Evaluation of Safe and Effectiveness of an Injectable ...

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

If you want to learn more, please visit our website.

Studies have shown that the second-generation solution containing sodium deoxycholate 1.25% is effective and safe to treat different localized fat deposits. The high degree of effectiveness shown in the study was not associated with a lesser degree of handling because, at the doses indicated and with the use of intralipotherapy, the occurrence of adverse events was minimal.

Two hundred twenty-one patients treated in 273 cases of different localized fat deposits. One hundred eighty-five patients who could be assessed for final results gave the effectiveness of the treatment an average score of 7.4. The failure percentage of the treatment was 3.8%. The medical evaluation showed treatment success in 93.5% of cases. Adverse events can be divided into 2 groups: minor adverse events, which are very frequent and major ones, which are extremely rare. For both groups, the adverse events can be ascribed to localized problems in the treatment area.

The effectiveness and safety of DB125 solution have been assessed with a multicentre observational prospective study carried out between February and October 2017. The 221 selected patients presented with various forms and degrees of localized fat in several areas. Intralipotherapy treatments were performed 6 weeks apart and until the clinical result was obtained. Aesthetic outcomes were evaluated by the authors using preoperative and postoperative photographic documentation and by the patients with their level of satisfaction by filling out an anonymous form. Major adverse events were reported by each doctor who performed the treatment.

The use of deoxycholic acid to reduce localized fat deposits is a procedure that has been in use for about 30 years. Its effectiveness as treatment is due to emulsification of phospholipids and therefore, solubilization of the biological membranes with resulting fat necrosis. The purpose of the study was to assess the effectiveness and the safety of an injectable solution containing sodium deoxycholtate 1.25% (DB125), used as intralipotherapy.

The purpose of the study was to assess the effectiveness and the safety of an injectable solution containing sodium deoxycholate 1.25% for the treatment of localized fat deposits on the body (125 mg/10 ml - DB125), second generation (free from phosphatidylcholine), used with intralipotherapy.

The use of solutions containing sodium deoxycholate to reduce unwanted fatty deposits is a procedure that has been used in aesthetic medicine for about 30 years. 1 – 4 Over the years, there have been numerous adipocytic solutions characterized by different chemical compounds but which however show deoxycholic acid as the sole agent able to bring about effective treatment 5 – 7 by means of cell damage through the emulsification of the phospholipids and therefore, solubilization of biological membranes (citoplasmic, nuclear, of the organelles) 8 with resulting unprogrammed cell death (adipocyte necrosis). 9 From the first solutions referring to the so-called Natterman formula, 10 containing also phosphatidylcholine, incorrectly considered as the active ingredient in reducing fat deposits under the skin, 5 – 7 we have passed to those of the second generation, which are more effective, where phosphatidylcholine has been eliminated and the concentration of deoxycholate acid has been reduced to mitigate the aggressiveness of its action 11 , 12 (Table ). Today, it is universally accepted that second-generation solutions are far more effective but more aggressive. 13 , 14

Aesthetic outcomes were evaluated by the authors using preoperative and postoperative photographic documentation. In some cases, pre- and postultrasound and/or centimetric evaluations were made. In patients who had been treated in different areas simultaneously, each area was evaluated independently. Each case was assessed by 2 doctors who did not perform the treatment; they did not know the characteristics of the treatment (number of sessions, the quantity infiltrated, and the doctor who performed the treatment). The question put to the 2 doctors was divided into 2 categories: liporeduction change—significant or nonsignificant. The outcome was considered positive only if observed by both doctors. The patients also evaluated the results: their level of satisfaction was rated and the occurrence of minor adverse events (that were very frequent) was evaluated by filling out an anonymous form in the waiting room and given to nonmedical personnel (the results were rated from 0 to 10, where 0 is “no result at all” and 10 is “the best result achievable”). Major adverse events were reported by each doctor who performed the treatment. The postoperative evaluations were not performed before 2 months after the last treatment. Follow-up ranged from a minimum of 2 months to a maximum of 6. Aesthetic outcome was evaluated only in patients who completed the right follow-up. Patients evaluated with variations of 4% of initial body weight were considered in this study from the safety viewpoint but not in terms of results.

- From the access point that was marked, the intralipotherapy needle (a long, 23-gauge × 10 cm needle, very similar to the needles used for spinal anesthesia) is inserted into the subcutaneous fat parallel to the cutaneous surface, avoiding contact with the skin and muscle. The total amount of the device previously calculated to be used is distributed using a retrograde release and a fan technique, releasing 0.2–0.4 mL of product during each passage. The fan technique consists of an advancing and retracting movement of the needle, very similar to that used with liposuction.The panniculus adiposus is a 3-dimensional structure with an extension and a thickness that varies. It is well represented centrally (core area) and less graded in the surrounding areas. The aim of the intralipotherapy is to treat localized fat throughout its thickness and extension, releasing the lipoclasic solution in a parceled, controlled manner.

- In a decubitus position, the best position according to the area to be treated, infiltration of the device is performed after first disinfecting the area to be treated.

- Marking the treatment area and access points (2–3 per area, opposing if possible) when the patient is in an orthostatic position and the calculation for the quantity of the device required.

After the treatment, the use of contenitive elastic sheaths or a pressure bandage was compulsory for the first 72 hours (24 hours per day) and highly recommended during the first week post. These, in addition to reducing the initial pain, which is typical during the first 12 to 24 hours, also reduce edema, the risk of increasing skin laxity and in general, the posttreatment phase. Lymphatic drainage or pressure therapies were also advised to reduce the postoperative phase and accelerate a full recovery (2 sessions per week for 2–3 weeks posttreatment starting from the third day after the treatment). No other therapies or techniques were allowed in the treated area throughout the study. Pain killers were allowed although generally not necessary.

The authors treated 221 patients in different areas of the body in the way and according to the dosages described as follows.

They did not present with any exclusion criteria for the treatment: psychological (indecisive or immature personalities, anxiety, dismorphophobia, with fictitious disorders, or family members disapproving the treatment), minors, over 60 years old, pregnancy, women who are lactating, obesity, severe allergic reactions, known allergies to the device or to the local anesthetics, severe autoimmune diseases, acute infections in progress, immunosuppressive diseases with weakened immune systems, organ diseases uncompensated, with functional deficits or in acute phase (diabetes, kidney failure, liver disease, severe dyslipidemia, dysthyroidism, and so on), using anticoagulants, with hemorrhagic diathesis or platelet disease.

Adverse events caused by the use of deoxycholic acid can be divided into 2 groups: minor adverse events, which are very frequent and major ones, which are extremely rare. 15 , 17 – 20 With the exception of allergic reactions (which never occurred in this study), for both groups, the adverse events can be ascribed to localized problems during treatment. 21 – 25 Minor adverse events were oedema in the first 72 hours (78%), mild pain lasting more than 12 hours (60%), bruising (41%), warmth (39%), numbness (30%), erythema (28%), and nodules lasting less than 1 month (14 %). Major adverse events were prolonged oedema lasting more than 72 hours (18 cases 2,1%), permanent nodules lasting more than 1 month (8 cases, 0.9%), skin irregularities (4 cases, 0.5%), skin necrosis (1 case, 0.01%), hyperpigmentation (0), permanent paresthesia/dysesthesia (0) and alopecia (0).

One hundred eighty-five patients who could be assessed for final results, for a total of 232 cases of localized fat, gave the effectiveness of the treatment an average score of 7.4 (7.51 in men with 90 cases of localized fat treated and 7.33 in women with 142 cases of localized fat deposits treated). The greatest successes were the flanks, abdomen, and inner knee, while the least successful were the inner thigh and arms (Figs. –4). The percentage of treatment failures, assessed with a score of less than 6, was 3.8% (9 cases of localized fat). The medical evaluation showed therapeutic success in 217 (93.5%) of the 232 cases of localized fat. The failures were 5 inner thighs, 4 saddlebags, 2 arms, 2 abdomens with build up of fat above the navel, 2 inner knees. No significant difference was evaluated when comparing the results in males and females in the same area. However, irrespective of sex, localized android fat-type (abdomen and flanks) showed increased responsiveness to treatment over the gynoid-type liporeductive adiposity (saddlebag thighs, inner thighs, and inner knee).

The study treated 221 patients, 159 women, and 62 men, for a total of 273 body areas (57 abdomen, 51 flanks, 42 saddlebag thighs, 38 inner knee, 29 inner thighs, 26 back rolls, 17 arm, 8 pseudogynecomastia, 5 buffalo hump) and 857 infiltration sessions (average 3.14 per anatomical area). Thirty-six patients were assessed from a safety point of view and not in terms of effectiveness, because their weight variation was above 4%.

DISCUSSION

The results of the study are encouraging because they have shown a therapeutic success from both the viewpoint of specialist medical assessment and from the personal, subjective view of the patients treated. This success did not show any significant differences between sexes and age ranges. Even the different areas on the body did not show significant differences in terms of results, even if, however, the primary-gynoid deposits required more treatment sessions compared with the secondary-android ones. This is due to the fact that localized fat deposits on the body have different histological characteristics: the primary deposits are prevalently hyperplastic, whereas the secondary ones are hypertrophic.26

From a safety viewpoint, the study showed that DB125 used in intralipotherapy and at the correct dosage, is safe. This is due to the fact that:

• 27 Deoxycholic acid is a nonselective surfactant, meaning it causes damage to the cell through emulsification where it is injected. However, it has been shown that it is more effective if there is a lower protein percentage in the cell: this means that mature adipocytes are extremely more vulnerable to deoxycholic acid (because the protein content is less than 5%) than other cell lines with a higher concentration of protein (for example, the myocyte has a protein percentage of more than 95%).

  - Deoxycholic acid has a partial selectivity toward mature adipocytes.Deoxycholic acid is a nonselective surfactant, meaning it causes damage to the cell through emulsification where it is injected. However, it has been shown that it is more effective if there is a lower protein percentage in the cell: this means that mature adipocytes are extremely more vulnerable to deoxycholic acid (because the protein content is less than 5%) than other cell lines with a higher concentration of protein (for example, the myocyte has a protein percentage of more than 95%).

• 11 Making only 1–3 access points in the area to be treated (reducing the risk of DB125 contact with epidermis and derma), the possibility to modulate the depth at which to release the deoxycholic acid (therefore, never on the surface, that is, on the subdermal layer), fragmentary retrograde release (never in bolus) make it possible to correctly distribute the solution through the fatty layer and avoiding surface and deep structures.

  - Administration using intralipotherapy makes it possible to used the deoxycholate sodium correctly.Making only 1–3 access points in the area to be treated (reducing the risk of DB125 contact with epidermis and derma), the possibility to modulate the depth at which to release the deoxycholic acid (therefore, never on the surface, that is, on the subdermal layer), fragmentary retrograde release (never in bolus) make it possible to correctly distribute the solution through the fatty layer and avoiding surface and deep structures.

The study showed a very low incidence of major adverse events. Alopecia, nerve injury, hyperpigmentation never occurred during this study. Nevertheless, it is good to stress that a larger number of cases would have certainly been more significant. The only case of skin necrosis that occurred in this study, limited to a small area of around 1 cm2, should be ascribed to the incorrect execution of the technique, as confirmed by the medical operator who released an excessive amount, too close to the surface (immediately under the derma) DC125 on the site of necrosis. This stresses the importance of using an appropriate technique, educational training, and to have suitable experience.28 Prolonged oedema and permanent nodules are closely tied to the anatomical areas being treated: the almost complete totality of cases occurred on treatment of the knee and abdomen. Two factors, such as the force of gravity and the lymphatic system probably play an important role in these areas.

In Italy, BD125 is classified as a nonprepackaged industrial galenic based on Legislative Decree no. 21929 of 24 April 2006 “Implementation of the directive 2001/83/EC30 pursuant to a community code concerning medicines for human use, and directive 2003/94/EC”.31 BD125 is only produced on the presentation of a specific request from a physician who undertakes to use it on his or her own patients or patients in the facility in which s/he works, under his/her direct responsibility and compliant with the current standards. A written request from a physician exonerates these medicines from the issue of a specific, preventive marketing authorization by the pharmaceutical company manufacturing it, but which nonetheless must hold a Manufacturing Permit for the pharmaceutical form requested. For the purposes of the prescription, the provisions envisaged for medicines listed in article 5 of legal decree no. 23 of 17 February 1998, 23, converted, through amendment by law no. 94 of 8 April 1998.32

Bile acid

Chemical compound

Deoxycholic acid is a bile acid. Deoxycholic acid is one of the secondary bile acids, which are metabolic byproducts of intestinal bacteria. The two primary bile acids secreted by the liver are cholic acid and chenodeoxycholic acid. Bacteria metabolize chenodeoxycholic acid into the secondary bile acid lithocholic acid, and they metabolize cholic acid into deoxycholic acid. There are additional secondary bile acids, such as ursodeoxycholic acid. Deoxycholic acid is soluble in alcohol and acetic acid. When pure, it exists in a white to off-white crystalline powder form.

Deoxycholic acid is available as a generic medication in the United States as of April 2021, sold under the brand name Kybella among others.[8]

Applications

[

edit

]

Deoxycholic acid has been used since its discovery in various fields of human medicine. In the human body deoxycholic acid is used in the emulsification of fats for absorption in the intestine. It has, in some countries (including Switzerland) been licensed as an emulsifier in food industry,[9] but it is no longer common. Outside the body it is used in experimental basis of cholagogues and is also in use to prevent and dissolve gallstones.[citation needed]

In research deoxycholic acid is used as a mild detergent for the isolation of membrane associated proteins. The critical micelle concentration for deoxycholic acid is approximately 2.4–4 mM.[10]

Sodium deoxycholate, the sodium salt of deoxycholic acid, is often used as a biological detergent to lyse cells and solubilise cellular and membrane components.[11] Sodium deoxycholate mixed with phosphatidylcholine, is used in mesotherapy injections to produce lipolysis, and has been used as an alternative to surgical excision in the treatment of lipomas.[12]

Deoxycholates and bile acid derivatives in general are actively being studied as structures for incorporation in nanotechnology.[13] They also have found application in microlithography as photoresistant components.[14]

Featured content:
Suncore Foods Passion Fruit Powder & Seeds
What Makes Low Price Bulk Beet Root Juice Powder So Popular?

Goto chenlv to know more.

In the United States, deoxycholic acid, under the brand name Kybella, is approved by the Food and Drug Administration for reducing moderate-to-severe fat below the chin.[6][15] When injected into submental fat, deoxycholic acid helps destroy (adipocytes) fat cells, which are metabolized by the body over the course of several months.[15] Kybella is produced by Kythera Biopharmaceuticals.[16][17]

Research in immunology

[

edit

]

Its function as a detergent and isolating agent for membrane proteins also suits it for production of outer membrane protein (OMP) vaccines such as MenB, a Norwegian vaccine developed in the early 1990s.[18] The MeNZB vaccine was produced using the same method.[19]

Deoxycholic acid binds and activates the membrane enzyme NAPE-PLD, which catalyzes the release of the endogenous cannabinoid anandamide and other N-acylethanolamines. These bioactive signaling molecules play important roles in several physiological pathways including stress and pain response, appetite, and lifespan.[20]

Some publications point towards the effect of deoxycholic acid as an immunostimulant[21][22] of the innate immune system, activating its main actors, the macrophages. According to these publications, a sufficient amount of deoxycholic acid in the human body would correspond with a good immune reaction of the non-specific immune system. Clinical studies conducted in the 1970s and 1980s confirm the expectation that deoxycholic acid is involved in the natural healing processes of local inflammations,[23][24] different types of herpes,[25][26] and possibly cancer.[27][28]

Research in cancer

[

edit

]

Deoxycholate and other secondary bile acids cause DNA damage.[29] Secondary bile acids increase intracellular production of reactive oxygen and reactive nitrogen species resulting in increased oxidative stress and DNA damage.[30][31] As shown in the figure below, deoxycholate added to the diet of mice increased the level of 8-oxo-dG, an oxidative DNA damage, in the colonic epithelium of mice. When the level of deoxycholate-induced DNA damage is high, DNA repair enzymes that ordinarily reverse DNA damage may not be able to keep up.[citation needed]

DNA damage has frequently been proposed as a major cause of cancer.[32][33] DNA damage can give rise to cancer by causing mutations.[citation needed]

When deoxycholate was added to the food of mice so that their feces contained deoxycholate at about the same level present in feces of human on a high fat diet, 45% to 56% of the mice developed colon cancer over the next 10 months, while none of the mice on a diet without deoxycholate developed cancer.[34][35] Thus, exposure of the colon to deoxycholate may cause cancer in mice. However, this same study reported that, when chlorogenic acid was added to the diet alongside deoxycholate, only 18% of the mice developed colon cancer. Chlorogenic acid is a component of common foods and beverages; coffee contains an average of 53.8 mg chlorogenic acid per 100 ml.[36] Therefore, to consume the level of chlorogenic acid used in the study, a human on a "standard" 2000-calorie daily diet (416 g/d; 250g carbs, 100g protein, 66g fat) would need to consume roughly 55 mL of coffee each day, or just under 2 fluid ounces.

In humans, higher levels of colonic deoxycholate are associated with higher frequencies of colon cancer. As an example, the fecal deoxycholate concentrations in African Americans (who eat a relatively high fat diet) is more than five times higher than fecal deoxycholate of Native Africans in South Africa (who eat a low fat diet).[37] Male African Americans have a high incidence of colon cancer of 72 per 100,000,[38] while Native Africans in South Africa have a low incidence rate of colon cancer of less than 1 per 100,000,[39] a more than 72-fold difference in rates of colon cancer.

A prospective human study investigating the relationship between microbial metabolites and cancer found a strong correlation between circulating deoxycholic acid and colorectal cancer risk in women.[40]

Factors affecting deoxycholate levels

[

edit

]

A number of factors, including diet, obesity, and exercise, affect the level of deoxycholate in the human colon. When humans were switched from their usual diet to a meat, egg and cheese based diet for five days, deoxycholate in their feces increased by factors of 2 to 10 fold.[41] Rats fed diets with 30% beef tallow (high fat) had almost 2-fold more deoxycholate in their feces than rats fed 5% beef tallow (low fat).[42] In the same study, adding the further dietary elements of curcumin or caffeic acid to the rats' high fat (30% beef tallow) diet reduced the deoxycholate in their feces to levels comparable to levels seen in the rats on a low fat diet. Curcumin is a component of the spice turmeric, and caffeic acid is a component high in some fruits and spices.[43] Caffeic acid is also a digestive break-down product of chlorogenic acid, high in coffee and some fruits and vegetables.[44]

Colonic epithelium from a mouse not undergoing colonic tumorigenesis (A), and a mouse that is undergoing colonic tumorigenesis (B). Cell nuclei are stained dark blue with hematoxylin (for nucleic acid) and immunostained brown for 8-oxo-dG. The level of 8-oxo-dG was graded in the nuclei of colonic crypt cells on a scale of 0–4. Mice not undergoing tumorigenesis had crypt 8-oxo-dG at levels 0 to 2 (panel A shows level 1) while mice progressing to colonic tumors had 8-oxo-dG in colonic crypts at levels 3 to 4 (panel B shows level 4) Tumorigenesis was induced by adding deoxycholate to the mouse diet to give a level of deoxycholate in the mouse colon similar to the level in the colon of humans on a high fat diet.[34] The images were made from original photomicrographs.

In addition to fats, the type or amount of protein in the diet may also affect bile acid levels. Switching from a diet with protein provided by casein to a diet with protein provided by salmon protein hydrolysate led to as much as a 6-fold increase in levels of bile acids in the blood plasma of rats.[45] In humans, adding high protein to a high fat diet raised the level of deoxycholate in the plasma by almost 50%.[46]

Obesity has been linked to cancer,[47] and this link is in part through deoxycholate.[48][49][50] In obese people, the relative proportion of Firmicutes (Gram-positive bacteria) in gut microbiota is increased resulting in greater conversion of the non-genotoxic primary bile acid, cholic acid, to carcinogenic deoxycholate.[48]

Exercise decreases deoxycholate in the colon. Humans whose level of physical activity placed them in the top third had a 17% decrease in fecal bile acid concentration compared to those whose level of physical activity placed them in the lowest third.[51] Rats provided with an exercise wheel had a lower ratio of secondary bile acids to primary bile acids than sedentary rats in their feces.[52] There is a positive association of exercise and physical activity with cancer prevention, tolerance to cancer-directed therapies (radiation and chemotherapy), reduction in recurrence, and improvement in survival.[53]

References

[

edit

]

If you want to learn more, please visit our website Sodium Deoxycholate.