NL9101149A - Preparation for medical and/or cosmetic application with placental complex as the active ingredient, method for the production thereof, and method for medical application. - Google Patents

Abstract

The invention relates to a preparation for medical and/or cosmetic application in a woman and/or that woman's baby, with placental complex as the active ingredient. In this preparation according to the invention, placental complex is a natural autologous human placental complex, which is present in the preparation in an effective quantity together with the usual additions. This quantity is generally 0.1 to 5 0/00 w/v. The preparation is usually employed as an injection liquid and as a cream. The invention also includes a method for the production of such a preparation and a method for the treatment of a woman and/or a baby of that woman against cellular degeneration, or other abnormalities, with such a preparation.

Description

Preparation for medical and / or cosmetic use with the active ingredient placental complex, method for its preparation and method for medical use.

The present invention relates to a preparation for medical and / or cosmetic use in the woman and / or the child of that woman with the active ingredient placenta complex, and to a method for the preparation of such a preparation. The invention furthermore relates to a method for medical application.

It is known that placenta (Greek: slab; slab toss; flat cake = Latin: placenta) also called afterbirth as a breeding ground for the fruit during pregnancy. Hereinafter referred to as placenta.

A placenta weighs approx. 600 g and has a diameter of 16 to 18 cm, and contains approx. 200 ml of blood, which is absorbed into a tissue like a sponge. It is a human organ with a temporary function. In addition, it is known that this placenta has extremely good blood flow throughout its function as a source of life for the unborn child and is rich in proteins such as albumin; hormones such as estrogens and other substances such as deoxyribonucleic acid and ribonucleic acid. It is also known to recover human albumin (a blood plasma substitute), gamma globulins, immunoglobulins such as IgG, IgA, IgM, amino acids and other biological agents from placentas for pharmaceutical or diagnostic applications. Extensive research into components of the placenta is still taking place every day, and new substances are still being found there every day. The extraction and fractionation technique used therein is based and modified according to E.J. Cohn, "Separation into Fractions of Protein and Lipoprotein Components", Boston, December 12, 1945 and applicable only on an industrial scale.

The substances thus found for pharmaceutical purposes are broadly indicated in congenital or acquired immunodeficiencies, congenital and acquired α- and hypo-gamma globulinaemia, cancer therapy, acute protein loss in burns, severe recurrent bacterial infections, neonatal and premature septic conditions, osteomyelitis, meningitis.

Furthermore, pharmaceutical administration takes place in severe viral infections such as viral meningoencephalitis, hepatitis infectiosa and in case of infection by the H.I.V. virus.

Placenta extracts are also used to prevent viral infections in elderly and debilitated high-risk patients, as well as in patients undergoing immunosuppressive therapy.

It is used as an immunostimulant in cancer, as an immunosuppressor for the prevention and therapy of organ transplant rejection symptoms and for the treatment of severe aplastic anemia in patients who are not eligible for bone marrow transplantation.

In addition, since the discovery and extraction of proteins of biological origin, i.e. of humans and animals, placenta complexes or derivatives thereof, have been used in cosmetics, such as regenerative creams, with the aim of improving the elasticity of the skin and cell degeneration to brake or stop.

To this end, the placental complex is applied as an exogenous factor to induce a stimulus for cell renewal, which achieves the desired skin functions, such as those normally run in young skin.

The cosmetic preparations used contain placental complexes or derivatives thereof, it being unclear whether they are of human or animal origin.

Whatever the origin, it is known that foreign substances such as proteins upon human administration can give parenteral, oral, rectal or topical anaphylactic reactions, allergic reactions, intolerance syndromes and intoxications.

The World Health Organization established through the National Biological Standards Board in 1967 the International Unit for human blood immunoglobulins G, A, and M, which is 0.8147 milligrams.

The previously outlined intolerance syndromes for these non-body proteins are also the reason for extremely low and therefore insufficient therapeutic concentrations and dosages in topical applications, while in systemic application extremely high dosing is required due to non-acceptance, i.e. non-efficacy, of the majority of foreign proteins.

In view of the previously described indications for pharmaceutical use, these preparations are mainly used in serious conditions in mainly life-threatening situations and the side effects can only be accepted.

When using "pooled" human placentas, there is a not to be underestimated risk of intolerable infectious diseases of bacterial or viral ethiology, given the extreme blood flow of the placenta.

It is known that, even with empty artis performed blood donation, storage and transfusions, the diseases mentioned so far can be transmitted to uninfected people. Which has led to the collection, storage and administration of autologous blood and blood derivatives.

In addition to the risk of infection, the problem of blood group incompatibility is also avoided and an optimal ideal tolerance arises.

Another aspect that has led to the invention is that in most countries the Constitution stipulates that everyone, subject to restrictions imposed by or pursuant to the Law, has the right to inviolability of his body, this fundamental right primarily concerns protection of the living functioning human body, but also concerns the power of control over parts or substances separated from the body.

Usually the mother is not aware of what happens with the afterbirth.

In addition, in the case of the placenta, there is an ubiquitous respect appropriate to the mother's feelings regarding pregnancy and birth.

Accordingly, the invention includes a composition for medical and / or cosmetic use in the woman and / or the child of that woman with the active ingredient placenta complex, characterized in that the placenta complex is a natural autologous human placenta complex contained in the composition is present in an effective amount in addition to the usual additives.

Surprisingly, it has been found that when a woman and / or a child of that woman is treated with a preparation containing a natural autologous human placenta complexes, the disadvantages identified above practically do not arise.

It should be noted that in the event that a child of that woman is treated, only the specific placenta associated with that child is eligible, in other words, in the case of a second child of that woman, use should be made of another placental complex, namely that from the second placenta belonging to the second child, etc.

In other words, the placenta is polyspecific for the woman in question and monospecific for the woman born to the woman.

The compositions of the invention contain the autologous human placental complex in an amount of 0.1 ° / - 5 ° / 00 w / v. and preferably in an amount of 1 ° / -3 ° / nn.

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It has been found that when the preparations according to the invention are used in injectable form, i.e. as an injection liquid, the content of the active ingredient, i.e. the autologous human placenta complex, generally amounts to about 1.00 / 0, while for topical application the active ingredient content is approx. 2.5 ° / Λ.

The compositions of the invention can be administered to women and children of those women for a longer period of time than has been the case with traditional compositions, without significant side effects. Furthermore, it has been found that when a small but effective amount of these specific body-specific placental complexes are administered in the amounts indicated above, a multiple dose, i.e. 5 ° / o placental complex, gives excellent results, being completely absorbed and tolerated without any problem.

Due to the simplified extraction method, as mentioned in the examples, of the body's own material, the complete placenta, all high-quality low-molecular compounds for autotherapy are also retained, which is not the case with the extraction and fractionation method according to Cohn.

The autologous human placental complexes useful in the practical application of this invention can be administered topically to the donor or her child in the form of a cream. Systemic administration of the composition of the invention can be carried out in parenteral or oral, sublingual and rectal form. When administered parenterally, the autologous human placenta complex in an aqueous solution can be satisfactorily applied by subcutaneous, intramuscular or intravenous injection.

However, best results are achieved with topical application in any dosage form or vehicle, such as creams, ointments, emulsions, lotions, hair lotion, patches, etc.

Furthermore, it has been found that satisfactory results are obtained with the use of these compositions according to the invention when a concentration of 0.1 ° / to about 5 ° / wt / vol is used. of the autologous human placental complex.

In general, excellent results are obtained as a concentration of 0.5 ° / o to 2.5 ° / 00 w / v. of the autologous human placental complex is used, however, other concentrations also give satisfactory results.

The use of the preparations has been found to be successful if the preparation is administered to the donor and / or child to be treated by a dosing schedule involving topical application to the skin, whether or not under occlusion, every evening for at least 6 to 12 weeks and then 3 times a week until the desired result is achieved.

It will be understood that the dosage amount as well as the dosing schedule for topical application of the autologous human placenta complexes may vary depending on the health condition and absorption capacity of the skin and the results obtained.

In the event that injections into the bloodstream are given upon systemic administration of the autologous human placental complex, the preparation is, in principle, administered at body temperature and slowly intravenously as a drip.

Generally, immunocomplexes such as the present placental complex of autologous origin are administered every 2 or 3 weeks, the number and concentration depending on the laboratory data obtained.

In the systemic application outlined above, a buffered saline can be used.

For example, a buffered aqueous saline can be prepared using salts such as NaCl or KCl, but also with buffering agents such as Na2HPO4 or KH2PO4 to achieve a pH range of between 5 and 9, as is the case with empty artis.

The present invention is now further illustrated by the following examples. It is noted that the invention is by no means limited to the examples below.

EXAMPLE I

Extraction of autologous human placenta complex for systemic use.

Homogenize the tissue, for example by cutting and grinding in a blender for approx. 2 min., Followed by grinding with sharp sand or carborundum in a mortar. Then extract the mass with a neutral 0.1 M phosphate or borate buffer, at 4 ° C, filter over cheesecloth or filter paper, followed by cold centrifugation at 6,000-20,000 rpm. Saturate the supernatant to 50% with ammonium sulfate, centrifuge the precipitate after 1 day of cooling, dissolve in little phosphate buffer, and dialyze for 48 hours against fresh physiologically modified salt as outside fluid (nominal cut-off dialysis membrane: 10,000 Daltons). Finally, the dialyzed inner liquid is freeze-drying. The yield is about 100 mg per 100 g of wet tissue. However, by weighing the lyophilizate, it is easy to set the WHO standard. The lyophilisate can be dissolved in the phosphate buffer saline of Example III.

All final solutions are sterilized by sterile filtration through a Millipore 0.2 μ membrane filter.

EXAMPLE II

Extraction of autologous human placenta complex for topical application.

Homogenize the tissue, for example by cutting and grinding in a blender for approx. 2 min., Followed by grinding with sharp sand or carborundum in a mortar. Then extract the mass with a neutral 0.1 M phosphate or borate buffer, at 4 ° C, filter over cheesecloth or filter paper, followed by cold centrifugation at 6,000-20,000 rpm. Alcohol is added (not necessarily cooled) to 25% by volume to this extract. After 1 day, it is filtered and centrifuged. The precipitate is discarded, the supernatant is evaporated to a small volume and immediately freeze-dried. The solution to be freeze-dried must be clear, any precipitates which may appear during evaporation must be filtered or centrifuged and removed. The lyophilized preparation is weighable and contains a crude and unfractionated extract of all low molecular weight compounds. The yield, depending on the weight and blood content of the specific placenta, is about 10% lyophilisate which can be dissolved in demineralized water for processing in Example IV and sterilized by sterile filtration through a Millipore 0.2 µ membrane filter.

EXAMPLE III

A 1 ° / solution of autologous human placenta complex was prepared in phosphate buffer saline containing 1 ° / sodium alginate as described below. The following salts were dissolved in the indicated amounts in 125 ml of distilled water.

SALT QUANTITY in Mo.

NaCl 1.0 KCl 0.025

Na2HPO4 0.176 KH2PO4 0.02

1.25 mg of sodium alginate was added to this solution with stirring until completely dissolved. Then, 1.25 mg of the autologous human placenta complex was added to the solution thus obtained and stirred until completely dissolved. The solution thus obtained was then filtered, sterilized by the sterile filtration described previously, filled into a vial and stored cool until use.

EXAMPLE IV

A 2.5% autologous human placenta complex containing ivory glossy food cream was prepared as described below.

NAME QUANTITY (%) Supplier A.

TEPHOSIS 1500 8.00 Gattefossé STEARIC ACID 2.00 ISOSTEARYL ISOSTEATOR 6.00 Gattefossé VEGETABLE OIL, MARIGOLD WL 1072 4.00 Gattefossé B.

DEMINERALIZED WATER 77.6 CARBOPOL 934 0.30 Goodrich

Furthermore: TRIETHANOLAMINE, 99% (50% sol.) 0.60 Preservative, GD700 0.30 Phytocos PERFUME REF. 4968 0.20 Gattefossé AUTOGRAPHIC HUMAN PLACENTA COMPLEX 2.5 mg Dissolved in demineralised water 10 100

EMULGATE

First, the Carbopol was dissolved in the demineralized water, which was heated to 75 ° C.

The water phase B was then added to the fat phase A, which has now been heated to 75 ° C.

Then the T.E.A. solution and the whole was cooled with continuous stirring.

Then, between 30 and 35 ° C, the preservative and perfume were added, as well as 2.5 mg of autologous human placenta complex, dissolved in 10% (of the total amount of this example) of demineralized water under cooling.

As a control, a pH of approx. 6.9 applies.

Claims (7)

Preparation for medical and / or cosmetic use in the woman and / or the child of that woman with the active ingredient placental complex, characterized in that the placental complex is a natural autologous human placental complex, which in addition to the usual additives in the preparation an effective amount is present. The preparation according to claim 1, characterized in that the preparation comprises the autologous human placental complex in an amount of 0.1 to 5 ° / 00 w / v. contains. Preparation according to claim 2, characterized in that the preparation contains 1 to 3% autologous human placenta complex. Preparation according to claims 1-3, characterized in that the preparation is an injection liquid containing approximately 1.0 ° / o autologous human placenta complex. Preparation according to claims 1-3, characterized in that the preparation is a cream containing approximately 2.5 ° / 00 autologous human placenta complex. Process for the preparation of a preparation according to claims 1 to 5, characterized in that an effective amount of a natural autologous placenta complex is brought together with conventional auxiliary substances in a dosage form suitable for medical and / or cosmetic purposes. Method for the treatment of a woman and / or a child of that woman against cell degeneration or other abnormalities, characterized in that a preparation according to the preceding claims 1-5 is administered in an effective dose.