<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Polio vaccine and can you explain it in depth? [/INST] Polio vaccines are vaccines used to prevent poliomyelitis (polio). Two types are used: an inactivated poliovirus given by injection (IPV) and a weakened poliovirus given by mouth (OPV). The World Health Organization (WHO) recommends all children be fully vaccinated against polio. The two vaccines have eliminated polio from most of the world, and reduced the number of cases reported each year from an estimated 350,000 in 1988 to 33 in 2018.The inactivated polio vaccines are very safe. Mild redness or pain may occur at the site of injection. Oral polio vaccines cause about three cases of vaccine-associated paralytic poliomyelitis per million doses given. This compares with 5,000 cases per million who are paralysed following a polio infection. Both types of vaccine are generally safe to give during pregnancy and in those who have HIV/AIDS but are otherwise well. However, the emergence of circulating vaccine-derived poliovirus (cVDPV), a form of the vaccine virus that has reverted to causing poliomyelitis, has led to the development of novel oral polio vaccine type 2 (nOPV2) which aims to make the vaccine safer and thus stop further outbreaks of cVDPV2.The first successful demonstration of a polio vaccine was by Hilary Koprowski in 1950, with a live attenuated virus which people drank. The vaccine was not approved for use in the United States, but was used successfully elsewhere. The success of an inactivated (killed) polio vaccine, developed by Jonas Salk, was announced in 1955. Another attenuated live oral polio vaccine was developed by Albert Sabin and came into commercial use in 1961.Polio vaccine is on the World Health Organizations List of Essential Medicines.

Medical uses
Interruption of person-to-person transmission of the virus by vaccination is important in global polio eradication, since no long-term carrier state exists for poliovirus in individuals with normal immune function, polio viruses have no non-primate reservoir in nature, and survival of the virus in the environment for an extended period of time appears to be remote. There are two types of vaccine: inactivated polio vaccine (IPV) and oral polio vaccine (OPV).

Inactivated
When the IPV (injection) is used, 90% or more of individuals develop protective antibodies to all three serotypes of polio virus after two doses of inactivated polio vaccine (IPV), and at least 99% are immune to polio virus following three doses. The duration of immunity induced by IPV is not known with certainty, although a complete series is thought to provide protection for many years. IPV replaced the oral vaccine in many developed countries in the 1990s mainly due to the (small) risk of vaccine-derived polio in the oral vaccine.

Attenuated
Oral polio vaccines were easier to administer than IPV, as it eliminated the need for sterile syringes and therefore was more suitable for mass vaccination campaigns. OPV also provided longer-lasting immunity than the Salk vaccine, as it provides both humoral immunity and cell-mediated immunity.One dose of OPV produces immunity to all three poliovirus serotypes in roughly 50% of recipients. Three doses of live-attenuated OPV produce protective antibodies to all three poliovirus types in more than 95% of recipients. OPV produces excellent immunity in the intestine, the primary site of wild poliovirus entry, which helps prevent infection with wild virus in areas where the virus is endemic. The live virus used in the vaccine can rarely shed in the stool and can rarely spread to others within a community. The live virus also has stringent requirements for transport and storage, which are a problem in some hot or remote areas. As with other live-virus vaccines, immunity initiated by OPV is probably lifelong.The trivalent (against wild types 1, 2, and 3) OPV has been used to nearly eradicate polio infection worldwide. Led by the Global Polio Eradication Initiative, 155 countries switched to use the bivalent (against wild types 1 and 3) between 17 April and 1 May 2016. The bivalent OPV is more effective against types 1 and 3, but does not cover type 2. The United States as of 2017 continues to recommend the use of a trivalent version, but a fully inactivated version. The switch to the bivalent vaccine and associated missing immunity against type 2 strains, among other factors, led to outbreaks of circulating vaccine-derived poliovirus type 2(cVDPV2), which increased from 2 cases in 2016 to 1037 cases in 2020. As a response, a novel oral polio vaccine type 2 (nOPV2) was developed with the aim to provide a safer form of vaccination against type 2 strains with less risk of reverting to infectious polio.

Schedule
In countries with endemic polio or where the risk of imported cases is high, the WHO recommends OPV vaccine at birth followed by a primary series of three OPV doses and at least one IPV dose starting at 6 weeks of age, with a minimum of 4 weeks between OPV doses. In countries with >90% immunization coverage and low risk of importation, the WHO recommends one or two IPV doses starting at 2 months of age followed by at least two OPV doses, with the doses separated by 4–8 weeks depending on the risk of exposure. In countries with the highest levels of coverage and the lowest risks of importation and transmission, the WHO recommends a primary series of three IPV injections, with a booster dose after an interval of six months or more if the first dose was administered before 2 months of age.

Side effects
The inactivated polio vaccines are very safe. Mild redness or pain may occur at the site of injection. Oral polio vaccine results in vaccine-associated paralytic poliomyelitis in about three per million doses. They are generally safe to give to those who are pregnant, and those who have HIV/AIDS, but who are otherwise well.

Allergic reaction to the vaccine
Inactivated polio vaccine can cause an allergic reaction in a few people since the vaccine contains trace amounts of antibiotics, streptomycin, polymyxin B, and neomycin. It should not be given to anyone who has an allergic reaction to these medicines. Signs and symptoms of an allergic reaction, which usually appear within minutes or a few hours after receiving the injected vaccine, include breathing difficulties, weakness, hoarseness or wheezing, heart rate fluctuations, skin rash and dizziness.

Vaccine-induced polio
A potential, adverse effect of the OPV is its known ability to recombine to a form that causes neurological infection and paralysis. This genetic reversal of the pathogen to a virulent form takes a considerable time (at least 12 months) and does not affect the person who was originally vaccinated. The vaccine-derived attenuated virus is normally excreted from vaccinated people for a limited period. Thus, in areas with poor sanitation and low vaccination coverage, the spontaneous reversal of the vaccine-derived virus to a virulent form and its spreading in the environment can lead to unvaccinated people becoming infected. Clinical disease, including paralysis, caused by vaccine-derived poliovirus (VDPV) is indistinguishable from that caused by wild polioviruses. Outbreaks of vaccine-associated paralytic poliomyelitis (VAPP), caused by a circulating vaccine-derived poliovirus (cVDPV), have been reported, and tend to occur in areas of low coverage by OPV, presumably because the OPV is itself protective against the related outbreak strain. With wild polio cases at record lows, 2017 was the first year where more cases of cVDPV were recorded than the wild poliovirus, a trend that is expected to continue.To combat this, the WHO in 2016, decided to switch from the trivalent polio vaccine to the bivalent polio vaccine. This vaccine no longer contains the type 2 polio virus because it was eradicated in 1999.

Contamination concerns
In 1960, the rhesus monkey kidney cells used to prepare the poliovirus vaccines were determined to be infected with the simian virus-40 (SV40), which was also discovered in 1960 and is a naturally occurring virus that infects monkeys. In 1961, SV40 was found to cause tumors in rodents. More recently, the virus was found in certain forms of cancer in humans, for instance brain and bone tumors, pleural and peritoneal mesothelioma, and some types of non-Hodgkin lymphoma. However, SV40 has not been determined to cause these cancers.SV40 was found to be present in stocks of the injected form of the IPV in use between 1955 and 1963. It is not found in the OPV form. Over 98 million Americans received one or more doses of polio vaccine between 1955 and 1963 when a proportion of vaccine was contaminated with SV40; an estimated 10–30 million Americans may have received a dose of vaccine contaminated with SV40. Later analysis suggested that vaccines produced by the former Soviet bloc countries until 1980, and used in the USSR, China, Japan, and several African countries, may have been contaminated, meaning hundreds of millions more may have been exposed to SV40.In 1998, the National Cancer Institute undertook a large study, using cancer case information from the institutes SEER database. The published findings from the study revealed no increased incidence of cancer in persons who may have received vaccine containing SV40. Another large study in Sweden examined cancer rates of 700,000 individuals who had received potentially contaminated polio vaccine as late as 1957; the study again revealed no increased cancer incidence between persons who received polio vaccines containing SV40 and those who did not. The question of whether SV40 causes cancer in humans remains controversial, however, and the development of improved assays for detection of SV40 in human tissues will be needed to resolve the controversy.

During the race to develop an oral polio vaccine, several large-scale human trials were undertaken. By 1958, the National Institutes of Health had determined that OPV produced using the Sabin strains were the safest. Between 1957 and 1960, however, Hilary Koprowski continued to administer his vaccine around the world. In Africa, the vaccines were administered to roughly one million people in the Belgian territories (now the Democratic Republic of the Congo, Rwanda, and Burundi). The results of these human trials have been controversial, and unfounded accusations in the 1990s arose that the vaccine had created the conditions necessary for transmission of simian immunodeficiency virus from chimpanzees to humans, causing HIV/AIDS. These hypotheses, however, have been conclusively refuted. By 2004, cases of poliomyelitis in Africa had been reduced to just a small number of isolated regions in the western portion of the continent, with sporadic cases elsewhere. Recent local opposition to vaccination campaigns have evolved due to lack of adequate information, often relating to fears that the vaccine might induce sterility. The disease has since resurged in Nigeria and in several other African nations without necessary information, which epidemiologists believe is due to refusals by certain local populations to allow their children to receive the polio vaccine.

Manufacture
Inactivated
The Salk vaccine, IPV, is based on three wild, virulent reference strains, Mahoney (type 1 poliovirus), MEF-1 (type 2 poliovirus), and Saukett (type 3 poliovirus), grown in a type of monkey kidney tissue culture (Vero cell line), which are then inactivated with formalin. The injected Salk vaccine confers IgG-mediated immunity in the bloodstream, which prevents polio infection from progressing to viremia and protects the motor neurons, thus eliminating the risk of bulbar polio and post-polio syndrome.
In the United States, vaccine is administered along with the tetanus, diphtheria, and acellular pertussis vaccines (DTaP) and a pediatric dose of hepatitis B vaccine. In the UK, IPV is combined with tetanus, diphtheria, pertussis, and Haemophilus influenzae type b vaccines.

Attenuated
OPV is an attenuated vaccine, produced by the passage of the virus through nonhuman cells at a subphysiological temperature, which produces spontaneous mutations in the viral genome. Oral polio vaccines were developed by several groups, one of which was led by Albert Sabin. Other groups, led by Hilary Koprowski and H.R. Cox, developed their own attenuated vaccine strains. In 1958, the National Institutes of Health created a special committee on live polio vaccines. The various vaccines were carefully evaluated for their ability to induce immunity to polio, while retaining a low incidence of neuropathogenicity in monkeys. Large-scale clinical trials performed in the Soviet Union in late 1950s to early 1960s by Mikhail Chumakov and his colleagues demonstrated safety and high efficacy of the vaccine. Based on these results, the Sabin strains were chosen for worldwide distribution. Fifty-seven nucleotide substitutions distinguish the attenuated Sabin 1 strain from its virulent parent (the Mahoney serotype), two nucleotide substitutions attenuate the Sabin 2 strain, and 10 substitutions are involved in attenuating the Sabin 3 strain. The primary attenuating factor common to all three Sabin vaccines is a mutation located in the viruss internal ribosome entry site, which alters stem-loop structures and reduces the ability of poliovirus to translate its RNA template within the host cell. The attenuated poliovirus in the Sabin vaccine replicates very efficiently in the gut, the primary site of infection and replication, but is unable to replicate efficiently within nervous system tissue. In 1961, type 1 and 2 monovalent oral poliovirus vaccine (MOPV) was licensed, and in 1962, type 3 MOPV was licensed. In 1963, trivalent OPV (TOPV) was licensed, and became the vaccine of choice in the United States and most other countries of the world, largely replacing the inactivated polio vaccine. A second wave of mass immunizations led to a further dramatic decline in the number of polio cases. Between 1962 and 1965, about 100 million Americans (roughly 56% of the population at that time) received the Sabin vaccine. The result was a substantial reduction in the number of poliomyelitis cases, even from the much-reduced levels following the introduction of the Salk vaccine.OPV is usually provided in vials containing 10–20 doses of vaccine. A single dose of oral polio vaccine (usually two drops) contains 1,000,000 infectious units of Sabin 1 (effective against PV1), 100,000 infectious units of the Sabin 2 strain, and 600,000 infectious units of Sabin 3. The vaccine contains small traces of antibiotics—neomycin and streptomycin—but does not contain preservatives.

History
In a generic sense, vaccination works by priming the immune system with an immunogen. Stimulating immune response, by use of an infectious agent, is known as immunization. The development of immunity to polio efficiently blocks person-to-person transmission of wild poliovirus, thereby protecting both individual vaccine recipients and the wider community.The development of two polio vaccines led to the first modern mass inoculations. The last cases of paralytic poliomyelitis caused by endemic transmission of wild virus in the United States occurred in 1979, with an outbreak among the Amish in several Midwest states.

1930s
In the 1930s, poliovirus was perceived as especially terrifying, as little was known of how the disease was transmitted or how it could be prevented. This virus was also notable for primarily impacting affluent children, making it a prime target for vaccine development, despite its relatively low mortality and morbidity. Despite this, the community of researchers in the field thus far had largely observed an informal moratorium on any vaccine development as it was perceived to present too high a risk for too little likelihood of successThis shifted in the early 1930s when American groups took up the challenge: Maurice Brodie led a team from the public health laboratory of the city of New York and Dr. John A. Kolmer collaborated with the Research Institute of Cutaneous Medicine in Philadelphia. The rivalry between these two researchers lent itself to a race-like mentality which, combined with a lack of oversight of medical studies, was reflected in the methodology and outcomes of each of these early vaccine development ventures.

Kolmers live vaccine
Kolmer began his vaccine development project in 1932 and ultimately focused on producing an attenuated or live virus vaccine. Inspired by the success of vaccines for rabies and
yellow fever, he hoped to use a similar process to denature the polio virus. In order to go about attenuating his polio vaccine, he repeatedly passed the virus through monkeys. Using methods of production that were later described as "hair-raisingly amateurish, the therapeutic equivalent of bath-tub gin," Kolmer ground the spinal cords of his infected monkeys and soaked them in a salt solution. He then filtered the solution through mesh, treated it with ricinolate, and refrigerated the product for 14 days to ultimately create what would later be prominently critiqued as a "veritable witches brew".In keeping with the norms of the time, Kolmer completed a relatively small animal trial with 42 monkeys before proceeding to self experimentation in 1934. He tested his vaccine upon himself, his two children, and his assistant. He gave his vaccine to just 23 more children before declaring it safe and sending it out to doctors and health departments for a larger test of efficacy. By April 1935, he was able to report having tested the vaccine on 100 children without ill effect. Kolmers first formal presentation of results would not come about until November 1935 where he presented the results of 446 children and adults he had vaccinated with his attenuated vaccine. He also reported that together the Research Institute of Cutaneous Medicine and the Merrell Company of Cincinnati (the manufacturer who held the patent for his ricinoleating process) had distributed 12,000 doses of vaccine to some 700 physicians across the United States and Canada. Kolmer did not describe any monitoring of this experimental vaccination program nor did he provide these physicians with instructions in how to administer the vaccine or how to report side effects. Kolmer dedicated the bulk of his publications thereafter to explaining what he believed to be the cause of the 10+ reported cases of paralytic polio following vaccination, in many cases in towns where no polio outbreak had occurred. Six of these cases had been fatal. Kolmer had no control group but asserted that many more children would have gotten sick.

Brodies inactivated vaccine
At nearly the same time as Kolmers project, Maurice Brodie had joined immunologist Dr. William H. Park at the New York City Health Department where they worked together on poliovirus. With the aid of grant funding from the Presidents Birthday Ball Commission (a predecessor to what would become the March of Dimes), Brodie was able to pursue development of an inactivated or "killed virus" vaccine. Brodies process also began by grinding the spinal cords of infectious monkeys and then treating the cords with various germicides, ultimately finding a solution of formaldehyde to be the most effective. By the June 1, 1934, Brodie was able to publish his first scholarly article describing his successful induction of immunity in three monkeys with inactivated polio virus. Through continued study on an additional 26 monkeys, Brodie ultimately concluded that administration of live virus vaccine tended to result in humoral immunity while administration of killed virus vaccine tended to result in tissue immunity.Soon after, following a similar protocol to Kolmer, Brodie proceeded with self experimentation upon himself and his co-workers at the NYC Health Department laboratory. Brodies progress was eagerly covered by popular press as the public hoped for a successful vaccine to become available. Such reporting did not make mention of the 12 children in a New York City Asylum who were subjected to early safety trials. As none of the subjects experienced ill effects, Dr. Park, described by contemporaries as "never one to let grass grow under his feet," declared the vaccine safe. When a severe polio outbreak overwhelmed Kern County, California it became the first trial site for the new vaccine on very short notice. Between November 1934 - May 1935, over 1,500 doses of the vaccine were administered in Kern County. While initial results were very promising, insufficient staffing and poor protocol design left Brodie open to criticism when he published the California results in August 1935. Through private physicians, Brodie also conducted a broader field study, including 9,000 children who received the vaccine and 4,500 age- and location-matched controls who did not receive a vaccine. Again, results were promising. Of those who received the vaccine, only a few went on to develop polio. Most had been exposed prior to vaccination and none had received the full series of vaccine doses being studied. Additionally, a polio epidemic in Raleigh, North Carolina provided an opportunity for the U.S. Public Health Service to conduct a highly structured trial of the Brodie vaccine using funding from the Birthday Ball Commission.

Academic reception
While their work was ongoing, the larger community of bacteriologists began to raise concerns regarding the safety and efficacy of the new poliovirus vaccines. At this time there was very little oversight of medical studies, and ethical treatment of study participants largely relied upon moral pressure from peer academic scientists. Brodies inactivated vaccines faced scrutiny from many who felt killed virus vaccines could not be efficacious. While researchers were able to replicate the tissue immunity he had produced in his animal trials, prevailing wisdom was that humoral immunity was essential for an efficacious vaccine. Kolmer directly questioned the killed virus approach in scholarly journals. Kolmers studies however had raised even more concern with increasing reports of children becoming paralysed following vaccination with his live virus vaccine and notably, with paralysis beginning at the arm rather than the foot in many cases. Both Kolmer and Brodie were called to present their research at the Annual Meeting of the American Public Health Association in Milwaukee WI in October 1935. Additionally, Dr. Thomas M. Rivers was asked to discuss each of the presented papers as a prominent critic of the vaccine development effort. This resulted in the APHA arranging a Symposium on Poliomyelitis to be delivered at the Annual Meeting of their Southern Branch the following month. It was during the discussion at this meeting that Dr. James Leake of the U.S. Public Health Service stood to immediately present clinical evidence that the Kolmer vaccine had caused several deaths and then allegedly accused Kolmer of being a murderer. As Rivers recalled in his oral history, "All hell broke loose, and it seemed as if everybody was trying to talk at the same time....Jimmy Leake used the strongest language that I have ever heard used at a scientific meeting." In response to the attacks from all sides, Brodie was reported to have stood up and stated, "It looks as though, according to Dr. Rivers, my vaccine is no good, and, according to Dr. Leake, Dr Kolmers is dangerous." Kolmer simply responded by stating, "Gentlemen, this is one time I wish the floor would open up and swallow me." Ultimately, Kolmers live vaccine was undoubtedly shown to be dangerous and had already been withdrawn in September 1935 prior to the Milwaukee meeting. While the consensus of the symposium was largely sceptical of the efficacy of Brodies vaccine, its safety was not in question and the recommendation was for a much larger well-controlled trial. However, when three children became ill with paralytic polio following a dose of the vaccine, the directors of the Warm Springs Foundation in Georgia (acting as the primary funders for the project) requested it be withdrawn in December 1935. Following its withdrawal, the previously observed moratorium on human poliomyelitis vaccine development resumed and there would not be another attempt for nearly 20 years.While Brodie had arguably made the most progress in the pursuit of a poliovirus vaccine, he suffered the most significant career repercussions due to his status as a less widely known researcher. Modern researchers recognize that Brodie may well have developed an effective polio vaccine, however the basic science and technology of the time was insufficient to understand and utilize this breakthrough. Brodies work using formalin-inactivated virus would later become the basis for the Salk vaccine, but he would not live to see this success. Brodie was fired from his position within three months of the symposiums publication. While he was able to find another laboratory position, he died of a heart attack only three years later at age 36. By contrast, Park, who was believed in the community to be reaching senility at this point in his older age, was able to retire from his position with honors prior to his death in 1939. Kolmer, already an established and well respected researcher, returned to Temple University as a professor of medicine. Kolmer had a very productive career, receiving multiple awards, and publishing countless papers, articles, and textbooks up until his retirement in 1957.

1948
A breakthrough came in 1948 when a research group headed by John Enders at the Childrens Hospital Boston successfully cultivated the poliovirus in human tissue in the laboratory. This group had recently successfully grown mumps in cell culture. In March 1948, Thomas H. Weller was attempting to grow varicella virus in embryonic lung tissue. He had inoculated the planned number of tubes when he noticed that there were a few unused tubes. He retrieved a sample of mouse brain infected with poliovirus and added it to the remaining test tubes, on the off chance that the virus might grow. The varicella cultures failed to grow, but the polio cultures were successful. This development greatly facilitated vaccine research and ultimately allowed for the development of vaccines against polio. Enders and his colleagues, Thomas H. Weller and Frederick C. Robbins, were recognized in 1954 for their efforts with a Nobel Prize in Physiology or Medicine. Other important advances that led to the development of polio vaccines were: the identification of three poliovirus serotypes (Poliovirus type 1 – PV1, or Mahoney; PV2, Lansing; and PV3, Leon); the finding that prior to paralysis, the virus must be present in the blood; and the demonstration that administration of antibodies in the form of gamma globulin protects against paralytic polio.

1950–1955
During the early 1950s, polio rates in the U.S. were above 25,000 annually; in 1952 and 1953, the U.S. experienced an outbreak of 58,000 and 35,000 polio cases, respectively, up from a typical number of some 20,000 a year, with deaths in those years numbering 3,200 and 1,400. Amid this U.S. polio epidemic, millions of dollars were invested in finding and marketing a polio vaccine by commercial interests, including Lederle Laboratories in New York under the direction of H. R. Cox. Also working at Lederle was Polish-born virologist and immunologist Hilary Koprowski of the Wistar Institute in Philadelphia, who tested the first successful polio vaccine, in 1950. His vaccine, however, being a live attenuated virus taken orally, was still in the research stage and would not be ready for use until five years after Jonas Salks polio vaccine (a dead-virus injectable vaccine) had reached the market. Koprowskis attenuated vaccine was prepared by successive passages through the brains of Swiss albino mice. By the seventh passage, the vaccine strains could no longer infect nervous tissue or cause paralysis. After one to three further passages on rats, the vaccine was deemed safe for human use. On 27 February 1950, Koprowskis live, attenuated vaccine was tested for the first time on an 8-year-old boy living at Letchworth Village, an institution for physically and mentally disabled people located in New York. After the child had no side effects, Koprowski enlarged his experiment to include 19 other children.

Jonas Salk
The first effective polio vaccine was developed in 1952 by Jonas Salk and a team at the University of Pittsburgh that included Julius Youngner, Byron Bennett, L. James Lewis, and Lorraine Friedman, which required years of subsequent testing. Salk went on CBS radio to report a successful test on a small group of adults and children on 26 March 1953; two days later, the results were published in JAMA. Leone N. Farrell invented a key laboratory technique that enabled the mass production of the vaccine by a team she led in Toronto. Beginning 23 February 1954, the vaccine was tested at Arsenal Elementary School and the Watson Home for Children in Pittsburgh, Pennsylvania.Salks vaccine was then used in a test called the Francis Field Trial, led by Thomas Francis, the largest medical experiment in history at that time. The test began with about 4,000 children at Franklin Sherman Elementary School in McLean, Virginia, and eventually involved 1.8 million children, in 44 states from Maine to California. By the conclusion of the study, roughly 440,000 received one or more injections of the vaccine, about 210,000 children received a placebo, consisting of harmless culture media, and 1.2 million children received no vaccination and served as a control group, who would then be observed to see if any contracted polio.The results of the field trial were announced 12 April 1955 (the tenth anniversary of the death of President Franklin D. Roosevelt, whose paralytic illness was generally believed to have been caused by polio). The Salk vaccine had been 60–70% effective against PV1 (poliovirus type 1), over 90% effective against PV2 and PV3, and 94% effective against the development of bulbar polio. Soon after Salks vaccine was licensed in 1955, childrens vaccination campaigns were launched. In the U.S, following a mass immunization campaign promoted by the March of Dimes, the annual number of polio cases fell from 35,000 in 1953 to 5,600 by 1957. By 1961 only 161 cases were recorded in the United States.A week before the announcement of the Francis Field Trial results in April 1955, Pierre Lépine at the Pasteur Institute in Paris had also announced an effective polio vaccine.

Safety incidents
In April 1955, soon after mass polio vaccination began in the US, the Surgeon General began to receive reports of patients who contracted paralytic polio about a week after being vaccinated with Salk polio vaccine from the Cutter pharmaceutical company, with the paralysis limited to the limb the vaccine was injected into. The Cutter vaccine had been used in vaccinating 200,000 children in the western and midwestern United States. Later investigations showed that the Cutter vaccine had caused 40,000 cases of polio, killing 10. In response the Surgeon General pulled all polio vaccines made by Cutter Laboratories from the market, but not before 250 cases of paralytic illness had occurred. Wyeth polio vaccine was also reported to have paralyzed and killed several children.
It was soon discovered that some lots of Salk polio vaccine made by Cutter and Wyeth had not been properly inactivated, allowing live poliovirus into more than 100,000 doses of vaccine. In May 1955, the National Institutes of Health and Public Health Services established a Technical Committee on Poliomyelitis Vaccine to test and review all polio vaccine lots and advise the Public Health Service as to which lots should be released for public use. These incidents reduced public confidence in polio vaccine, leading to a drop in vaccination rates.

1961
At the same time that Salk was testing his vaccine, both Albert Sabin and Hilary Koprowski continued working on developing a vaccine using live virus. During a meeting in Stockholm to discuss polio vaccines in November 1955, Sabin presented results obtained on a group of 80 volunteers, while Koprowski read a paper detailing the findings of a trial enrolling 150 people. Sabin and Koprowski both eventually succeeded in developing vaccines. Because of the commitment to the Salk vaccine in America, Sabin and Koprowski both did their testing outside the United States, Sabin in Mexico and the Soviet Union, Koprowski in the Congo and Poland. In 1957, Sabin developed a trivalent vaccine containing attenuated strains of all three types of poliovirus. In 1959, ten million children in the Soviet Union received the Sabin oral vaccine. For this work, Sabin was given the medal of the Order of Friendship of Peoples, described as the Soviet Unions highest civilian honor. Sabins oral vaccine using live virus came into commercial use in 1961.Once Sabins oral vaccine became widely available, it supplanted Salks injected vaccine, which had been tarnished in the publics opinion by the Cutter incident of 1955, in which Salk vaccines improperly prepared by one company resulted in several children dying or becoming paralyzed.

1987
An enhanced-potency IPV was licensed in the United States in November 1987, and is currently the vaccine of choice there. The first dose of polio vaccine is given shortly after birth, usually between 1 and 2 months of age, and a second dose is given at 4 months of age. The timing of the third dose depends on the vaccine formulation, but should be given between 6 and 18 months of age. A booster vaccination is given at 4 to 6 years of age, for a total of four doses at or before school entry. In some countries, a fifth vaccination is given during adolescence. Routine vaccination of adults (18 years of age and older) in developed countries is neither necessary nor recommended because most adults are already immune and have a very small risk of exposure to wild poliovirus in their home countries. In 2002, a pentavalent (five-component) combination vaccine (called Pediarix) containing IPV was approved for use in the United States.

1988
A global effort to eradicate polio, led by the World Health Organization (WHO), UNICEF, and the Rotary Foundation, began in 1988, and has relied largely on the oral polio vaccine developed by Albert Sabin and Mikhail Chumakov (Sabin-Chumakov vaccine).

After 1990
Polio was eliminated in the Americas by 1994. The disease was officially eliminated in 36 Western Pacific countries, including China and Australia, in 2000. Europe was declared polio-free in 2002. Since January 2011, no cases of the disease have been reported in India, hence in February 2012, the country was taken off the WHO list of polio-endemic countries. In March 2014, India was declared a polio-free country.Although poliovirus transmission has been interrupted in much of the world, transmission of wild poliovirus does continue and creates an ongoing risk for the importation of wild poliovirus into previously polio-free regions. If importations of poliovirus occur, outbreaks of poliomyelitis may develop, especially in areas with low vaccination coverage and poor sanitation. As a result, high levels of vaccination coverage must be maintained. In November 2013, the WHO announced a polio outbreak in Syria. In response, the Armenian government put out a notice asking Syrian Armenians under age 15 to get the polio vaccine. As of 2014, polio virus had spread to 10 countries, mainly in Africa, Asia, and the Middle East, with Pakistan, Syria, and Cameroon advising vaccinations to outbound travellers.Polio vaccination programs have been resisted by some people in Pakistan, Afghanistan, and Nigeria - the three countries as of 2017 with remaining polio cases. Almost all Muslim religious and political leaders have endorsed the vaccine, but a fringe minority believes that the vaccines are secretly being used for sterilization of Muslims. The fact that the CIA organized a fake vaccination program in 2011 to help find Osama Bin Laden is an additional cause of distrust. In 2015, the WHO announced a deal with the Taliban to encourage them to distribute the vaccine in areas they control. However, the Pakistani Taliban was not supportive. On 11 September 2016, two unidentified gunmen associated with the Pakistani Taliban, Jamaat-ul-Ahrar, shot Zakaullah Khan, a doctor who was administering polio vaccines in Pakistan. The leader of the Jamaat-ul-Ahrar claimed responsibility for the shooting and stated that the group would continue this type of attack. Such resistance to and scepticism of vaccinations has consequently slowed down the polio eradication process within the two remaining endemic countries.

Travel requirements
Travellers who wish to enter or leave certain countries must be vaccinated against polio, usually at most 12 months and at least 4 weeks before crossing the border, and be able to present a vaccination record/certificate at the border checks.: 25–27  Most requirements apply only to travel to or from so-called polio-endemic, polio-affected, polio-exporting, polio-transmission, or high-risk countries. As of August 2020, Afghanistan and Pakistan are the only polio-endemic countries in the world (where wild polio has not yet been eradicated). Several countries have additional precautionary polio vaccination travel requirements, for example to and from key at-risk countries, which as of December 2020 include China, Indonesia, Mozambique, Myanmar, and Papua New Guinea.

Society and culture
Cost
As of 2015, the Global Alliance for Vaccines and Immunization supplies the inactivated vaccine to developing countries for as little as €0.75 (about US$0.89) per dose in 10-dose vials.

Misconceptions
A misconception has been present in Pakistan that polio vaccine contained haram ingredients and could cause impotence and infertility in male children, leading some parents not to have their children vaccinated. This belief is most common in the Khyber Pakhtunkhwa province and the FATA region. Attacks on polio vaccination teams have also occurred, thereby hampering international efforts to eradicate polio in Pakistan and globally.

References
Further reading
Ramsay M, ed. (2013). "Polio: the green book, chapter 26". Immunisation against infectious disease. London: Public Health England.
Wallace G, Alexander J (2015). "Chapter 18: Poliomyelitis".  In Hamborsky J, Kroger A, Wolfe S (eds.). Epidemiology and Prevention of Vaccine-Preventable Diseases (13th ed.). Washington D.C.: U.S. Centers for Disease Control and Prevention (CDC). ISBN 978-0990449119.
Routh JA, Oberste MS, Patel M (2018). "Chapter 12: Poliomyelitis" </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Topical steroid and can you explain it in depth? [/INST] Topical steroids are the topical forms of corticosteroids. Topical steroids are the most commonly prescribed topical medications for the treatment of rash, eczema, and dermatitis. Topical steroids have anti-inflammatory properties and are classified based on their skin vasoconstrictive abilities. There are numerous topical steroid products. All the preparations in each class have the same anti-inflammatory properties but essentially differ in base and price.
Side effects may occur from long-term topical steroid use.

Medical uses
Weaker topical steroids are utilized for thin-skinned and sensitive areas, especially areas under occlusion, such as the armpit, groin, buttock crease, and breast folds. Weaker steroids are used on the face, eyelids, diaper area, perianal skin, and intertrigo of the groin or body folds. Moderate steroids are used for atopic dermatitis, nummular eczema, xerotic eczema, lichen sclerosis et atrophicus of the vulva, scabies (after scabiecide) and severe dermatitis. Strong steroids are used for psoriasis, lichen planus, discoid lupus, chapped feet, lichen simplex chronicus, severe poison ivy exposure, alopecia areata, nummular eczema, and severe atopic dermatitis in adults.To prevent tachyphylaxis, a topical steroid is often prescribed to be used on a week on, week off routine. Some recommend using the topical steroid for 3 consecutive days on, followed by 4 consecutive days off. Long-term use of topical steroids can lead to secondary infection with fungus or bacteria (see tinea incognito), skin atrophy, telangiectasia (prominent blood vessels), skin bruising and fragility.The use of the finger tip unit may be helpful in guiding how much topical steroid is required to cover different areas of the body.

Adverse effects
Hypothalamic–pituitary–adrenal axis (HPA) suppression
Cushings syndrome
Diabetes mellitus
Osteoporosis
Topical steroid addiction
Allergic contact dermatitis (see steroid allergy)
Steroid atrophy
Perioral dermatitis: This is a rash that occurs around the mouth and the eye region that has been associated with topical steroids.
Ocular effects: Topical steroid drops are frequently used after eye surgery but can also raise intraocular pressure (IOP) and increase the risk of glaucoma, cataract, retinopathy as well as systemic adverse effects.
Tachyphylaxis: The acute development of tolerance to the action of a drug after repeated doses </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Clemastine and can you explain it in depth? [/INST] Clemastine, also known as meclastin, is a first-generation H1 histamine antagonist (antihistamine) with anticholinergic properties (drying) and sedative side effects. Like all first-generation antihistamines, it is sedating.Patented in 1960, it came into medical use in 1967.

Medical uses
Clemastine is used to relieve hay fever and allergy symptoms, including sneezing; runny nose; and red, itchy, tearing eyes. Prescription strength clemastine is also used to relieve the itching and swelling of hives.

Side effects
Overdosage symptoms are paradoxical, ranging from CNS depression to stimulation. Stimulation is most common in children, and is usually followed by excitement, hallucinations, ataxia, loss of coordination, muscle twitching, athetosis, hyperthermia, cyanosis, convulsions, tremors, and hyperreflexia. This may be followed by postictal depression and cardiovascular/respiratory arrest. Other common overdose symptoms include dry mouth, fixed dilated pupils, flushing of the face, and pyrexia </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Silver sulfadiazine and can you explain it in depth? [/INST] Silver sulfadiazine, sold under the brand Silvadene among others, is a topical antibiotic used in partial thickness and full thickness burns to prevent infection. Tentative evidence has found other antibiotics to be more effective, and therefore it is no longer generally recommended for second-degree (partial-thickness) burns, but is still widely used to protect third-degree (full-thickness) burns.Common side effects include itching and pain at the site of use. Other side effects include low white blood cell levels, allergic reactions, bluish grey discoloration of the skin, red blood cell breakdown, or liver inflammation. Caution should be used in those allergic to other sulfonamides. It should not be used in pregnant women who are close to delivery. It is not recommended for use in children less than two months of age.Silver sulfadiazine was discovered in the 1960s. It is on the World Health Organizations List of Essential Medicines. It is available as a generic medication.

Medical uses
Tentative evidence has found other antibiotics to be more effective in the healing of superficial and partial thickness burn injuries; therefore, it is no longer generally recommended. A Cochrane review from 2013 found that most of the trials that met inclusion criteria for the review had methodological shortcomings and thus are of little use in assessing the efficacy of silver sulfadiazine in the healing of burn injuries. Another Cochrane systematic review from 2010 concluded, "There is insufficient evidence to establish whether silver-containing dressings or topical agents promote wound healing or prevent wound infection". Other reviews of the evidence have also concluded, "[the] quality of the trials was limited". Cochrane has raised concerns about delays in time to wound healing when SSD is used. In addition to concerns regarding delayed wound healing, silver sulfadiazine is associated with sloughing of the wound surface that makes reassessment of wound depth difficult, and requires daily reapplication. For this reason, application of silver sulfadiazine is not recommended for most burns due to altered wound appearance and the frequency of required dressing changes.

Adverse effects
A noninfection-related clear fluid may form on the wounds surface. Burning and painful sensations are not uncommon, but are only temporary.
Application to large areas or to severe burns may lead to systemic absorption and lead to adverse effects similar to those of other sulfonamides </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Cabotegravir/rilpivirine and can you explain it in depth? [/INST] Cabotegravir/rilpivirine, sold under the brand name Cabenuva, is a co-packaged antiretroviral medication for the treatment of HIV/AIDS. It contains cabotegravir and rilpivirine in a package with two separate injection vials.The most common adverse reactions include injection site reactions, fever or feeling hot (pyrexia), fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness and rash.The co-packaged medication was approved for medical use in the United States in January 2021. It is the first FDA-approved injectable, complete regimen for HIV-infected adults that is administered once a month. It is also approved for use in Canada. In the European Union, the two medications are approved separately.

Medical uses
Cabotegravir/rilpivirine is indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults to replace a current antiretroviral regimen in those who are virologically suppressed on a stable antiretroviral regimen with no history of treatment failure. In the European Union, the combination is indicated for maintenance treatment of adults who have undetectable HIV levels in the blood (viral load less than 50 copies/mL) with their current antiretroviral treatment, and when the virus has not developed resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and integrase strand transfer inhibitors.

Contraindications and interactions
Cabotegravir/rilpivirine must not be combined with drugs that induce the liver enzyme CYP3A4, because they accelerate the inactivation of rilpivirine, and/or the enzyme UGT1A1, because they accelerate the inactivation of cabotegravir. These mechanisms potentially result in loss of effectiveness. Examples for such drugs are rifampicin, rifapentine, carbamazepine, oxcarbazepine, phenytoin and phenobarbital.

Adverse effects
The most common side effects include reactions at the injection site (in up to 84% of patients) such as pain and swelling, as well as headache (up to 12%) and fever or feeling hot (in 10%). Less common side effects (under 10%) are depressive disorders, insomnia, rashes, fatigue, musculoskeletal pain, nausea, sleep disorders, and dizziness.

Pharmacology
Cabotegravir is an integrase strand transfer inhibitor. Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI).

History
The safety and efficacy of cabotegravir/rilpivirine were established through two randomized, open-label, controlled clinical trials (Trial 1/NCT02938520 and Trial 2/NCT02951052) in 1,182 HIV-infected adults who were virologically suppressed (HIV-1 RNA less than 50 copies/milliliter) before initiation of treatment with cabotegravir/rilpivirine. Participants in both trials continued to show virologic suppression at the conclusion of each study, and no clinically relevant change from baseline in CD4+ cell counts was observed. Trials were conducted at 223 sites in 24 countries including the United States.In Trial 1, participants who were never treated for the infection before, received an approved therapy for 20 weeks. Those who did well after this treatment (who had HIV-1 RNA less than 50 copies/milliliter) were then randomized to receive either cabotegravir/rilpivirine (for the first four weeks they received tablets) or to remain on the same therapy for additional 44 weeks. Participants and the health providers knew which treatments have been given.In Trial 2, participants who were previously successfully treated for the infection (who had HIV-1 RNA less than 50 copies/milliliter), were randomized to receive either cabotegravir/rilpivirine (for the first four weeks they received tablets) or to remain on the same therapy for additional 44 weeks. Participants and the health providers knew which treatments have been given.In October 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended the granting of a marketing authorization for rilpivirine and cabotegravir, to be used together for the treatment of people with human immunodeficiency virus type 1 (HIV-1) infection </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Edex and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Zarah and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Hydroxyprogesterone caproate and can you explain it in depth? [/INST] Hydroxyprogesterone caproate (OHPC), sold under the brand names Proluton and Makena among others, is a progestin medication which is used to prevent preterm birth in pregnant women with a history of the condition and to treat gynecological disorders. It has also been formulated in combination with estrogens for various indications (brand names Gravibinon and Primosiston) and as a form of long-lasting injectable birth control (brand name Chinese Injectable No. 1). It is not used by mouth and is instead given by injection into muscle or fat, typically once per week to once per month depending on the indication.OHPC is generally well tolerated and produces few side effects. Injection site reactions such as pain and swelling are the most common side effect of OHPC. The medication may increase the risk of gestational diabetes when used in pregnant women. OHPC is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone. It has some antimineralocorticoid activity and no other important hormonal activity. The medication shows a number of differences from natural progesterone.OHPC was discovered in 1953 and was introduced for medical use in 1954 or 1955. It was marketed in the United States under the brand name Delalutin and throughout Europe under the brand name Proluton. The medication was discontinued in the United States in 1999. However, OHPC was subsequently reintroduced in the United States under the brand name Makena for the treatment of preterm birth in 2011. Due to a greatly increased price, a pricing controversy occurred in this country. OHPC was previously available at low cost from compounding pharmacies in the United States, but this became prohibited in 2016.

Medical uses
Preterm birth
The use of OHPC in pregnancy to prevent preterm birth in women with a history of preterm delivery between 20 weeks and 36 weeks and 6 days is supported by the Society of Maternal Fetal Medicine Clinic Guidelines put out in May 2012 as Level I and III evidence, Level A recommendation. Level I evidence refers to a properly powered randomized controlled trial, and level III evidence is support from expert opinion, while a Level A recommendation confers that the recommendation is made based on good and consistent scientific evidence. OHPC 250 mg IM weekly preferably starting at 16–20 weeks until 36 weeks is recommended. In these women, if the transvaginal ultrasound cervical length shortens to <25 mm at < 24 weeks, cervical cerclage may be offered. In the 2013 study the guideline recommendation is based on, there was also a significant decrease of neonatal morbidity including lower rates of necrotizing enterocolitis (0 in the treatment group vs 4 in the control), intraventricular hemorrhage (4 in the treatment group compared with 8 in the control for a relative risk of 0.25), and need for supplemental oxygen (14% in the treatment group vs 24% in the placebo for a relative risk of 0.42). Furthermore, this study contained 463 women, 310 of whom received injection. Of these women, 9 had infants with congenital malformations (2%), but there was no consistent pattern and none involved internal organs.
OHPC is currently (as of June 2014) pregnancy category B, meaning there is no evidence of fetal risk with use of this medication during pregnancy. Although this is now the recommendation, this has not always been the case. A review by Marc Keirse of Flinders University concluded that information about the potential harms was lacking. Three clinical studies in singleton pregnancies of 250 mg/week of intramuscular OHPC have all shown a trend for an increase in pregnancy loss due to miscarriage compared to placebo. One of them, a large National Institutes of Health (NIH) study in 2003, looked at the effect of OHPC injections in women at risk for repeat premature birth and found that the treated group experienced premature birth in 37% versus 55% in the controls. A follow-up study of the offspring showed no evidence that OHPC affected the children in the first years of life. Based on these NIH data, OHPC was approved by the Food and Drug Administration (FDA) in 2011 as a medication to reduce the risk of premature birth in selected women at risk. (v.i.)
The FDA expressed concern about miscarriage at the 2006 advisory committee meeting; the committee voted unanimously that further study was needed to evaluate the potential association of OHPC with increased risk of second trimester miscarriage and stillbirth. A toxicology study in rhesus monkeys resulted in the death of all rhesus fetuses exposed to 1 and 10 times the human dose equivalent of OHPC. As of 2008, OHPC was a category D progestin according to the FDA (that is, there is evidence of fetal harm). There is speculation that the castor oil in the OHPC formulation may not be beneficial for pregnancy. Of note, the above-mentioned NEJM study by Meirs et al. compares the effect of OHPC (with the castor oil component) to castor oil injection as the placebo.
A study published in February 2016 in The Lancet stated the below, amongst other findings:
OPPTIMUM strongly suggests that the efficacy of progesterone in improving outcomes is either non-existent or weak. Given the heterogeneity of the preterm labour syndrome we cannot exclude benefit in specific phenotypic or genotypic subgroups of women at risk. However, the subgroups of women who might benefit do not appear to be easily identifiable by current selection strategies, including cervical length measurement and fibronectin testing.
Reassuringly, our study suggests that progesterone is safe for those who wish to take it for preterm birth prophylaxis. The overall rate of maternal or child adverse events was similar in the progesterone and placebo groups. There were few differences in the incidence of adverse secondary outcomes in the two groups, with the exception of a higher rate of renal, gastrointestinal, and respiratory complications in childhood in the progesterone groups. Importantly, the absolute rates of these complications was low. Follow-up of other babies exposed in utero to vaginal progesterone would be helpful in determining whether the increased rate of some renal, gastrointestinal, and respiratory complications is a real effect or a type I error.
The journal reviewer Richard Lehman, senior Research Fellow at the Department of Primary Health Care at the University of Oxford, made the following notable commentary on the OPPTIMUM study: "Thats it. This story is ended, and nobody need ever use vaginal progesterone again to prevent preterm birth."A Cochrane review on progestogen for preventing preterm birth concluded that there was little evidence that either vaginal or intramuscular progesterone helped to reduce the risk of preterm birth in women with a multiple pregnancy.

Gynecological disorders
OHPC is used in the treatment of threatened miscarriage, gynecological disorders such as dysmenorrhea, premenstrual syndrome, fibrocystic breast disease, adenosis, and breast pain. In addition, OHPC is used in the treatment of endometrial cancer and has been found to be significantly effective in extending life in both premenopausal and postmenopausal women with the disease. The medication was used widely in the 1950s through the 1970s for such indications, but OHPC more recently has received the most attention in the prevention of preterm birth.

Birth control
OHPC is available in combination with estradiol valerate as a once-monthly combined injectable contraceptive in a few countries.

Other uses
OHPC has been used as a component of menopausal hormone therapy in women.OHPC has been used to treat benign prostatic hyperplasia in men, although evidence of effectiveness is marginal and uncertain. It has also been used to treat prostate cancer, at a dosage of 1,500 mg twice per week. The mechanism of action of OHPC in these uses is suppression of testicular androgen production via suppression of luteinizing hormone secretion, which are the result of the progestogenic and antigonadotropic activity of OHPC. However, symptoms of hypogonadism may develop when OHPC is used for this indication, with two-thirds of men reportedly experiencing impotence.OHPC has been used as a component of feminizing hormone therapy for transgender women. Due to micronization, bioidentical progestogens are more commonly used.

Available forms
OHPC is available alone in the form of ampoules and vials of 125 and 250 mg/mL oil solutions for intramuscular injection (brand names Proluton, Makena). It is also available alone in the form of a 250 mg/mL autoinjector for use by subcutaneous injection (brand name Makena).OHPC is or was available in combination with estradiol valerate in the form of ampoules and vials of 250 mg/mL OHPC and 5 mg/mL estradiol valerate oil solutions for intramuscular injection (brand names Gravibinon, Chinese Injectable No. 1). The medication is or was available in combination with estradiol benzoate in the form of ampoules of 125–250 mg OHPC and 10 mg estradiol benzoate in oil solution for intramuscular injection (brand name Primosiston) as well.: 1045  In addition, OHPC has been marketed in combination with estradiol dipropionate in the form of 50 mg/mL OHPC and 1 mg/mL estradiol dipropionate (brand name EP Hormone Depot) in Japan.

Contraindications
Contraindications of OHPC include previous or current thrombosis or thromboembolic disease, known or suspected breast cancer, past or present history of other hormone-sensitive cancer, undiagnosed abnormal vaginal bleeding unrelated to pregnancy, cholestatic jaundice of pregnancy, liver tumors or active liver disease, and uncontrolled hypertension. A few relative contraindications also exist for OHPC.

Side effects
OHPC is generally well tolerated and produces relatively few side effects. Injection site reactions such as pain, soreness, swelling, itching, bruising, and lumps are the most common side effect of OHPC. In contrast to large doses of progesterone however, which produce moderate-to-severe such reactions, OHPC is relatively free from injection site reactions. Side effects of OHPC that occur in greater than or equal to 2% of users include injection site pain (34.8%), injection site swelling (17.1%), urticaria (12.3%), pruritus (7.7%), injection site pruritus (5.8%), nausea (5.8%), injection site nodules (4.5%), and diarrhea (2.3%). Numerically increased rates relative to controls of miscarriage (2.4% vs. 0%), stillbirth (2.0% vs. 1.3%), admission for preterm labor (16.0% vs. 13.8%), preeclampsia or gestational hypertension (8.8% vs. 4.6%), gestational diabetes (5.6% vs. 4.6%), and oligohydramnios (3.6% vs. 1.3%) have been observed with OHPC in clinical trials in which it was given to pregnant women to prevent preterm birth.

Overdose
There have been no reports of overdose of OHPC. In the event of overdose, treatment should be based on symptoms. OHPC has been studied in humans at high doses of 2,000 to 5,000 mg per week by intramuscular injection, without safety concerns.

Interactions
OHPC is not likely to affect most cytochrome P450 enzymes at therapeutic concentrations. Drug interaction studies have not been performed with OHPC.

Pharmacology
Pharmacodynamics
OHPC has progestogenic activity, some antimineralocorticoid activity, and no other important hormonal activity.

Progestogenic activity
OHPC, also known as 17α-hydroxyprogesterone caproate, is closer to progesterone in terms of structure and pharmacology than most other progestins, and is essentially a pure progestogen – that is, a selective agonist of the progesterone receptor (PR) with minimal or no other hormonal activity. However, OHPC has improved pharmacokinetics compared to progesterone, namely a much longer duration with intramuscular injection in oil solution.Administered by intramuscular injection, the endometrial transformation dosage of OHPC per cycle is 250 to 500 mg, and the weekly substitution dosage of OHPC is 250 mg, while the effective dosage of OHPC in the menstrual delay test (Greenblatt) is 25 mg per week. An effective ovulation-inhibiting dosage of OHPC is 500 mg once per month by intramuscular injection. However, the dose of OHPC used in once-a-month combined injectable contraceptives is 250 mg, and this combination is effective for inhibition of ovulation similarly. For comparison, the dose of medroxyprogesterone acetate (MPA; 6α-methyl-17α-hydroxyprogesterone acetate), a close analogue of OHPC, used by intramuscular injection in microcrystalline aqueous suspension in once-a-month combined injectable contraceptives, is 25 mg. It has also been said that given by intramuscular injection, 250 mg OHPC in oil solution is equivalent in progestogenic potency to 50 mg medroxyprogesterone acetate in microcrystalline aqueous suspension. Although the elimination half-life of intramuscular OHPC in oil solution in non-pregnant women is about 8 days, the elimination half-life of intramuscular medroxyprogesterone acetate in microcrystalline aqueous suspension in women is around 50 days. OHPC is also to some degree less potent than the more closely related ester hydroxyprogesterone acetate (OHPA; 17α-hydroxyprogesterone acetate).17α-Hydroxyprogesterone (OHP) has weak progestogenic activity, but C17α esterification results in higher progestogenic activity. Of a variety of different esters, the caproate (hexanoate) ester was found to have the strongest progestogenic activity, and this served as the basis for the development of OHPC, as well as other caproate progestogen esters such as gestonorone caproate. OHPC is a much more potent progestogen than 17α-hydroxyprogesterone, but does not have as high of affinity for the PR as progesterone. OHPC has about 26% and 30% of the affinity of progesterone for the human PR-A and PR-B, respectively. The medication was no more efficacious than progesterone in activating these receptors and eliciting associated gene expression in vitro.

Antigonadotropic effects
Due to activation of the PR, OHPC has antigonadotropic effects, or produces suppression of the hypothalamic–pituitary–gonadal axis, and can significantly suppress gonadotropin secretion and gonadal sex hormone production at sufficiently high doses. One study found that OHPC by intramuscular injection at a dosage of 200 mg twice weekly for the first two weeks and then 200 mg once weekly for 12 weeks did not significantly influence urinary excretion of estrogens, luteinizing hormone, or follicle-stimulating hormone in men with benign prostatic hyperplasia. In another study that used an unspecified dosage of intramuscular OHPC, testosterone secretion was assessed in a single man and was found to decrease from 4.2 mg/day to 2.0 mg/day (or by approximately 52%) by 6 weeks of treatment, whereas secretion of luteinizing hormone remained unchanged in the man. Yet another study found that 3,000 mg/week OHPC by intramuscular injection suppressed testosterone levels from 640 ng/dL to 320–370 ng/dL (by 42–50%) in a single man with prostate cancer, which was similar to the testosterone suppression with cyproterone acetate or chlormadinone acetate. Gestonorone caproate, a closely related progestin to OHPC with about 5- to 10-fold greater potency in humans, was found to suppress testosterone levels by 75% at a dosage of 400 mg/week in men with prostate cancer. For comparison, orchiectomy decreased testosterone levels by 91%. In general, progestins are able to maximally suppress testosterone levels by about 70 to 80%. The antigonadotropic effects of OHPC and hence its testosterone suppression are the basis of the use of OHPC in the treatment of benign prostatic hyperplasia and prostate cancer in men. Suppression of luteinizing hormone levels by OHPC has also been observed in women.

Glucocorticoid activity
OHPC is said not to have any glucocorticoid activity. In accordance, OHPC has been found not to alter cortisol levels in humans even with very high doses by intramuscular injection. This is of relevance because medications with significant glucocorticoid activity suppress cortisol levels due to increased negative feedback on the hypothalamic–pituitary–adrenal axis. OHPC has been studied in humans at doses as high as 5,000 mg per week by intramuscular injection, with safety and without glucocorticoid effects observed. The medication does interact with the glucocorticoid receptor however; it has about 4% of the affinity of dexamethasone for the rabbit glucocorticoid receptor. But it acts as a partial agonist of the receptor and has no greater efficacy than progesterone in activating the receptor and eliciting associated gene expression in vitro.

Other activities
As a pure progestogen, OHPC has no androgenic, antiandrogenic, estrogenic, or glucocorticoid activity. The absence of androgenic and antiandrogenic activity with OHPC is in contrast to most other 17α-hydroxyprogesterone-derivative progestins. Due to its lack of androgenic properties, similarly to progesterone, OHPC does not have any teratogenic effects on the fetus, making it safe for use during pregnancy. Although OHPC has been described as a pure progestogen, there is evidence that it possesses some antimineralocorticoid activity, similarly to progesterone and 17α-hydroxyprogesterone. This includes clinically important diuretic effects and reversal of estrogen-induced fluid retention and edema. Unlike progesterone, OHPC and its metabolites are not anticipated to interact with non-genomic receptors such as membrane progesterone receptors or the GABAA receptor. In accordance, OHPC is not thought to possess the neurosteroid activities of progesterone or its associated sedative effects.In relation to cytochrome P450 enzymes, OHPC has no effect on CYP1A, CYP2D6, CYP2C9, or CYP3A4, but is a modest inducer of CYP2C19.

Differences from progesterone
There are pharmacodynamic differences between progesterone and OHPC, which may have implications for obstetrical use. These include:
Decreased myometrial activity with progesterone in vitro but no effect or increased myometrial activity with OHPC
Prevention of cervical ripening with progesterone but unknown effect with OHPC
A non-significantly increased rate of stillbirth and miscarriages with OHPC (in one study)
A possibly increased incidence of gestational diabetes with OHPC (increased in two studies, no difference in one study) but no such effect with progesterone
A significantly increased risk of perinatal adverse effects such as fetal loss and preterm delivery in multiple gestations with OHPC (in two studies)Differences in the metabolism of progesterone and OHPC and differences in the formation and activities of metabolites may be responsible for or involved in these observed biological and pharmacological differences. Progesterone is metabolized by 5α- and 5β-reductases, 3α- and 3β-hydroxysteroid dehydrogenases, and 20α- and 20β-hydroxysteroid dehydrogenase in various tissues. In target tissues, particularly the cervix and myometrium, these enzymes regulate local progesterone concentrations and can activate or inactivate progesterone signaling. In addition, these enzymes catalyze the formation of metabolites of progesterone such as 5β-dihydroprogesterone and allopregnanolone, which signal through their own non-genomic receptors such as membrane progesterone receptors and the GABAA receptor and have their own important effects in pregnancy. As examples, 5β-dihydroprogesterone has been found to play an important role in suppressing myometrial activity while allopregnanolone has potent sedative and anesthetic effects in the mother and especially the fetus and is involved in fetal nervous system development. In contrast to progesterone, OHPC is not metabolized by traditional steroid-transforming enzymes and instead is metabolized exclusively via oxidation at the caproate side chain by cytochrome P450 enzymes. As such, it is not thought to have the same tissue-specific activation and inactivation patterns that progesterone does nor the same non-genomic actions that progesterone and its metabolites possess.Further clinical research is anticipated to provide additional data to help clarify the issue of safety with OHPC. In any case, it has been recommended by the American College of Obstetricians and Gynecologists that pregnant women treated with OHPC receive counseling about its risks and benefits.

Pharmacokinetics
Absorption
In animals, the bioavailability of OHPC with intramuscular injection is nearly 100%, but its oral bioavailability is very low at less than 3%. In women, 70 mg/day oral OHPC has similar endometrial potency as 70 mg/day oral OHPA and 2.5 mg/day oral medroxyprogesterone acetate, indicating that oral OHPC and OHPA have almost 30-fold lower potency than medroxyprogesterone acetate via oral administration. Studies on progestogenic endometrial changes with oral OHPC in women are mixed however, with one finding weak effects with 100 mg/day whereas another found that doses of 250 to 1,000 mg produced no effects. As a result of its low oral potency, OHPC has not been used by the oral route and has instead been administered by intramuscular injection. However, a novel oral formulation of OHPC (developmental code name LPCN-1107) is under development and has been found to be effective, though it required administration twice a day in a clinical study.A depot effect occurs when OHPC is injected intramuscularly or subcutaneously, such that the medication has a prolonged duration of action. Following a single intramuscular injection of 1,000 mg OHPC in five women with endometrial cancer, peak levels of OHPC were 27.8 ± 5.3 ng/mL and the time to peak concentrations was 4.6 ± 1.7 (3–7) days. Following 13 weeks of continuous administration of 1,000 mg OHPC per week, trough levels of OHPC were 60.0 ± 14 ng/mL. The pharmacokinetic parameters of 250 mg OHPC once per week by intramuscular injection have also been studied in pregnant women with singleton and multiple (twin and triplet) gestation. Steady state levels of the medication are achieved within 4 to 12 weeks of administration in pregnant women. The duration of clinical biological effect of OHPC by intramuscular injection has also been studied in women. A single intramuscular injection of 65 to 500 mg OHPC in oil solution has been found to have a duration of action of 5 to 21 days in terms of effect in the uterus and on body temperature in women.OHPC has been found to possess similar pharmacokinetics, including peak levels, time to peak levels, area-under-the-curve levels (i.e., total exposure), and elimination half-life, with administration via intramuscular injection or subcutaneous autoinjection. However, there was a higher incidence of injection site pain with subcutaneous autoinjection than with intramuscular injection (37.3% vs. 8.2%).

Distribution
OHPC is extensively bound to plasma proteins, of which include albumin. Unlike progesterone and 17α-hydroxyprogesterone, OHPC has very low affinity for corticosteroid-binding globulin (less than 0.01% of that of cortisol). Progesterone and 17α-hydroxyprogesterone have low affinity for sex hormone-binding globulin, and for this reason, only a very small fraction of them (less than 0.5%) is bound to this protein in the circulation.

Metabolism
OHPC appears to be metabolized primarily by the cytochrome P450 enzymes CYP3A4 and CYP3A5. It may also be metabolized by CYP3A7 in fetal liver and the placenta. Unlike progesterone, OHPC is not metabolized by traditional steroid-transforming enzymes and does not form similar metabolites. The metabolism of OHPC is by reduction, hydroxylation, and conjugation, including glucuronidation, sulfation, and acetylation. The caproate ester of OHPC is not cleaved during metabolism, so 17α-hydroxyprogesterone is not formed from OHPC. As such, OHPC is not a prodrug of 17α-hydroxyprogesterone, nor of progesterone.OHPC has been found to have an elimination half-life of 7.8 days when given by intramuscular injection in an oil-based formulation to non-pregnant women. Its total duration is said to be 10 to 14 days, which is much longer than the duration of intramuscularly administered progesterone in an oil formulation (2 to 3 days). In pregnant women, the elimination half-life of OHPC appears to be longer, about 16 or 17 days. However, in women pregnant with twins rather than a singlet, the elimination half-life of OHPC was found to be shorter than this, at 10 days. OHPC has been detected in pregnant women up to 44 days after the last dose.

Elimination
OHPC is eliminated 50% in feces and 30% in urine when given by intramuscular injection to pregnant women. Both the free steroid and conjugates are excreted by these routes, with the conjugates more prominent in feces.

Veterinary
The pharmacokinetics of OHPC in various ungulates including cattle, buffalo, sheep, and goat have been studied.

Time–concentration curves
Chemistry
OHPC, also known as 17α-hydroxyprogesterone caproate or as 17α-hydroxypregn-4-ene-3,20-dione 17α-hexanoate, is a synthetic pregnane steroid and a derivative of progesterone. It is specifically a derivative of 17α-hydroxyprogesterone with a hexanoate (caproate) ester at the C17α position. Analogues of OHPC include other 17α-hydroxyprogesterone derivatives such as algestone acetophenide (dihydroxyprogesterone acetophenide), chlormadinone acetate, cyproterone acetate, hydroxyprogesterone acetate, hydroxyprogesterone heptanoate, medroxyprogesterone acetate, and megestrol acetate, as well as the caproate esters chlormadinone caproate, gestonorone caproate (norhydroxyprogesterone caproate), medroxyprogesterone caproate, megestrol caproate, and methenmadinone caproate.

Synthesis
Chemical syntheses of OHPC have been described.: 6

History
Along with hydroxyprogesterone acetate, OHPC was developed by Karl Junkmann of Schering AG in 1953 and was first reported by him in the medical literature in 1954. It was reportedly first marketed in Japan in 1954 or 1955, and was subsequently introduced as Delalutin in the United States in 1956. Due to its much longer duration than parenteral progesterone, OHPC had largely replaced progesterone in clinical practice by 1975. After decades of use, Squibb, the manufacturer, voluntarily withdrew the Delalutin product in the United States in 1999. Renewed interest in OHPC in the United States was sparked with a large NIH-sponsored study in 2003 that found that OHPC reduced the risk of premature birth in selected at-risk pregnant women. With follow-up data showing no evidence of harmful effects on the offspring, the FDA approved the medication, as sponsored by KV Pharmaceutical as Makena, as an orphan drug in February 2011 to reduce the risk of premature birth in women prior to 37 weeks gestation with a single fetus who had at least one previous premature birth.

Society and culture
Generic names
Hydroxyprogesterone caproate is the generic name of OHPC and its INN, USAN, BANM, and JAN, while hydroxyprogesterone hexanoate was its former BANM.OHPC is often mislabeled as and confused with progesterone and 17α-hydroxyprogesterone. It should also not be confused with hydroxyprogesterone acetate, hydroxyprogesterone heptanoate, or medroxyprogesterone acetate.

Brand names
OHPC is marketed throughout the world under a variety of brand names including Proluton, Proluton Depot, and Makena (US), among many others. It was also formerly marketed under brand names including Delalutin, Prodrox, and Hylutin among others, but these formulations have since been discontinued. It has been marketed under the brand names Gravibinon and Injectable No. 1 (or Chinese Injectable No. 1) in combination with estradiol valerate and under the brand name Primosiston in combination with estradiol benzoate.

Availability
OHPC is marketed in the United States and throughout Europe, Asia, and Central and South America. It is notably not available in Canada, the United Kingdom, New Zealand, or South Africa, and only veterinary formulations are available in Australia. OHPC is also marketed in combination with estradiol valerate as a combined injectable contraceptive in a number of countries including in South America, Mexico, Japan, and China </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Buspirone and can you explain it in depth? [/INST] Buspirone, sold under the brand name Buspar, among others, is a medication primarily used to treat anxiety disorders, particularly generalized anxiety disorder. Benefits support its short-term use. It is taken by mouth, and it may take up to four weeks to have an effect.Common side effects of buspirone include nausea, headaches, dizziness, and difficulty concentrating. Serious side effects may include hallucinations, serotonin syndrome, and seizures. Its use in pregnancy appears to be safe but has not been well studied, while use during breastfeeding is not recommended. It is a serotonin 5-HT1A receptor agonist.Buspirone was first made in 1968 and approved for medical use in the United States in 1986. It is available as a generic medication. In 2020, it was the 55th most-commonly prescribed medication in the United States, with more than 12 million prescriptions.

Medical uses
Anxiety
Buspirone is used for the short-term and long-term treatment of anxiety disorders or symptoms of anxiety. It is generally preferred over benzodiazepines because it does not activate the receptors that make drugs like alprazolam addictive.Buspirone has no immediate anxiolytic effects, and hence has a delayed onset of action; its full clinical effectiveness may require 2–4 weeks to manifest itself. The drug has been shown to be similarly effective in the treatment of generalized anxiety disorder (GAD) to benzodiazepines including diazepam, alprazolam, lorazepam, and clorazepate. Buspirone is not known to be effective in the treatment of other anxiety disorders besides GAD, although there is some limited evidence that it may be useful in the treatment of social phobia as an adjunct to selective serotonin reuptake inhibitors (SSRIs).

Other uses
Sexual dysfunction
There is some evidence that buspirone on its own may be useful in the treatment of hypoactive sexual desire disorder (HSDD) in women.

Miscellaneous
Buspirone is not effective as a treatment for benzodiazepine withdrawal, barbiturate withdrawal, or alcohol withdrawal/delirium tremens.SSRI and SNRI antidepressants such as paroxetine and venlafaxine may cause jaw pain/jaw spasm reversible syndrome (although it is not common), and buspirone appears to be successful in treating bruxism on SSRI/SNRI-induced jaw clenching.

Contraindications
Buspirone has these contraindications:
Hypersensitivity to buspirone
Metabolic acidosis, as in diabetes
Should not be used with MAO inhibitors
Severely compromised liver and/or kidney function

Side effects
Known side effects associated with buspirone include dizziness, headaches, nausea, tinnitus, and paresthesia.  Buspirone is relatively well tolerated, and is not associated with sedation, cognitive and psychomotor impairment, muscle relaxation, physical dependence, or anticonvulsant effects. In addition, buspirone does not produce euphoria and is not a drug of abuse. Dyskinesia, akathisia, myoclonus, parkinsonism, and dystonia were reported associated with buspirone. It is unclear if there is a risk of tardive dyskinesia or other movement disorders with buspirone.

Overdose
Buspirone appears to be relatively benign in cases of single-drug overdose, although no definitive data on this subject appear to be available. In one clinical trial, buspirone was administered to healthy male volunteers at a dosage of 375 mg/day, and produced side effects including nausea, vomiting, dizziness, drowsiness, miosis, and gastric distress. In early clinical trials, buspirone was given at dosages even as high as 2,400 mg/day, with akathisia, tremor, and muscle rigidity observed. Deliberate overdoses with 250 mg and up to 300 mg buspirone have resulted in drowsiness in about 50% of individuals. One death has been reported in a co-ingestion of 450 mg buspirone with alprazolam, diltiazem, alcohol, cocaine.

Interactions
Buspirone has been shown in vitro to be metabolized by the enzyme CYP3A4. This finding is consistent with the in vivo interactions observed between buspirone and these inhibitors or inducers of cytochrome P450 3A4 (CYP3A4), among others:
Itraconazole: Increased plasma level of buspirone
Rifampicin: Decreased plasma levels of buspirone
Nefazodone: Increased plasma levels of buspirone
Haloperidol: Increased plasma levels of buspirone
Carbamazepine: Decreased plasma levels of buspirone
Grapefruit: Significantly increases the plasma levels of buspirone. See grapefruit–drug interactions.
Fluvoxamine: Moderately increase plasma levels of buspirone.Elevated blood pressure has been reported when buspirone has been administered to patients taking monoamine oxidase inhibitors (MAOIs).

Pharmacology
Pharmacodynamics
Buspirone acts as an agonist of the serotonin 5-HT1A receptor with high affinity. It is a partial agonist of both presynaptic 5-HT1A receptors, which are inhibitory autoreceptors, and postsynaptic 5-HT1A receptors. It is thought that the main effects of buspirone are mediated via its interaction with the presynaptic 5-HT1A receptor, thus reducing the firing of serotonin-producing neurons. Buspirone also has lower affinities for the serotonin 5-HT2A, 5-HT2B, 5-HT2C, 5-HT6, and 5-HT7 receptors.In addition to binding to serotonin receptors, buspirone is an antagonist of the dopamine D2 receptor with weak affinity. It preferentially blocks inhibitory presynaptic D2 autoreceptors, and antagonizes postsynaptic D2 receptors only at higher doses. In accordance, buspirone has been found to increase dopaminergic neurotransmission in the nigrostriatal pathway at low doses, whereas at higher doses, postsynaptic D2 receptors are blocked and antidopaminergic effects such as hypoactivity and reduced stereotypy, though notably not catalepsy, are observed in animals. Buspirone has also been found to bind with much higher affinity to the dopamine D3 and D4 receptors, where it is similarly an antagonist.A major metabolite of buspirone, 1-(2-pyrimidinyl)piperazine (1-PP), occurs at higher circulating levels than buspirone itself and is known to act as a potent α2-adrenergic receptor antagonist. This metabolite may be responsible for the increased noradrenergic and dopaminergic activity observed with buspirone in animals. In addition, 1-PP may play an important role in the antidepressant effects of buspirone. Buspirone also has very weak and probably clinically unimportant affinity for the α1-adrenergic receptor. However, buspirone has been reported to have shown "significant and selective intrinsic efficacy" at the α1-adrenergic receptor expressed in a "tissue- and species-dependent manner".Unlike benzodiazepines, buspirone does not interact with the GABAA receptor complex.

Pharmacokinetics
Buspirone has a low oral bioavailability of 3.9% relative to intravenous injection due to extensive first-pass metabolism. The time to peak plasma levels following ingestion is 0.9 to 1.5 hours. It is reported to have an elimination half-life of 2.8 hours, although a review of 14 studies found that the mean terminal half-life ranged between 2 and 11 hours, and one study even reported a terminal half-life of 33 hours. Buspirone is metabolized primarily by CYP3A4, and prominent drug interactions with inhibitors and inducers of this enzyme have been observed. Major metabolites of buspirone include 5-hydroxybuspirone, 6-hydroxybuspirone, 8-hydroxybuspirone, and 1-PP. 6-Hydroxybuspirone has been identified as the predominant hepatic metabolite of buspirone, with plasma levels that are 40-fold greater than those of buspirone after oral administration of buspirone to humans. The metabolite is a high-affinity partial agonist of the 5-HT1A receptor (Ki = 25 nM) similarly to buspirone, and has demonstrated occupancy of the 5-HT1A receptor in vivo. As such, it is likely to play an important role in the therapeutic effects of buspirone </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Aquaphor and can you explain it in depth? [/INST] Aquaphor is a brand of over-the-counter (OTC) skin care ointments manufactured by Beiersdorf Inc., an affiliate of Beiersdorf AG. Aquaphor is offered in four product ranges:  There are two skin protectant ointments. Aquaphor Original Ointment, used as a compounding agent  and Aquaphor Advanced Therapy Healing Ointment, sold in mass retail outlets. The other product ranges include: Aquaphor Lip Repair and Lip Repair + Protect SPF 30, and Aquaphor Baby.
Aquaphor has been  available in the United States market for over 90 years. In accordance with the Food and Drug Administrations OTC Skin Protectant Monograph  Aquaphor, containing 41 percent petrolatum (or petroleum jelly), the active ingredient, temporarily protects minor cuts, scrapes, and burns; protects and helps relieve chapped or cracked skin and lips; helps protect from the drying effects of wind and cold weather.Aquaphor is used and recommended  by health care professionals for minor post-operative wounds or defects.

History
1925: Aquaphor was developed in the Beiersdorf Inc laboratories in the USA. It was trademarked that year by Herman A. Metz, president of Beiersdorf Inc at that time.
1929: Beiersdorf sold Aquaphor’s trade marks to Duke Laboratories in order to manufacture products in the country.1936: Aquaphor’s first product offering was sold to doctors, pharmacists and hospitals in 5 lb. containers.
1960: Aquaphor production was discontinued during World War II and restarted by Duke Laboratiories in 1960. One lb cans and 2 oz tubes were sold to medical professionals.1973: Beiersdorf repurchased all trademarks from Duke Laboratories.1982: Aquaphor tube was introduced and directly sold to consumers for the first time.
1991: A new formulation Aquaphor Advanced Therapy Healing Ointment was launched, an addition to the Aquaphor Original Ointment.
2003: Aquaphor Baby Healing Ointment & Gentle Wash were  introduced.
2011: Aquaphor Lip Repair was introduced
2012: Aquaphor Lip Repair + Protect SPF 30 was launched and
Aquaphor is launched globally by Beiersdorf affiliates in 25 other countries.
2013: Aquaphor achieved the Good Housekeeping Seal.

Properties and ingredients
In a study funded by Aquaphors parent company, it was found that their "Healing Ointment" product was associated with (but did not cause) decreased redness around the wound but did not in any way perform better than other products clinically.Aquaphor is not comedogenic and does not contain any fragrances, preservatives, or dyes.Unlike Vaseline (100% petrolatum), which is occlusive, Aquaphor (41% petrolatum) claims to form a semi-occlusive barrier on the skin </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Ovide and can you explain it in depth? [/INST]  </s>