The results demonstrated that the average lifespan in the control treated group was 949 days whereas in the peptide treated group was 1048 days. The aging rate also decreased, as it was 0.0071 days in the control group, while it was 0.0041 in the peptide treated group. What's more, the tumor incidence decreased by 1.5 times as compared to the control group.

This study demonstrated that Thymalin inhibits tumor formation in the body, while also increasing the average life span and slowing down the aging process.

Human Herpes Viral Infections and Thymalin

In this study (8), 50 females suffering from human alpha herpesvirus 1 (HHV 1) and healthy subjects were enrolled. All the volunteers were treated with the peptide for a period of 2 months. After the treatment, peripheral blood cell tissues were collected from the volunteers and examined to monitor the cytokine levels upon peptide treatment.

Upon analysis, it was determined that compared to the healthy volunteers, the cytokine levels were elevated in a higher proportion in the patients. The levels of cytokines CD4+ and CD8+ were more in the patients as compared to the other volunteers. Also, after the two-month treatment period, there was no reactivation of the HHV 1 virus in the patients.

This study determined that reactivation of HHV 1, which is linked to the suppression of the immune system, was reversed on the Thymic peptide treatment.

Diffuse Toxic Goiter Treatment with Thymalin

In this study (9), 104 patients with mild Diffuse Toxic Goiter (DTG) were enrolled, and their levels of medium weight molecular peptides and lipid oxidation rates were monitored. The main aim of this study was to establish the efficiency of Thymalin in treating DTG.

The patients were divided into five groups where group one was treated with mercazolyl, group two was treated with lithium salt, group three with mercazolyl and Thymalin, group four with mercazolyl and piracetam, and group five with mercazolyl, piracetam and Thymalin.

After the treatment, it was determined that the fifth group treated with mercazolyl, piracetam and Thymalin showed the most beneficial results, proving that Thymalin can potentially be treated to manage DTG.

COVID-19 Studies

There is no clinical evidence currently available to affirm the use of Thymalin for the treatment of COVID-19. This study is highly theoretical, which suggests how Thymalin appears to be a promising candidate to treat the world pandemic, COVID-19.

COVID-19 is caused by the SARS-CoV-2 virus, which decreases the level of lymphocytes CD28+, CD4+ and CD8+. This event suppresses the body’s immune system, leading to acute respiratory distress and possible organ failure (10,11).

This theory (11) is based on the effect of Thymalin in hematopoietic stem cell (HSC) differentiation, and the subsequent effects on CD28 cell expression. Upon Thymalin administration, it was noted that it increased the rate of HSC differentiation by up to 3 times and thereby reduced the levels of stem cell markers CD44 and molecules CD117, while increasing the CD28 cell expression by 7 times.

This indicated that Thymalin stimulated CD117 differentiation, causing the cells to mature to CD28 lymphocytes.

Thus, Thymalin possessed immunomodulatory and immunoprotective properties which could help establish optimal levels of lymphocytes in COVID-19 patients and restore their immunity.

Combined Treatment in Chronic Lympholeukemia

In this study (12), patients with chronic lymphoid leukemia were enrolled in the inclusion study composed of specific and nonspecific immune correction treatment, namely Thymalin treatment and plasmapheresis, respectively.

Compared to the sole treatment with chemotherapeutic agents, this combined treatment, that was used for the first time, resulted in improved physiological functioning of the body within a short period of time.

Combined Treatment to Study the Geroprotective Properties of Thymalin

In this study (13), the geroprotective properties of Thymalin (thymic peptide) and Epithalamin (pineal peptide) were studied on 266 elderly patients for a period of 6 to 8 years. The patients were treated with the peptides for the first 2 to 3 years and were then monitored on a regular basis.

The patients were treated into several groups: group I was administered with Thymalin, group II with Epithalamin, group III with both peptides and a separate group where patients were administered with both peptides at a different dosage rate. The peptides were administered annually for 6 years.

The studies demonstrated that basic human functions improved significantly upon treatment with both the peptides, including cardiovascular, neurological, immunological functions and improved rates of metabolism and hemostasis. As a result of this distinct improvement, the mortality rate decreased by 2.1 times in Thymalin treated patients, decreased by 1.8 times in Epithalamin treated patients and decreased by 2.5 times in combination therapy. The patients who were annually treated with the combined peptides showed an improvement in the mortality rate by 4 times than usual.

Hence, the studies determined the geroprotective peptides of Thymalin, and its ability to increase the longevity of human life.

Thymalin Side Effects

As mentioned earlier, Thymalin is a natural polypeptide and hence is highly compatible with the human body. In the study (13), Thymalin was administered in aged people for 6 to 8 years with no reported adverse events. This suggests Thymalin is highly safe and otherwise causes no adverse events in the body.

The only possible syndrome that may occur with thymus peptide extracts, including Thymalin, may be ‘mad cow disease’. Since Thymalin is extracted from bovine thymus gland, there are chances that the peptide may be contaminated with any diseased parts of the animal, and hence may cause this adverse event. However, there are no reported cases of this event and therefore the probability of this event is negligible (14).

Precautions

Thymalin should not be used by patients who are undergoing treatment to weaken their immune system, for instance in the case of organ transplants. Both the treatments are highly contradicting and hence, not recommended (14).

Possible Drug Interactions with Thymalin

Immunosuppressants, as the name suggests, weaken the immune system. Thymalin should not be co-administered while on immunosuppressant therapy. This is because Thymalin is extracted from animals, which causes a concern that the peptide may be cross-contaminated with animal parts and may cause serious infections as these will not be well tolerated by the body (14).

Thymalin Peptide Profile

Based on this 1980 study (15), a single dose of 100 microg Thymalin was administered in rats via subcutaneous route of administration which resulted in almost 55% decrease in the cysticerci infection. Based on this and above-mentioned studies, there is reasonable evidence suggesting that Thymalin is usually administered via subcutaneous route at a single dose per day.

Furthermore, based on the 8-year long study (13) of Thymalin treatment, it can be affirmed that Thymalin is highly safe in humans producing no reported side effects in people.

Thymalin vs Thymulin

While there is some online info claiming that the two peptides are interchangeable, that is not the case.

Thymulin is a biologically active nonapeptide, which possesses hormonal properties, and is synthesized by the thymic epithelial cells. Also known as serum thymic factor (18), its biological activity is dependent on the presence of zinc metal in the molecule. Thymulin is a natural hormone that stimulates T-cell differentiation and enhances the T-cell functions in both normal recipients and patients with a partially deficient thymus (17).

Difference between Thymalin and Thymulin

While both Thymalin and Thymulin are naturally occurring thymic factors, their mode of action is different, where Thymalin is a polypeptide that regulates the thymic functions and ensures the body immunity is at optimal level, and Thymulin is a zinc dependent nonapeptide hormone that enhances the thymic functions to fight any T-cell suppression.

Summary

Thymalin is a potent natural polypeptide secreted by the thymus gland in the body and helps regulate the immune system of the body.

Thymalin, which was first extracted from the calf thymus gland, produces effects similar to the thymic peptides and regulate the levels of T-cell differentiation, induces lymphocyte and cytokine formation, and thereby stimulates the immune system.

Thymalin possesses immunoprotective, immunomodulatory and geroprotective properties. It helps maintain optimal levels of body immunity and reverse any weakened immune response. Being geroprotective in nature, Thymalin improves the functioning of the vital body systems and extends the average lifespan of humans.
Given that Thymalin regulates the levels of lymphocytes in the body, including CD28 cells, it makes Thymalin a strong candidate for the treatment of COVID-19.

Interestingly, in a recent case study in Russia (16), Thymalin was administered in a 60-year-old patient suffering from COVID-19 like symptoms. The patient was diagnosed with acute respiratory failure and flu-like symptoms. The patient was administered with 10mg Thymalin via subcutaneous route for 7 days, along with other medications administered earlier to the patient. After the course of Thymalin treatment, the patient’s body temperature decreased to normal and there was an improvement in the respiratory functions.

While the case study shows promising results, Thymalin is further being studied by the scientists to collect sufficient data to establish Thymalin treatment in controlling COVID-19 pandemic.

References:

1. Disorders of the Immune system. https://www.hopkinsmedicine.org/health/conditions-and-diseases/disorders-of-the-immune-system

2. Khavinson VK, Linkova NS, Kvetnoy IM, Polyakova VO, Drobintseva AO, Kvetnaia TV, Ivko OM. Thymalin: Activation of Differentiation of Human Hematopoietic Stem Cells. Bull Exp Biol Med. 2020 Nov;170(1):118-122. doi: 10.1007/s10517-020-05016-z. Epub 2020 Nov 25. https://pubmed.ncbi.nlm.nih.gov/33237528/

3. Remien K, Jan A. Anatomy, Head and Neck, Thymus. [Updated 2021 Feb 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK539748/

4. Morozov VG, Khavinson VK. Natural and synthetic thymic peptides as therapeutics for immune dysfunction. Int J Immunopharmacol. 1997 Sep-Oct;19(9-10):501-5. doi: 10.1016/s0192-0561(97)00058-1. https://pubmed.ncbi.nlm.nih.gov/9637345/

5. Khlystova, Z.S., Kalinina, I.I., Shmeleva, S.P. et al. Age-Related Changes of Thymalin Content in Human Epidermis. Bulletin of Experimental Biology and Medicine 133, 620–622 (2002). https://doi.org/10.1023/A:1020214816056

6. V.G. Morozov, V.Kh. Khavinson, Natural and synthetic thymic peptides as therapeutics for immune dysfunction, International Journal of Immunopharmacology, Volume 19, Issues 9–10, 1997, Pages 501-505. https://www.sciencedirect.com/science/article/abs/pii/S0192056197000581

7. Anisimov VN, Khavinson VK, Morozov VG. Immunomodulatory synthetic dipeptide L-Glu-L-Trp slows down aging and inhibits spontaneous carcinogenesis in rats. Biogerontology. 2000;1(1):55-9. https://pubmed.ncbi.nlm.nih.gov/11707921/

8. Hymos A, Grywalska E, Klatka J, Klatka M, Korona-Głowniak I, Roliński J. ThymicPeptides Reverse Immune Exhaustion in Patients with Reactivated Human Alphaherpesvirus1 Infections. Int J Mol Sci. 2020 Mar 30;21(7):2379. https://pubmed.ncbi.nlm.nih.gov/32235584/

9. Iangolenko VV. The effect of combined therapy with the use of thymalin and piracetam on the level of middle-molecule peptides in the blood and on the lipid peroxidation activity in patients with diffuse toxic goiter. Ter Arkh. 1991;63(10):60-3. Russian. https://pubmed.ncbi.nlm.nih.gov/1725225/

10. Khavinson, V., Linkova, N., Dyatlova, A., Kuznik, B., & Umnov, R. (2020). Peptides: Prospects for Use in the Treatment of COVID-19. Molecules (Basel, Switzerland), 25(19), 4389. https://doi.org/10.3390/molecules25194389

11. Khavinson, V. K., Linkova, N. S., Kvetnoy, I. M., Polyakova, V. O., Drobintseva, A. O., Kvetnaia, T. V., & Ivko, O. M. (2020). Thymalin: Activation of Differentiation of Human Hematopoietic Stem Cells. Bulletin of experimental biology and medicine, 170(1), 118–122. https://doi.org/10.1007/s10517-020-05016-z

12. Tretiak NN, Babenko TF, Gaĭdukova SN, Zverkova AS, The efficacy of using thymalin and plasmapheresis in the combined treatment of patients with chronic lympholeukemia. Lik Sprava. 1998 Mar-Apr;(2):93-6. Russian. https://pubmed.ncbi.nlm.nih.gov/9670669/

13. Khavinson VKh, Morozov VG. Peptides of pineal gland and thymus prolong human life. Neuro Endocrinol Lett. 2003 Jun-Aug;24(3-4):233-40. PMID: 14523363. https://pubmed.ncbi.nlm.nih.gov/14523363/

14. Thymus extract, side effects. https://www.webmd.com/vitamins/ai/ingredientmono-1009/thymus-extract

15. Hermánek J, Prokopic J. Influence of thymic preparations on the result of experimental infection with Taenia crassiceps (Zeder, 1800) in ICR mice. Folia Parasitol (Praha). 1989;36(4):331-40. https://pubmed.ncbi.nlm.nih.gov/2488049/

16. Vladimir Khavinson, Natalia Linkova, Anastasiia Dyatlova, Boris Kuznik 5 and Roman Umnov. Peptides: Prospects for Use in the Treatment of COVID-19. 19 August 2020, published 24 September 2020. https://www.mdpi.com/1420-3049/25/19/4389

17. Bach JF, Dardenne M. Thymulin, a zinc-dependent hormone. Med Oncol Tumor Pharmacother. 1989;6(1):25-9. doi: 10.1007/BF02985220. PMID: 2657247. https://pubmed.ncbi.nlm.nih.gov/2657247/

18. National Center for Biotechnology Information. "PubChem Compound Summary for CID 3085284, Nonathymulin" PubChem, https://pubchem.ncbi.nlm.nih.gov/compound/Nonathymulin


 

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