Calcium hydroxyapatite in dental. How calcium hydroxyapatite is used in cosmetology

And needles, spherulites, short-columnar, obtuse-pyramidal or tabular crystals (0001) are less common. The aggregates are massive, granular to dense, also in the form of fibrous crusts.

Under p. tr. difficult to fuse around the edges. Soluble in HCl and HNO 3 .

Hydroxylapatite as a biomineral

Up to 50% by weight of bones are composed of a specific form of hydroxyapatite (known as bone). Hydroxyapatite is the main mineral component of tooth enamel and dentine (non-stoichiometric hydroxylapatite with crystals in the form of plates measuring 40x20x5 nm and the "c" axis of the crystal structure lying in the plane of the crystal). Hydroxylapatite crystals are found in small calcifications of living organisms (in the pineal gland and other organs). Also included in the composition of pathogenic biominerals (dental, salivary, kidney stones, etc.).
The creation of biomaterials based on hydroxyapatite to replace damaged bone tissue, etc., is topical. It is often used as a filler in place of amputated bone or as a coating to promote bone ingrowth into prosthetic implants (in many other phases, albeit with a similar or even identical chemical composition oh, the body reacts quite differently). It has been shown that not only the chemical composition, but also the morphology of synthetic hydroxyapatite crystals is an important characteristic that determines the body's response to foreign material (Puleo D.A., Nanci A., 1999).

Hydroxylapatite (English) APATITE-(CaOH)) - Ca 5 (PO 4) 3 (OH)

CLASSIFICATION

PHYSICAL PROPERTIES

OPTICAL PROPERTIES

CRYSTALLOGRAPHIC PROPERTIES

Translation into other languages

Mineralized tissues, which include bone tissue, dentin, cellular and acellular cement and tooth enamel, are characterized by a high content of the mineral component, the main component of which is calcium phosphate salts.

3.1. CHEMICAL COMPOSITION OF MINERALIZED TISSUES

The formation and disintegration of the mineral component in these tissues is closely related to the exchange of calcium and phosphorus in the body. In the intercellular matrix of mineralized tissues, calcium is deposited, which also performs a structural function. In cells, calcium plays the role of a second messenger in the mechanisms of intracellular signal transduction.

A feature of all mineralized tissues, with the exception of enamel and acellular cementum, is a small number of cells with long processes, and a large extracellular matrix filled with minerals. In the proteins of the matrix, crystallization centers are formed for the formation of crystals of the mineral component - apatites. Enamel and acellular cement of the teeth are formed from the ectoderm, and the remaining mineralized tissues from the stem cells of the mesoderm. Saturation with mineral compounds depends on the type of hard tissue, topographic localization within the tissue, age and environmental conditions.

All mineralized tissues differ in the content of water, mineral and organic compounds (Table 3.1).

In enamel compared to others hard tissues the highest concentration of calcium and phosphates is determined, and the amount of these minerals decreases in the direction from the surface to the enamel-dentine border. In dentin, along with calcium and phosphate ions, a fairly high concentration of magnesium and sodium is determined. The smallest amount of calcium and phosphates is present in bone tissue and cement (Table 3.2).

The composition of hard tissues of teeth and bones includes salts HPO 4 2-, or PO 4 3-. Calcium orthophosphates can be in the form of monosubstituted

Table 3.1

Percentage distribution of water, inorganic and organic substances

in mineralized tissues

Table 3.2

Chemical composition of mineralized tissues

ionic (H 2 PO 4-), disubstituted (HPO 4 2-) or phosphate ions (PO 4 3-). Pyrophosphates are found only in tartar and bone tissue. In solutions, the pyrophosphate ion has a significant effect on the crystallization of some calcium orthophosphates, which is expressed in the regulation of the size of the crystals.

Characteristics of crystals

Most phosphorus-calcium salts crystallize with the formation of crystals of different sizes and shapes, depending on the incoming elements (Table 3.3). Crystals are present not only in mineralized tissues, but are also able to form in other tissues in the form of pathological formations.

The arrangement of atoms and molecules in a crystal can be investigated using X-ray diffraction analysis of crystal lattices. As a rule, the particles are arranged symmetrically in the crystal; they are called the unit cells of the crystal. The mesh formed by the cells is called the crystal matrix. There are 7 different

Table 3.3

Crystalline formations present in various tissues

Apatites predominate in the mineralized tissues of the animal world. They have the general formula Ca 10 (PO 4) 6 X 2 where X is represented by fluorine anions or a hydroxyl group (OH -).

Hydroxyapatite (hydroxyapatite) - the main crystal of mineralized tissues; is 95-97% in tooth enamel, 70-75% in dentin and 60-70% in bone tissue. The formula of hydroxyapatite is Ca 10 (PO 4) 6 (OH) 2. In this case, the Ca/P molar ratio (calcium phosphate ratio) is 1.67. The hydroxyapatite lattice has a hexagonal structure (Fig. 3.1, A). The hydroxyl groups are arranged along the hexagonal axis, while the phosphate groups, which are larger than the calcium ions and hydroxyls, are distributed as isosceles triangles around the hexagonal axis. Between the crystals there are microspaces filled with water (Fig. 3.1, B). Hydroxyapatites are

Rice. 3.1. Hydroxyapatite:

BUT -hexagonal form of the hydroxyapatite molecule; B - location

hydroxyapatite crystals in tooth enamel.

rather stable compounds and have a very stable ionic lattice in which the ions are densely packed and held by electrostatic forces. The bond strength is directly proportional to the charge of the ions and inversely proportional to the square of the distance between them. Hydroxyapatite is electrically neutral. If the structure of hydroxyapatite contains 8 calcium ions, then the crystal acquires a negative charge. It can also be charged positively if the number of calcium ions reaches 12. Such crystals are reactive, surface electrochemical imbalance occurs and they become unstable.

Hydroxyapatites are easily exchanged with environment, as a result of which other ions may appear in their composition (Table 3.4). The most common options for ion exchange are: Ca 2+ is replaced by Sr 2+, Ba 2+, Mo 2+ cations, less often Mg 2+, Pb 2+.

Ca 2+ cations of the surface layer of crystals can for a short

time to be replaced by cations K + , Na + .

PO 4 3- exchanges with HPO 4 2-, CO 3 2-.

OH - is replaced by halogen anions Cl - , F - , I - , Br - .

The elements of the crystal lattice of apatites can exchange with the ions of the solution surrounding the crystal and change due to the ions in this solution. In living systems, this property of apatites makes them highly sensitive to the ionic composition of blood and intercellular fluid. In turn, the ionic composition of blood and intercellular fluid depends on the nature of food and water consumed. The very process of the exchange of elements of the crystal lattice proceeds in several stages at different speeds.

The exchange of ions in the crystal lattice of hydroxyapatite changes its properties, including strength, and significantly affects the size of the crystals (Fig. 3.2).

Some ions (K +, Cl -) within a few minutes by diffusion from the surrounding biological fluid enter the hydrate

Table 3.4

Substitutable and substituting ions and molecules in the composition of apatites

Rice. 3.2.Sizes of crystals of various apatites.

hydroxyapatite layer, and then also easily leave it. Other ions (Na +, F -) easily penetrate into the hydration shell and, without lingering, are embedded in the surface layers of the crystal. Penetration of ions Ca 2+ , PO 4 3- , CO 3 2- , Sr 2+ , F - into the surface of hydroxyapatite crystals from the hydrated layer occurs very slowly, within a few hours. Only a few ions: Ca 2+, PO 4 3-, CO 3 2-, Sr 2+, F - are embedded deep into the ionic lattice. This can last from several days to several months. The predominant factor determining the possibility of substitution is the size of the atom. Similarity in charges is of secondary importance. This principle of substitution is called isomorphic substitution. However, during this substitution, the overall distribution of charges over

principle: Ca 10 x (HPO 4) x (PO 4) 6 x (OH) 2 x, where 0<х<1. Потеря Ca 2+ частич- -+ но компенсируется потерей OH и частично H , присоединённых к

phosphate.

In an acidic environment, calcium ions can be replaced by protons at

scheme:

This substitution is imperfect, since the protons are many times smaller than the calcium cation.

Such a substitution leads to the destruction of the hydroxyapatite crystal in an acidic medium.

Fluorapatites Ca 10 (PO 4) 6 F 2 are the most stable of all apatites. They are widely distributed in nature and primarily as soil minerals. Fluorapatite crystals have a hexagonal shape. In an aqueous medium, the reaction of interaction of fluorine with calcium phosphates depends on the concentration of fluorine. If it is relatively low (up to 500 mg/l), then fluorapatite crystals are formed:

Fluorine sharply reduces the solubility of hydroxyapatites in an acidic environment.

At high fluorine concentrations (>2 g/l), crystals do not form:

A disease that develops with an excessive concentration of fluorine in water and soil, teeth and bones during the formation of the bone skeleton and tooth germs is called fluorosis.

Carbonate apatite contains in its composition a few percent of carbonate or bicarbonate. The process of mineralization of biological apatites is largely determined by the presence and localization of carbonate ions in the crystal lattice. Carbonate radicals CO 3 2- can replace both OH - (A-site) and PO 4 3- (B-site) in the hydroxyapatite lattice. For example, about 4% of tooth enamel apatite is made up of carbonate groups, which replace both phosphate and hydroxide ions in a ratio of 9:1, respectively. A similar situation is typical for other naturally occurring hydroxyapatites. Conventionally, the chemical formula of carbonated hydroxyapatite can be written as Ca 10 [(PO 4) 6 -x(CO 3)x][(OH) 2 -2y(CO 3)y], where X characterizes B-substitution, and at- A-substitution. For hydroxyapatite of tooth enamel x=0,039, y=0.001. Carbonate reduces the crystallinity of apatite and makes it

more amorphous and fragile. Most often, the phosphate anions of apatites are replaced by HCO 3- ions according to the scheme:

The intensity of replacement depends on the number of bicarbonates formed. Decarboxylation reactions constantly occur in the body, and the resulting CO 2 molecules interact with H 2 O molecules. HCO 3 - anions are formed in a reaction catalyzed by carbonic anhydrase and replace phosphate anions.

Carbonate apatites are more characteristic of bone tissue. In the tissues of the tooth, they are formed in the immediate vicinity of the enamel-dentin border due to the production of HCO 3 anions by odontoblasts. The formation of HCO 3- molecules is possible due to the active metabolism of the aerobic microflora of dental plaque. The resulting amount of HCO 3- in these areas may exceed PO 4 3- , which contributes to the formation of carbonate apatite in the surface layers of enamel. The accumulation of carbonate apatite over 3-4% of the total mass of hydroxyapatite increases the caries susceptibility of the enamel. With age, the amount of carbonate apatites increases.

Strontium apatite . In the crystal lattice of apatites, Sr 2+ can displace or replace vacancies for Ca 2+ .

This leads to a violation of the crystal structure. In Transbaikalia, along the banks of the small Urov River, a disease called "Urov" disease is described. It is accompanied by damage to the bone skeleton, reduction of limbs in humans and animals. In areas contaminated with radionuclides, the unfavorable value of strontium apatite for the human body is associated with the possibility of deposition of radioactive strontium.

magnesium apatite is formed when Ca 2+ is replaced by Mg 2+ ions.

Organic substances of mineralized tissues are mainly represented by proteins, as well as carbohydrates and lipids.

3.2. PROTEINS OF THE INTERCELLULAR MATRIX

MINERALIZED TISSUES OF MESENCHYMAL

ORIGIN

Proteins of mineralized tissues form the basis for the attachment of minerals and determine the processes of mineralization. A feature of all proteins of mineralized tissues is the presence of phosphoserine, glutamate, and aspartate residues, which are able to bind Ca 2+ and thus participate in the formation of apatite crystals at the initial stage. The second feature is the presence of carbohydrates and the sequence of amino acid residues arg-gli-asp in the primary structure of proteins, which ensures their binding to cells or proteins that form the extracellular matrix.

Some proteins are found in the intercellular matrix of most mineralized tissues. These are adhesion proteins, calcium-binding proteins, proteolytic enzymes, and growth factors. Other proteins with special properties are unique to a given tissue and are associated with certain processes specific to this type of tissue.

Osteonectin - glycoprotein present in large quantities in mineralized tissue. The protein is synthesized by osteoblasts, fibroblasts, odontoblasts, and in a small amount by chondrocytes and endothelial cells. The N-terminal region of osteonectin contains a large number of negatively charged amino acids. In the formed α-helix, the N-terminal region has up to 12 binding sites for Ca 2+ , which is part of hydroxyapatite. Through the carbohydrate component, osteonectin binds to type I collagen. Thus, osteonectin ensures the interaction of the matrix components. It also regulates cell proliferation and is involved in many processes during the development and maturation of mineralized tissues.

osteopontin - protein with mol. weighing ~32,000 kDa, contains several repeats rich in aspartic acid, which give osteopontin the ability to bind to hydroxyapatite crystals.

The middle part of the molecule contains the RGD (argglu-asp) sequence responsible for cell attachment. This protein plays a key role in the construction of the mineralized matrix, the interaction of cells and the matrix, and the transport of inorganic ions.

Bone sialoprotein - specific protein of mineralized tissues with a mol. weighing ~70 kDa, 50% consisting of carbohydrates (of which 12% is sialic acid). Most carbohydrates are represented by O-linked oligosaccharides, which are contained in the N-terminal region of the protein. This protein undergoes various modifications in tyrosine sulfation reactions. The bone sialoprotein contains up to 30% of phosphorylated serine residues and repeating glutamic acid sequences that are involved in Ca 2+ binding. Bone sialoprotein was found in bones, dentin, cementum, hypertrophied chondrocytes, and osteoclasts. This protein is responsible for cell attachment and is involved in matrix mineralization.

Bone acid glycoprotein-75 - protein with a mol. weighing 75 kDa, its composition is 30% homologous to osteopontin. The presence of a large number of residues of glutamic (30%), phosphoric (8%) and sialic (7%) acids ensures its ability to bind Ca 2+ . The protein is found in bone tissue, dentin and cartilaginous growth plate and is not detected in non-mineralized tissues. Bone acid glycoprotein-75 inhibits resorption processes in mineralized tissues.

Gla proteins . A distinctive feature of the Gla protein family is the presence of 7-carboxyglutamic acid residues in their primary structure. They differ in terms of mass and number of residues of 7-carboxyglutamic acid. The formation of 7-carboxyglutamic acid occurs in the process of post-translational modification to vitamin K-dependent reaction of carboxylation of glutamic acid residues. The presence of an additional carboxyl group in 7-carboxyglutamic acid ensures easy binding and release of Ca 2+ ions.

Gla proteins include osteocalcin and matrix Gla protein.

Osteocalcin (bone glutamine protein) - a protein with a mol. weighing 6 kDa. Consists of 49 amino acid residues, of which 3 are represented by 7-carboxyglutamic acid. The protein is present in the bone tissue and dentin of the tooth. Synthesized as a precursor (Fig. 3.3).

Rice. 3.3.Formation of the active form of osteocalcin.

After cleavage of the signal peptide, pro-osteocalcin is formed, which then undergoes post-translational modification. First, glutamic acid residues are oxidized, and then CO 2 molecules are added with the participation of vitamin K-dependent glutamate carboxylase (Fig. 3.4). The activity of this enzyme is reduced in the presence of warfarin, a vitamin K antagonist.

Native osteocalcin binds Ca 2+ , going to the formation of hydroxyapatite crystals. Blood plasma contains both native osteocalcin and its fragments.

Matrix Gla protein contains 5 residues of 7-carboxyglutamic acid and is able to bind to hydroxyapatite. The protein is found in the dental pulp, lungs, heart, kidneys, cartilage and appears in the early stages of bone tissue development.

Rice. 3.4.Post-translational modification of glutamic acid residues in the pro-osteocalcin molecule. A - hydroxylation of glutamic acid; B - binding of calcium ions by 7-carboxyglutamic acid.

Protein S contains residues of 7-carboxyglutamic acid and is synthesized mainly in the liver. It is determined in the bone tissue, and with its deficiency, changes in the bone skeleton are detected.

calcium hydroxyapatite

Chemical properties

Calcium hydroxyapatite is the inorganic main component of bone tissue. The bones are about half of this substance, the enamel of the teeth is 96% of Hydroxyapatite. It is a fine white or white-yellow powder. Made from sea corals Porites. The substance is chemically inert, due to which it is actively used in dentistry, surgery and traumatology. Calcium hydroxyapatite in cosmetology, it is used as a remedy for wrinkles and other age-related skin changes.

The substance is produced in the form of a paste, granules, suspension and powder, it is part of various dietary supplements.

pharmachologic effect

Osteogenic.

Pharmacodynamics and pharmacokinetics

Hydroxyapatite is biologically compatible with human tissues, is not rejected or absorbed in the body. The substance stimulates the formation of healthy bone tissue. Usually, after use, the substance is completely replaced by bone tissue.

Indications for use

Hydroxyapatite has a fairly wide range of applications:

• as a stimulant osteogenesis in plastic and maxillofacial surgery, dentistry and traumatology;
• to fill the missing elements of bone tissue, including after elimination sequesters , wounds, fractures, after plastic surgery;
• as an implant, in endoprosthetics;
• at ;
• in the form of intradermal injections to smooth wrinkles;
• as a filler for dental filling paste after cyst removal, with, after resection, with deep;
• to fill the empty space in the root canals.

Contraindications

The tool is not used for individual intolerance.

Side effects

Adverse reactions to this substance are not observed.

Instructions for use (Method and dosage)

Hydroxyapatite can be mixed with saline , ethylene glycol , oil solution . The powder is mixed in compliance with the rules of the septic tank to a pasty state. You can use the prepared medicine within 2 minutes after preparation.

Medicine in the form of granules is used to fill the pockets formed during periodontitis . The pre-prepared pocket is densely filled with granular hydroxyapatite.
The finished paste can be injected into the injured bone after removal of altered or necrotic tissues. Then it is necessary to carefully, in layers, sew up soft tissues.

Paste and suspension are used in accordance with the recommendations specified in the instructions.

In cosmetology, an aqueous solution is used, it is administered by intradermal injection.

Overdose

Data is limited.

Interaction

The drug does not interact with other drugs.

Terms of sale

Non-prescription leave.

special instructions

If necessary, you can sterilize the substance in a dry oven at a temperature of 150 degrees Celsius, 10-15 minutes. The procedure can be repeated an unlimited number of times.

Preparations containing (Analogues)

The substance is available under various brand names, such as Belost and Kergap. Included in dietary supplements: Calcimax , Elemvital with organic calcium bone strength and so on.

Here is an article and a photo that have been circulating on the Internet for some time, we read:

Oral hygiene is being revolutionized by Japanese scientist Kause Yamagashi. He invented a toothpaste that quickly and painlessly restores tooth enamel, closes holes and cracks in the teeth. And all this without the help of dentists! The composition of the paste was obtained as a result of experiments with hydroxyl apatite - the main component of teeth - and it is similar to the composition of tooth enamel.

The paste can be applied directly to the damaged area of ​​the tooth. First, the acid contained in the substance slightly dissolves the surface of the cracked enamel. After three minutes, the paste crystallizes and the artificial material is firmly integrated into the structure of natural enamel.

Tests conducted by Japanese dentists show that a tooth healed with such a paste is no different from a healthy one. The difference is not visible even under a microscope.

But what is it really?

Let's start with the fact that the picture shows black Korean Charcle paste with activated charcoal (to eliminate bad breath)

Here is what they write on one of the forums:

Recently, a series of articles about toothpaste with hydroxyapatite has flown through the Russian Internet. Photos everywhere really were black Korean paste. This prompted us to order Adguard pastes in Japan. On eBay, sellers of such pasta were quickly found with free shipping and a price of $ 15. Lied with delivery = $ 3.6
So, order 1.03 was received at the post office on 03.27. Less than a month, which I think is fast enough. The price of an analogue in Russia is 1150 rubles.
The paste came in a small package.
The packaging is beyond praise. The paste itself is lined with corrugated cardboard and wrapped in a bubble
The paste is white...
And now a little more about the paste itself and the manufacturer:

Hydroxyapatite SP-1 is a mineral of natural origin, the cell of its crystal includes two molecules.

Approximately 70% of the solid ground substance of the bone is formed by inorganic compounds, the main component of which is the inorganic mineral hydroxyapatite. Deprived of impurities, it is the main mineral in the composition of tooth enamel and dentin.

Hydroxyapatite is the main mineral of bone tissue and hard tissues of the tooth. Ceramics based on it does not cause a rejection reaction and is able to actively bind to healthy bone tissue. Due to these properties, hydroxyapatite can be successfully used in the restoration of damaged bones, as well as as part of a bioactive layer for better implant ingrowth.

Exchange reactions on the tooth surface

The whiteness of our teeth depends on the color of the dentin, also called the color of "ivory". Dentin is the calcified tissue of the tooth that forms its bulk and determines its shape. Enamel is located on top of the dentin - the hardest tissue of the body, protecting the dentin and tooth pulp from external factors. The beauty of our teeth depends on the condition of the enamel. The enamel of a healthy tooth is translucent, its color is close to the true color of ivory. When the enamel becomes covered with plaque and stains, is subjected to a sharp mechanical impact, and also as a result of an imbalance between the processes of demineralization and remineralization, the surface of the tooth becomes dull and cloudy, and the tooth itself needs professional treatment.

The main component of dentine (70%) and enamel (97%) - hydroxyapatite - is biological calcium phosphate and the third largest component of our body (after water and collagen). Human saliva, which contains a large amount of calcium ions and phosphate ions, is a kind of saturated solution of hydroxyapatite. It protects teeth by neutralizing plaque acids and replenishes the loss of minerals during demineralization.

Once sugar enters the mouth, plaque bacteria convert the sugar into acid, and the pH of the plaque drops dramatically. As long as it remains in the acidic range and the plaque fluids are undersaturated compared to the minerals in the tooth, acids produced by the bacteria diffuse through the plaque and into the tooth, leaching calcium and phosphorus from the enamel. Demineralization takes place.

Between periods of acid formation, the alkaline buffers present in saliva diffuse into the plaque and neutralize the acids present, which arrests the loss of calcium and phosphorus. Remineralization takes place.

Remineralization occurs between periods of demineralization.

Demineralization

Remineralization

Ideally, when these processes occurring on the tooth surface are in dynamic equilibrium, there is no loss of minerals. But with excessive plaque formation, decreased salivation, eating foods rich in carbohydrates, the balance is completely shifted towards demineralization. As a result, tooth decay occurs.

It is known that at the early stage of demineralization, or the "white spot" stage, the development of caries can be prevented by the timely supply of the required amount of minerals. As a result, full-fledged tooth tissues are formed, stabilizing the further development of the disease and its complications.

Innovation in the oral care market

In 1970, Sangi Co., Ltd developed a remineralizing toothpaste containing hydroxyapatite nanoparticles to meet the needs of the public. It was first launched in 1980 by Apagard and sold over 50 million tubes. Then, extensive laboratory testing of the active ingredients of the toothpaste was carried out, after which, in 1993, hydroxyapatite was approved in Japan as an anti-caries agent. It was called medical hydroxyapatite to distinguish it from other types of hydroxyapatite (dental abrasives).

The particle sizes of hydroxyapatite manufactured by Sangi were measured in nanometers (preferably 100 nm and above). In 2003, improved technology for the production of hydroxyapatite made it possible to obtain hydroxyapatite with smaller particles (20-80 nm)

Laboratory tests have demonstrated their great remineralizing ability in relation to tooth enamel. (1 nanometer = 0.000001 millimeter)

Remineralizing toothpastes and oral care products with medical nanohydroxyapatite, developed by Sangi, are divided into two main types:

Sangi first showed serious interest in hydroxyapatite after receiving a patent for its use from NASA in 1970. The third main component of our body after water and collagen, hydroxyapatite is widely used in medicine and dentistry due to its excellent biocompatibility. As a material that restores bone tissue, it is used in dentistry, orthopedics, maxillofacial surgery for bone grafting and implantation. Hydroxyapatite is also added to perfumes, cosmetics and food products, mainly to toothpastes.

To date, oral care products are the company's main source of revenue, although hydroxyapatite is included in many of their other products: nutritional supplements, cosmetic ingredients, and adsorbents for chromatographic analysis and other research.

The priority direction of their activity is product development. And for more than 30 years, Sangi has been focusing on research and development, carefully guarding its patent. They have more than 70 approved patents covering various fields of application, and about a hundred more are pending in Japan and other countries. Sangi is currently the largest producer of hydroxyapatite in the world.

The real effectiveness of all this, of course, must be looked at in practice and experience. Search the Internet, read what they write. In general, I am skeptical about all kinds of pastes, shampoos, etc. there. It often happens that this is at least safe and that’s good, and even to all the unique properties there ... Here are some more revelations for you: for example, but is it really But they say that this is also The original article is on the website InfoGlaz.rf Link to the article from which this copy is made -